Inborn Metabolic Diseases: Diagnosis and Treatment

Preface
Contents
Editors
Contributors
Editors and Contributors
I: Diagnosis and Treatment: General Principles
	1: Clinical Approach to Inborn Errors of Metabolism in Paediatrics
		1.1	 Simplified Classification of IEM in 3 Groups
			1.1.1 Group 1. Small Molecule Disorders (7 Chaps. 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,
				1.1.1.1 Accumulation of Small Molecules
				1.1.1.2 Deficiency of Small Molecules
			1.1.2 Group 2. Complex Molecule Disorders (7 Chaps. 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44)
				1.1.2.1 Accumulation of Complex Molecules
				1.1.2.2 Deficiency of Complex Molecules
				1.1.2.3 Cellular Trafficking and Processing Disorders (7 Chap. 44)
			1.1.3 Group 3: Disorders Involving Energy Metabolism (7 Chaps. 5, 6, 7, 8, 9, 10, 11, 12, and 13)
				1.1.3.1 Membrane Carriers of Energetic Molecules
				1.1.3.2 Mitochondrial Defects
				1.1.3.3 Cytoplasmic Energy Defects
			1.1.4 Clinical Approach
		1.2	 Antenatal and Congenital Presentations
			1.2.1 Classification of Antenatal Manifestations in Three Major Clinical Categories
			1.2.2 Clinical Circumstances of Presentations
		1.3	 Presentation in Neonates and Infants (<1 Year)
			1.3.1 Neurological Deterioration (Coma, Lethargy): Metabolic Encephalopathy
			1.3.2 Seizures
				1.3.2.1 Treatable and Potentially Treatable Disorders
				1.3.2.2 Disorders without Specific Treatment
			1.3.3 Hypotonia
			1.3.4 Other Severe Motor Dysfunctions
			1.3.5 Hepatic Presentations
				1.3.5.1 Hepatomegaly with Hypoglycaemia
				1.3.5.2 Liver Failure
				1.3.5.3 Cholestatic Jaundice
				1.3.5.4 Liver Steatosis
				1.3.5.5 Hepatosplenomegaly with Storage Signs
				1.3.5.6 Hepatosplenomegaly with Inflammatory Syndrome
			1.3.6 Congenital Diarrhoeal Disorders (CDD)
			1.3.7 Cardiac and Vascular Presentations (See Also Later Presentations 1.4.8)
				1.3.7.1 Cardiomyopathies
				1.3.7.2 Arrhythmias and Conduction Defects
				1.3.7.3 Widespread Arterial Calcification
			1.3.8 Neonatal Onset Multisystemic, Chronic Inflammation Disease (NOMID)
			1.3.9 Initial Approach and Protocol for Investigation at the Bedside
			1.3.10 According to this Bedside Protocol Most Patients with Neurological Findings Can Be Classified into One of Six Metabolic Types (. Table 1.4)
				1.3.10.1 With First Line Metabolic Disturbances
				1.3.10.2 Without First Line Metabolic Disturbance (Type VI; . Table 1.5)
		1.4	 Later Onset Emergencies: Acute and Recurrent Attacks (Early Childhood and Beyond)
			1.4.1 Coma, Strokes and Attacks of Vomiting with Lethargy (. Table 1.6)
				1.4.1.1 Metabolic Coma without Focal Neurological Signs
				1.4.1.2 Neurological Coma with Focal Signs, Seizures, Severe Intracranial Hypertension, Strokes or Stroke-Like Episodes
			1.4.2 Recurrent Attacks of Ataxia (. Table 1.7) for Adult Presentations See 7 Chap. 2
			1.4.3 Acute Psychiatric Symptoms (. Table 1.8) for Adult Presentations See 7 Chap. 2
			1.4.4 Dehydration (. Table 1.9)
			1.4.5 Reye Syndrome, Sudden Unexpected Death in Infancy (SUDI) and Near-Miss
			1.4.6 Exercise Intolerance and Rhabdomyolysis (Recurrent Myoglobinuria) (See Also 7 Sect. 2.3.10 Adult Presentations)
				1.4.6.1 Glycolytic Disorders
				1.4.6.2 FAO Disorders
				1.4.6.3 Complex Molecules Disorders
				1.4.6.4 Other Causes
			1.4.7 Abdominal Pain (Recurrent Attacks)
			1.4.8 Cardiac Failure, Cardiac Arrhythmias and Cardiomyopathy (. Tables 1.11 and 1.12)
				1.4.8.1 Hypertrophic Cardiomyopathy
				1.4.8.2 Dilated Cardiomyopathy
				1.4.8.3 Arrhytmias and Conduction
			1.4.9 Liver Failure, Ascites, Oedema
			1.4.10 Pain in Extremities and Bone Crisis
			1.4.11 Metabolic Derangements and Diagnostic Tests
			1.4.12 Metabolic Acidosis (. Fig. 1.2)
			1.4.13 Ketosis (. Fig. 1.3)
			1.4.14 Hyperlactataemia
			1.4.15 Hypoglycaemia
			1.4.16 Hyperammonaemia
			1.4.17 Hyperuricaemias and Hypouricaemias
			1.4.18 Isolated Elevated Transaminases
			1.4.19 Glucosuria
		1.5	 Chronic and Progressive Neurological Symptoms (Mental Retardation, Developmental Delay, Epilepsy, Neurological Deterioration and Psychiatric Symptoms)
			1.5.1 Infants (Before 1 year)
				1.5.1.1 Category 1: Neurological Diseases Associated with Extraneurological Symptoms (. Table 1.14)
				1.5.1.2 Category 2: Disorders with Specific or Suggestive Neurological Signs (. Table 1.15)
				1.5.1.3 Category 3: Disorders with Non-Specific Developmental Delay (. Table 1.15)
			1.5.2 Early Childhood to Adolescence (>1 year to 18 years)
				1.5.2.1 Category 1: With Visceral, Craniovertebral, Ocular, or Other Somatic Abnormalities (. Table 1.16)
				1.5.2.2 Category 2: With Predominant Epilepsy (. Tables 1.17 and 1.18)
				1.5.2.3 Category 3: With Predominant Abnormal Movements: Ataxia, Hyper and Hypokinetic Movements (. Table 1.19)
				1.5.2.4 Category 4: With Complex Motor Disorders: Ataxic-Spastic Gait, Predominant Spasticity, and/or Peripheral Nerve/Motor Neuron Involvement [. Table 1.20, . Fig. 1.9 (Spasticity) and . Fig. 1.10 (Peripheral Neuropathy/Motor Neuron Diseases)]
				1.5.2.5 Category 5: With Predominant Intellectual Disability and/or Behavioural, Neuropsyhiatric Manifestations (Algorithm)
				1.5.2.6 Category 6: With Neuroregression
			1.5.3 Onset in Adulthood (>15 years to >70 years)
			1.5.4 Deafness
			1.5.5 Head Circumference, Cephalhematomas, Subdural Hematomas (. Table 1.22)
			1.5.6 Neuroimaging Signs
			1.5.7 Neuro-ophthalmological Signs (. Tables 1.28 and 1.29)
			1.5.8 Neurophysiological Signs
			1.5.9 Recommended Laboratory Tests in Neurological Syndromes
		1.6	 Specific Organ Signs and Symptoms
			1.6.1 Cardiology
			1.6.2 Dermatology
			1.6.3 Endocrinology (. Table 1.35)
			1.6.4 Gastroenterology and Nutritional Findings
			1.6.5 Haematology
			1.6.6 Hepatology
			1.6.7 Immunology (See Also Neutropenia . Table 1.38)
			1.6.8 Myology
			1.6.9 Nephrology (. Table 1.40)
			1.6.10 Neurology and Psychiatry
			1.6.11 Ophthalmologic Signs
			1.6.12 Orthopaedic Signs (. Table 1.43)
			1.6.13 Pneumology
			1.6.14 Psychiatry
			1.6.15 Rheumatology
			1.6.16 Stomatology
		References
	2: Inborn Errors of Metabolism in Adults: A Diagnostic Approach to Neurological and Psychiatric Presentations
		2.1	 Differences Between Paediatric and Adult Phenotypes
		2.2	 General Approach to IEM in Adulthood
			2.2.1	 Accumulation of Small Molecules
			2.2.2	 Deficiency of Small Molecules
			2.2.3	 Accumulation of Complex Molecules
			2.2.4	 Deficiency of Complex Molecules
			2.2.5	 Disorders of Energy Metabolism
		2.3	 Specific Approaches to Neurometabolic Presentations in Adults
			2.3.1	 Encephalopathies/Comas
			2.3.2	 Strokes and Pseudo-Strokes
			2.3.3	 Movement Disorders
			2.3.4	 Peripheral Neuropathies
			2.3.5	 Leukoencephalopathies
			2.3.6	 Epilepsy
			2.3.7	 Psychiatric Disorders
			2.3.8	 Spastic Paraparesis
			2.3.9	 Cerebellar Ataxia
			2.3.10	 Myopathy
			2.3.11	 Sensorial Disorders
		References
	3: Diagnostic Procedures
		3.1	 Basal Metabolic Investigation
			3.1.1	 Amino and Organic Acids
			3.1.2	 Metabolic Profile over the Course of the Day
		3.2	 Functional Tests
			3.2.1	 Fasting Test
			3.2.2	 Oral Glucose Loading Test
			3.2.3	 Glucagon Test
			3.2.4	 Exercise Test
		3.3	 Metabolomic Analyses for Diagnosis of IEM
		3.4	 Next Generation Sequencing and Gene Panels
		3.5	 Postmortem Protocol
			3.5.1	 Cells and Tissues for Enzyme Assays
			3.5.2	 Cells and Tissues for Chromosome and DNA Investigations
			3.5.3	 Skin Fibroblasts
			3.5.4	 Body Fluids for Chemical Investigations
			3.5.5	 Autopsy
		References
	4: Emergency Treatments
		4.1	 General Principles
			4.1.1	 Supportive Care
			4.1.2	 Nutrition
			4.1.3	 Specific Therapies
			4.1.4	 Extracorporeal Procedures for Toxin Removal
		4.2	 Emergency Management of Particular Clinical Presentations
			4.2.1	 Neurological Deterioration
				4.2.1.1	 Supportive Care
				4.2.1.2	 Nutrition
				4.2.1.3	 Specific Therapies
				4.2.1.4	 Assessment of Biochemical Progress
			4.2.2	 Liver Failure
			4.2.3	 Neonatal Hypoglycaemia
			4.2.4	 Cardiac Failure
			4.2.5	 Primary Hyperlactataemia
			4.2.6	 Intractable Seizures
		4.3	 Final Considerations
		References
II: Disorders of Energy Metabolism
	5: The Glycogen Storage Diseases and Related Disorders
		5.1	 Hepatic Glycogenoses
			5.1.1	 Glycogen Synthase 2 Deficiency (GSD 0a)
			5.1.2	 Glycogen Storage Disease Type I (GSD I)
			5.1.3	 Glycogen Storage Disease Type III (GSD III)
			5.1.4	 Glycogen Storage Disease Type IV (GSD IV)
			5.1.5	 Glycogen Storage Disease Type VI (GSD VI)
			5.1.6	 Glycogen Storage Disease Type IX (GSD IX)
			5.1.7	 Fanconi-Bickel Syndrome
		5.2	 Muscle and Cardiac Glycogenoses
			5.2.1	 Glycogen Storage Disease Type V (Myophosphorylase Deficiency, McArdle Disease)
			5.2.2	 Disorders of Glycolysis
			5.2.3	 Glycogen Storage Disease Type II (Pompe Disease)
			5.2.4	 Danon Disease (LAMP-2 Deficiency)
			5.2.5	 Glycogen Depletion Syndromes: Muscle Glycogen Synthase Deficiency (Muscle GSD Type 0, GSD 0b) and Glycogenin 1 Deficiency
			5.2.6	 Muscle and Cardiac Glycogenosis with Polyglucosan Bodies Due to RBCK1 and GYG1 Mutations
			5.2.7	 AMP-Activated Protein Kinase (AMPK) Deficiency
		5.3	 Brain Glycogenoses
			5.3.1	 Lafora Disease (Neuronal Laforin/Malin Defects)
			5.3.2	 Adult Polyglucosan Body Disease
		References
	6: Congenital Hyperinsulinism and Genetic Disorders of Insulin Resistance and Signalling
		6.1	 Clinical Presentation
		6.2	 Metabolic Derangement
		6.3	 Genetics
		6.4	 Diagnostic Tests
		6.5	 Treatment
		6.6	 Prognosis
		References
	7: Disorders of Glycolysis and the Pentose Phosphate Pathway
		7.1 Muscle Phosphofructokinase (PFKM) Deficiency
			7.1.1	 Clinical Presentation
			7.1.2	 Metabolic Derangement
			7.1.3	 Genetics
			7.1.4	 Diagnostic Tests
			7.1.5	 Treatment and Prognosis
		7.2 Aldolase A (ALDOA) Deficiency
			7.2.1	 Clinical Presentation
			7.2.2	 Metabolic Derangement
			7.2.3	 Genetics
			7.2.4	 Diagnostic Tests
			7.2.5	 Treatment and Prognosis
		7.3 Triosephosphate Isomerase (TPI) Deficiency
			7.3.1	 Clinical Presentation
			7.3.2	 Metabolic Derangement
			7.3.3	 Genetics
			7.3.4	 Diagnostic Tests
			7.3.5	 Treatment and Prognosis
		7.4 Phosphoglycerate Kinase (PGK) Deficiency
			7.4.1	 Clinical Presentation
			7.4.2	 Metabolic Derangement
			7.4.3	 Genetics
			7.4.4	 Diagnostic Tests
			7.4.5	 Treatment and Prognosis
		7.5 Phosphoglycerate Mutase (PGAM) Deficiency
			7.5.1	 Clinical Presentation
			7.5.2	 Metabolic Derangement
			7.5.3	 Genetics
			7.5.4	 Diagnostic Tests
			7.5.5	 Treatment and Prognosis
		7.6 Enolase Deficiency
			7.6.1	 Clinical Presentation
			7.6.2	 Metabolic Derangement
			7.6.3	 Genetics
			7.6.4	 Diagnostic Tests
			7.6.5	 Treatment and Prognosis
		7.7 Lactate Dehydrogenase (LDH) Deficiency
			7.7.1	 Clinical Presentation
			7.7.2	 Metabolic Derangement
			7.7.3	 Genetics
			7.7.4	 Diagnostic Tests
			7.7.5	 Treatment and Prognosis
		7.8 Glycerol Kinase Deficiency (GKD)
			7.8.1	 Clinical Presentation
			7.8.2	 Metabolic Derangement
			7.8.3	 Genetics
			7.8.4	 Diagnostic Tests
			7.8.5	 Treatment and Prognosis
		7.9 Ribose-5-Phosphate Isomerase (RPI) Deficiency
			7.9.1	 Clinical Presentation
			7.9.2	 Metabolic Derangement
			7.9.3	 Genetics
			7.9.4	 Diagnostic Tests
			7.9.5	 Treatment and Prognosis
		7.10 Transaldolase (TALDO) Deficiency
			7.10.1	 Clinical Presentation
			7.10.2	 Metabolic Derangement
			7.10.3	 Genetics
			7.10.4	 Diagnostic Tests
			7.10.5	 Treatment and Prognosis
		7.11 Transketolase (TKT) Deficiency
			7.11.1	 Clinical Presentation
			7.11.2	 Metabolic Derangement
			7.11.3	 Genetics
			7.11.4	 Diagnostic Tests
			7.11.5	 Treatment and Prognosis
		7.12 Sedoheptulokinase (SHPK) Deficiency
			7.12.1	 Clinical Presentation
			7.12.2	 Metabolic Derangement
			7.12.3	 Genetics
			7.12.4	 Diagnostic Tests
			7.12.5	 Treatment and Prognosis
		References
	8: Disorders of Glucose and Monocarboxylate Transporters
		8.1 Congenital Glucose/Galactose Malabsorption (SGLT1 Deficiency)
			8.1.1 Clinical Presentation
			8.1.2 Metabolic Derangement
			8.1.3 Genetics
			8.1.4 Diagnostic Tests
			8.1.5 Treatment and Prognosis
		8.2 Renal Glucosuria (SGLT2 Deficiency)
			8.2.1 Clinical Presentation
			8.2.2 Metabolic Derangement
			8.2.3 Genetics
			8.2.4 Diagnostic Tests
			8.2.5 Treatment and Prognosis
		8.3 Glucose Transporter-1 Deficiency Syndrome (GLUT1DS)
			8.3.1 Clinical Presentation
			8.3.2 Metabolic Derangement
			8.3.3 Genetics
			8.3.4 Diagnostic Tests
			8.3.5 Treatment and Prognosis
		8.4 Intellectual Developmental Disorder with Neuropsychiatric Features (PAST-A Deficiency)
			8.4.1 Clinical Presentation
			8.4.2 Metabolic Derangement
			8.4.3 Genetics
			8.4.4 Diagnostic Tests
			8.4.5 Treatment and Prognosis
		8.5 Fanconi-Bickel Syndrome (GLUT2 Deficiency)
			8.5.1 Clinical Presentation
			8.5.2 Metabolic Derangement
			8.5.3 Genetics
			8.5.4 Diagnostic Tests
			8.5.5 Treatment and Prognosis
		8.6 Other Defects of Glucose Transporters
		8.7 Monocarboxylate Transporter-1 Deficiency (MCT1 Deficiency)
			8.7.1 Clinical Presentation
			8.7.2 Metabolic Derangement
			8.7.3 Genetics
			8.7.4 Diagnostic Tests
			8.7.5 Treatment and Prognosis
		8.8 Exercise-Induced Hyperinsulinism (β-Cell MCT1 Overexpression)
		8.9 Allan-Herndon-Dudley Syndrome (MCT8 Deficiency)
			8.9.1 Clinical Presentation
			8.9.2 Metabolic Derangement
			8.9.3 Genetics
			8.9.4 Diagnostic Tests
			8.9.5 Treatment and Prognosis
		8.10 Familial Cataract, Microcornea Syndrome (MCT12 Deficiency)
		References
	9: Disorders of Creatine Metabolism
		9.1	 Clinical Presentation
			9.1.1	 Arginine: Glycine Amidinotransferase (AGAT) Deficiency
			9.1.2	 Guanidinoacetate Methyltransferase (GAMT) Deficiency
			9.1.3	 Creatine Transporter (CRTR) Deficiency
			9.1.4	 Autosomal Dominant Renal Fanconi syndrome and Kidney Failure Due to Partial AGAT Deficiency
		9.2	 Metabolic Derangement
		9.3	 Genetics
		9.4	 Diagnostic Tests
			9.4.1	 In Vivo Brain MRS and MRI
			9.4.2	 Metabolite Analysis
			9.4.3	 Molecular Genetic Investigations
			9.4.4	 Biochemical Functional Investigations
			9.4.5	 Prenatal Diagnosis
			9.4.6	 Newborn Screening
		9.5	 Treatment and Prognosis
			9.5.1	 AGAT Deficiency
			9.5.2	 GAMT Deficiency
			9.5.3	 CRTR Deficiency
			9.5.4	 Autosomal Dominant Renal Fanconi syndrome and Kidney Failure Due to Dominant GATM Variants
		References
	10: Disorders of Oxidative Phosphorylation
		10.1 Clinical Presentation
			10.1.1	 Neonatal and Infantile Presentations
			10.1.2	 Presentation in Childhood and Adolescence
			10.1.3	 Adult-Onset Disorders
		10.2 Metabolic Derangement
		10.3 Genetics
			10.3.1	 Mitochondrial DNA Mutations
			10.3.2	 Nuclear Gene Defects
			10.3.3	 Frequency of Mutations
		10.4 Diagnostic Tests
			10.4.1	 Screening Tests
			10.4.2	 Muscle and Other Tissue Biopsies
			10.4.3	 Molecular Genetic Investigations
		10.5 Treatment and Prognosis
			10.5.1	 Treatable Disorders
			10.5.2	 Supportive Management
			10.5.3	 Vitamin and Cofactor Cocktails
			10.5.4	 Experimental Approaches
			10.5.5	 Genetic Counselling and Prenatal and Preimplantation Genetic Diagnosis
			10.5.6	 Prognosis
		References
	11: Disorders of Pyruvate Metabolism and the Tricarboxylic Acid Cycle
		11.1 Pyruvate Carboxylase (PC) Deficiency
			11.1.1	 Clinical Presentation
			11.1.2	 Metabolic Derangement
			11.1.3	 Genetics
			11.1.4	 Diagnostic Tests
			11.1.5	 Treatment and Prognosis
		11.2 Phosphoenolpyruvate Carboxykinase (PEPCK) Deficiency
		11.3 Pyruvate Dehydrogenase Complex (PDHC) Deficiency
			11.3.1	 Clinical Presentation
			11.3.2	 Metabolic Derangement
			11.3.3	 Genetics
			11.3.4	 Diagnostic Tests
			11.3.5	 Treatment and Prognosis
		11.4 Dihydrolipoamide Dehydrogenase (DLD) Deficiency
			11.4.1	 Clinical Presentation
			11.4.2	 Metabolic Derangement
			11.4.3	 Genetics
			11.4.4	 Diagnostic Tests
			11.4.5	 Treatment and Prognosis
		11.5 2-Ketoglutarate Dehydrogenase Complex (KDHC) Deficiency
			11.5.1	 Clinical Presentation
			11.5.2	 Metabolic Derangement
			11.5.3	 Genetics
			11.5.4	 Diagnostic Tests
			11.5.5	 Treatment and Prognosis
		11.6 Succinyl-CoA Ligase (SUCL) Deficiency
		11.7 Succinate Dehydrogenase (SDH) Deficiency
		11.8 Fumarase (FH) Deficiency
		11.9 Mitochondrial Aconitase (ACO) deficiency
		11.10 Mitochondrial Isocitrate Dehydrogenase (IDH) deficiency
		11.11 Malate-Aspartate Shuttle (MAS) defects
		11.12 Mitochondrial Citrate Carrier Deficiency
		11.13 Mitochondrial Pyruvate Carrier (MPC) deficiency
		11.14 NAD(P)HX System Repair Defects
		11.15 Protein-Bound Lipoic Acid Defects and Defects in Cofactors
		References
	12: Disorders of Mitochondrial Fatty Acid Oxidation & Riboflavin Metabolism
		12.1 Disorders of Mitochondrial Fatty Acid Oxidation
			12.1.1	 Clinical Presentations
				12.1.1.1	 Fatty Acid Transport Defects
				12.1.1.2	 Carnitine Cycle Defects
				12.1.1.3	 β-Oxidation Defects
				12.1.1.4	 Electron Transfer Defects
				12.1.1.5	 Other Potential Defects
			12.1.2	 Metabolic Derangement
			12.1.3	 Genetics
			12.1.4	 Diagnostic Tests
				12.1.4.1	 Abnormal Metabolites
				12.1.4.2	 In Vitro Studies
				12.1.4.3	 Fasting Studies
				12.1.4.4	 Prenatal Diagnosis
				12.1.4.5	 Newborn Screening
			12.1.5	 Treatment and Prognosis
				12.1.5.1	 Management of Acute Illness
				12.1.5.2	 Long Term Dietary Management
				12.1.5.3	 Drug Treatment
				12.1.5.4	 Monitoring
				12.1.5.5	 Prognosis
		12.2 Defects of Riboflavin Transport & Metabolism
			12.2.1	 Riboflavin Transporter Deficiencies
			12.2.2	 RFVT1 Deficiency
			12.2.3	 FAD Synthase and Mitochondrial FAD Transporter Deficiencies
		References
	13: Disorders of Ketogenesis and Ketolysis
		13.1 Ketogenesis Defects
			13.1.1	 Clinical Presentation
			13.1.2	 Metabolic Derangement
			13.1.3	 Genetics
			13.1.4	 Diagnostic Tests
			13.1.5	 Treatment and Prognosis
		13.2 Defects of Ketone Body Utilisation or Transport
			13.2.1	 Clinical Presentation
			13.2.2	 Metabolic Derangement
			13.2.3	 Genetics
			13.2.4	 Diagnostic Tests
			13.2.5	 Treatment and Prognosis
		13.3 Cytosolic Acetoacetyl-CoA Thiolase Deficiency
		13.4 “Idiopathic“ Ketotic Hypoglycaemia
			13.4.1	 Clinical Presentation
			13.4.2	 Metabolic Derangement
			13.4.3	 Diagnostic Tests
			13.4.4	 Treatment and Prognosis
		13.5 Ketogenic Diets
		13.6 Therapeutic Use of Ketone Bodies and Ketone Esters
		References
III: Small Molecule Disorders
	14: Disorders of Galactose Metabolism
		14.1 Galactose-1-Phosphate Uridylyltransferase (GALT) Deficiency
			14.1.1	 Clinical Presentation
			14.1.2	 Metabolic Derangement
			14.1.3	 Genetics
			14.1.4	 Diagnostic Tests
			14.1.5	 Treatment and Prognosis
		14.2 Uridine Diphosphate Galactose 4′-Epimerase (GALE) Deficiency
			14.2.1	 Clinical Presentation
			14.2.2	 Metabolic Derangement
			14.2.3	 Genetics
			14.2.4	 Diagnostic Tests
			14.2.5	 Treatment and Prognosis
		14.3 Galactokinase (GALK) Deficiency
			14.3.1	 Clinical Presentation
			14.3.2	 Metabolic Derangement
			14.3.3	 Genetics
			14.3.4	 Diagnostic Tests
			14.3.5	 Treatment and Prognosis
		14.4 Galactose Mutarotase (GALM) Deficiency
		14.5 Fanconi-Bickel Syndrome
		14.6 Portosystemic Venous Shunting and Hepatic Arteriovenous Malformations
		References
	15: Disorders of Fructose Metabolism
		15.1	 Essential Fructosuria
			15.1.1	 Clinical Presentation
			15.1.2	 Metabolic Derangement
			15.1.3	 Genetics
			15.1.4	 Diagnosis
			15.1.5	 Differential Diagnosis
			15.1.6	 Treatment and Prognosis
		15.2	 Hereditary Fructose Intolerance
			15.2.1	 Clinical Presentation
			15.2.2	 Metabolic Derangement
			15.2.3	 Genetics
			15.2.4	 Diagnosis
			15.2.5	 Differential Diagnosis
			15.2.6	 Treatment and Prognosis
		15.3	 Fructose-1,6-Bisphosphatase Deficiency
			15.3.1	 Clinical Presentation
			15.3.2	 Metabolic Derangement
			15.3.3	 Genetics
			15.3.4	 Diagnosis
			15.3.5	 Differential Diagnosis
			15.3.6	 Treatment and Prognosis
		15.4	 Sorbitol Dehydrogenase Deficiency
			15.4.1	 Clinical Presentation
			15.4.2	 Metabolic Derangement
			15.4.3	 Genetics
			15.4.4	 Diagnosis
			15.4.5	 Treatment and Prognosis
		References
	16: Hyperphenylalaninaemia
		16.1	 Phenylalanine Hydroxylase Deficiency
			16.1.1	 Clinical Presentation
			16.1.2	 Metabolic Derangement
			16.1.3	 Genetics
			16.1.4	 Diagnostic Tests
			16.1.5	 Treatment and Prognosis
				16.1.5.1	 Principles of Treatment
				16.1.5.2	 Monitoring of Treatment
				16.1.5.3	 Alternative Therapies/Experimental Trials
				16.1.5.4	 Compliance with Treatment
				16.1.5.5	 Outcome
				16.1.5.6	 Complications in Adulthood
				16.1.5.7	 Management of Late-Diagnosed PKU
		16.2	 DNAJC12 Deficiency
			16.2.1	 Clinical Presentation
			16.2.2	 Metabolic Derangement
			16.2.3	 Genetics
			16.2.4	 Diagnostic and Confirmatory Tests
			16.2.5	 Treatment and Prognosis
		16.3	 Maternal PKU
			16.3.1	 Clinical Presentation
			16.3.2	 Metabolic Derangement
			16.3.3	 Treatment and Prognosis
				16.3.3.1	 Prevention of the Maternal PKU Syndrome
				16.3.3.2	 Current Practice
				16.3.3.3	 Outcome
		16.4	 HPA and Disorders of Biopterin Metabolism
			16.4.1	 Clinical Presentation
			16.4.2	 Metabolic Derangement
			16.4.3	 Genetics
			16.4.4	 Diagnostic and Confirmatory Tests
				16.4.4.1	 Urine or Blood Pterin Analysis and Blood DHPR Assay
				16.4.4.2	 BH4 Loading Test
				16.4.4.3	 CSF Neurotransmitters
				16.4.4.4	 Confirmatory Tests
				16.4.4.5	 Prenatal Diagnosis
			16.4.5	 Treatment and Prognosis
				16.4.5.1	 Monitoring of Treatment
				16.4.5.2	 Outcome
		References
	17: Disorders of Tyrosine Metabolism
		17.1 Hereditary Tyrosinaemia Type I (Hepatorenal Tyrosinaemia): Fumarylacetoacetate Hydrolase Deficiency
			17.1.1	 Clinical Presentation
			17.1.2	 Metabolic Derangement
			17.1.3	 Genetics
			17.1.4	 Diagnostic Tests
			17.1.5	 Treatment and Prognosis
		17.2 Maleylacetoacetate Isomerase Deficiency (Mild Hypersuccinylacetonaemia, MHSA)
			17.2.1	 Clinical Presentation
			17.2.2	 Metabolic Derangement and Genetics
			17.2.3	 Diagnostic Tests
			17.2.4	 Treatment and Prognosis
		17.3 Hereditary Tyrosinaemia Type II (Oculocutaneous Tyrosinaemia, Richner-Hanhart Syndrome): Hepatic Cytosolic Tyrosine Aminotransferase Deficiency
			17.3.1	 Clinical Presentation
			17.3.2	 Metabolic Derangement
			17.3.3	 Genetics
			17.3.4	 Diagnostic Tests
			17.3.5	 Treatment and Prognosis
		17.4 Hereditary Tyrosinaemia Type III: 4-hydroxyphenylpyruvate Dioxygenase Deficiency
			17.4.1	 Clinical Presentation
			17.4.2	 Metabolic Derangement
			17.4.3	 Genetics
			17.4.4	 Diagnostic Tests
			17.4.5	 Treatment and Prognosis
		17.5 Transient Tyrosinaemia
		17.6 Alkaptonuria: Homogentisate Dioxygenase Deficiency
			17.6.1	 Clinical Presentation
			17.6.2	 Metabolic Derangement
			17.6.3	 Genetics
			17.6.4	 Diagnostic Tests
			17.6.5	 Treatment and Prognosis
		17.7 Hawkinsinuria
			17.7.1	 Clinical Presentation
			17.7.2	 Metabolic Derangement
			17.7.3	 Genetics
			17.7.4	 Diagnostic Tests
			17.7.5	 Treatment and Prognosis
		References
	18: Branched-Chain Organic Acidurias/Acidaemias
		18.1 Maple Syrup Urine Disease, Isovaleric Aciduria, Propionic Aciduria, Methylmalonic Aciduria
			18.1.1	 Clinical Presentation
				18.1.1.1	 Severe Neonatal-Onset Form
				18.1.1.2	 Acute Intermittent Late-Onset Form
				18.1.1.3	 Chronic, Progressive Forms
				18.1.1.4	 Complications
			18.1.2	 Metabolic Derangement
			18.1.3	 Genetics
			18.1.4	 Diagnostic Tests
			18.1.5	 Treatment and Prognosis
				18.1.5.1	 Principles of Treatment
				18.1.5.2	 Specific Adjustments
		18.2 3-Methylcrotonyl Glycinuria
			18.2.1	 Clinical Presentation
			18.2.2	 Metabolic Derangement
			18.2.3	 Genetics
			18.2.4	 Diagnostic Tests
			18.2.5	 Treatment and Prognosis
		18.3 3-Methylglutaconic Aciduria
		18.4 Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency
		18.5 2-Methyl-3-Hydroxybutyryl-CoA Dehydrogenase Deficiency
		18.6 Isobutyryl-CoA Dehydrogenase Deficiency
		18.7 3-Hydroxyisobutyric Aciduria
		18.8 Malonyl-CoA Decarboxylase Deficiency
		18.9 ACSF3 Deficiency
		18.10 Short-Chain Enoyl-CoA Hydratase 1 (ECHS1) Deficiency
		References
	19: Disorders of the Urea Cycle and Related Enzymes
		19.1 Mitochondrial Urea Cycle Disorders
		19.2 Cytosolic Urea Cycle Disorders
		19.3 Urea Cycle Mitochondrial Transporter Defects
			19.3.1	 Hyperornithinemia, Hyperammonaemia and Homocitrullinuria (HHH) Syndrome
			19.3.2 Citrin Deficiency
		19.4 Urea Cycle Defects Due to Deficiencies of Ancillary Enzymes
			19.4.1	 Δ1-Pyrroline-5-Carboxylate Synthetase (P5CS) Deficiency
			19.4.2	 Carbonic Anhydrase Va (CAVA) Deficiency
		19.5 Transient Hyperammonaemia of the Newborn (THAN)
		References
	20: Disorders of Sulfur Amino Acid Metabolism
		20.1 Methionine S-Adenosyltransferase Deficiency (Mudd’s Disease)
			20.1.1	 Clinical Presentation
			20.1.2	 Metabolic Derangement
			20.1.3	 Genetics
			20.1.4	 Diagnostic Tests
			20.1.5	 Treatment and Prognosis
		20.2 Methanethiol Oxidase Deficiency
			20.2.1	 Clinical Presentation
			20.2.2	 Metabolic Derangement
			20.2.3	 Genetics
			20.2.4	 Diagnostic Tests
			20.2.5	 Treatment and Prognosis
		20.3 Glycine N-Methyltransferase Deficiency
			20.3.1	 Clinical Presentation
			20.3.2	 Metabolic Derangement
			20.3.3	 Genetics
			20.3.4	 Diagnostic Tests
			20.3.5	 Treatment and Prognosis
		20.4 S-Adenosylhomocysteine Hydrolase Deficiency
			20.4.1	 Clinical Presentation
			20.4.2	 Metabolic Derangement
			20.4.3	 Genetics
			20.4.4	 Diagnostic Tests
			20.4.5	 Treatment and Prognosis
		20.5 Adenosine Kinase Deficiency
		20.6 Cystathionine β-Synthase Deficiency
			20.6.1	 Clinical Presentation
			20.6.2	 Metabolic Derangement
			20.6.3	 Genetics
			20.6.4	 Diagnostic Tests
			20.6.5	 Treatment and Prognosis
		20.7 Cystathionine γ-Lyase Deficiency
			20.7.1	 Clinical Presentation
			20.7.2	 Metabolic Derangement
			20.7.3	 Genetics
			20.7.4	 Diagnostic Tests
			20.7.5	 Treatment and Prognosis
		20.8 Sulfide:Quinone Oxidoreductase Deficiency
			20.8.1	 Clinical Presentation
			20.8.2	 Metabolic Derangement
			20.8.3	 Genetics
			20.8.4	 Diagnostic Tests
			20.8.5	 Treatment and Prognosis
		20.9 Ethylmalonic Encephalopathy
			20.9.1	 Clinical Presentation
			20.9.2	 Metabolic Derangement
			20.9.3	 Genetics
			20.9.4	 Diagnostic Tests
			20.9.5	 Treatment and Prognosis
		20.10 Molybdenum Cofactor Deficiency
			20.10.1	 Clinical Presentation
			20.10.2	 Metabolic Derangement
			20.10.3	 Genetics
			20.10.4	 Diagnostic Tests
			20.10.5	 Treatment and Prognosis
		20.11 Isolated Sulfite Oxidase Deficiency
			20.11.1	 Clinical Presentation
			20.11.2	 Metabolic Derangement
			20.11.3	 Genetics
			20.11.4	 Diagnostic Tests
			20.11.5	 Treatment and Prognosis
		References
	21: Disorders of Ornithine and Proline Metabolism
		21.1 Hyperornithinaemia Due to Ornithine Aminotransferase Deficiency (Gyrate Atrophy of the Choroid and Retina)
			21.1.1	 Clinical Presentation
			21.1.2	 Metabolic Derangement
			21.1.3	 Genetics
			21.1.4	 Diagnostic Tests
			21.1.5	 Treatment and Prognosis
		21.2 Hyperornithinaemia, Hyperammonaemia and Homocitrullinuria (HHH) Syndrome
			21.2.1	 Clinical Presentation
			21.2.2	 Metabolic Derangement
			21.2.3	 Genetics
			21.2.4	 Diagnostic Tests
			21.2.5	 Treatment and Prognosis
		21.3 Δ1-Pyrroline-5-Carboxylate Synthetase Deficiency
			21.3.1	 Clinical Presentation
			21.3.2	 Metabolic Derangement
			21.3.3	 Genetics
			21.3.4	 Diagnostic Tests
			21.3.5	 Treatment and Prognosis
		21.4 Δ1-Pyrroline-5-Carboxylate Reductase Deficiency 1 (PYCR1) and 2 (PYCR2)
		21.5 Proline Dehydrogenase (Proline Oxidase) Deficiency (Hyperprolinaemia Type I)
			21.5.1	 Clinical Presentation
			21.5.2	 Metabolic Derangement
			21.5.3	 Genetics
			21.5.4	 Diagnostic Tests
			21.5.5	 Treatment and Prognosis
		21.6 Δ1-Pyrroline-5-Carboxylate Dehydrogenase Deficiency (Hyperprolinaemia Type II)
			21.6.1	 Clinical Presentation
			21.6.2	 Metabolic Derangement
			21.6.3	 Genetics
			21.6.4	 Diagnostic Tests
			21.6.5	 Treatment and Prognosis
		21.7 Polyamine Synthetic Defects
		21.8 Ornithine Decarboxylase (ODC) Superactivity Syndrome
		21.9 Spermine Synthase Deficiency (Snyder Robinson Syndrome)
		References
	22: Cerebral Organic Acid Disorders and Other Disorders of Lysine Catabolism
		22.1 Hyperlysinaemia (2-Aminoadipic Semialdehyde Synthase Deficiency)/Saccharopinuria
			22.1.1	 Clinical Presentation
			22.1.2	 Metabolic Derangement
			22.1.3	 Genetics
			22.1.4	 Diagnostic Tests
			22.1.5	 Treatment and Prognosis
		22.2 Hydroxylysinuria (Hydroxylysine Kinase Deficiency)
		22.3 2-Aminoadipic and 2-Oxoadipic Aciduria (DHTKD1 Deficiency)
			22.3.1	 Clinical Presentation
			22.3.2	 Metabolic Derangement
			22.3.3	 Genetics
			22.3.4	 Diagnostic Tests
			22.3.5	 Treatment and Prognosis
		22.4 Glutaric Aciduria Type I (Glutaryl-CoA Dehydrogenase Deficiency)
			22.4.1	 Clinical Presentation
			22.4.2	 Metabolic Derangement
			22.4.3	 Genetics
			22.4.4	 Diagnostic Tests
			22.4.5	 Treatment and Prognosis
		22.5 Glutaric Aciduria Type II (Multiple Acyl-CoA Dehydrogenase Deficiency)
		22.6 Glutaric Aciduria Type III (Succinate Hydroxymethylglutarate CoA-Transferase Deficiency)
			22.6.1	 Clinical Presentation
			22.6.2	 Metabolic Derangement
			22.6.3	 Genetics
			22.6.4	 Diagnostic Tests
			22.6.5	 Treatment and Prognosis
		22.7 L-2-Hydroxyglutaric Aciduria (L-2-Hydroxyglutaric Dehydrogenase Deficiency)
			22.7.1	 Clinical Presentation
			22.7.2	 Metabolic Derangement
			22.7.3	 Genetics
			22.7.4	 Diagnostic Tests
			22.7.5	 Treatment and Prognosis
		22.8 D-2-Hydroxyglutaric Aciduria Type I (D-2-Hydroxyglutarate Dehydrogenase Deficiency) and Type II (Isocitrate Dehydrogenase 2 Deficiency)
			22.8.1	 Clinical Presentation
			22.8.2	 Metabolic Derangement
			22.8.3	 Genetics
			22.8.4	 Diagnostic Tests
			22.8.5	 Treatment and Prognosis
		22.9 D-2- and L-2-Hydroxyglutaric Aciduria (Mitochondrial Citrate Carrier or SLC25A1 Deficiency)
			22.9.1	 Clinical Presentation
			22.9.2	 Metabolic Derangement
			22.9.3	 Genetics
			22.9.4	 Diagnostic Tests
			22.9.5	 Treatment and Prognosis
		22.10 N-Acetylaspartic Aciduria (Aspartoacylase or Aminoacylase 2 Deficiency) (Canavan Disease)
			22.10.1	 Clinical Presentation
			22.10.2	 Metabolic Derangement
			22.10.3	 Genetics
			22.10.4	 Diagnostic Tests
			22.10.5	 Treatment and Prognosis
		22.11 Aminoacylase 1 Deficiency
			22.11.1	 Diagnostic Tests
			22.11.2	 Treatment and Prognosis
		22.12 Hypoacetylaspartia (L-Aspartate N-Acetyltransferase Deficiency)
		22.13 Malate-Aspartate Shuttle Defects
		References
	23: Nonketotic Hyperglycinaemia and Lipoate Deficiency Disorders
		23.1 Definition
		23.2 Clinical Presentation
			23.2.1	 Severe Classic NKH
			23.2.2	 Attenuated Classic NKH
			23.2.3	 Lipoate Disorders Including Variant NKH
		23.3 Metabolic Abnormalities
		23.4 Genetics
		23.5 Diagnostic Tests
		23.6 Treatment
		23.7 Prognosis
		References
	24: Disorders of Glutamine, Serine and Asparagine Metabolism
		24.1 Inborn Errors of Glutamine Metabolism
			24.1.1	 Glutamine Synthetase Deficiency
			24.1.2	 NAD Synthesis Defect
			24.1.3	 Glutaminase Deficiency
			24.1.4	 Glutaminase Hyperactivity
		24.2 Inborn Errors of Serine Metabolism
			24.2.1	 3-Phosphoglycerate Dehydrogenase Deficiency
			24.2.2	 Phosphoserine Aminotransferase Deficiency
			24.2.3	 3-Phosphoserine Phosphatase Deficiency
			24.2.4	 Brain Serine Transporter Deficiency
			24.2.5	 Serine Palmitoyltransferase Defects
		24.3 Inborn Errors of Asparagine Metabolism
			24.3.1	 Asparagine Synthetase Deficiency
		References
	25: Disorders of Amino Acid Transport at the Cell Membrane
		25.1 Cystinuria
			25.1.1	 Clinical Presentation
			25.1.2	 Metabolic Derangement
			25.1.3	 Genetics
			25.1.4	 Diagnostic Tests
			25.1.5	 Treatment and Prognosis
		25.2 Asymptomatic Amino Acidurias: Iminoglycinuria and Dicarboxylic Amino Aciduria
		25.3 Lysinuric Protein Intolerance
			25.3.1	 Clinical Presentation
			25.3.2	 Metabolic Derangement
			25.3.3	 Genetics
			25.3.4	 Diagnostic Tests
			25.3.5	 Treatment and Prognosis
		25.4 Hartnup Disease
			25.4.1	 Clinical Presentation
			25.4.2	 Metabolic Derangement
			25.4.3	 Genetics
			25.4.4 Diagnostic Tests
			25.4.5	 Treatment and Prognosis
		25.5 Collectrin Deficiency
		25.6 SLC7A5/Brain Neutral Amino Acid Transporter Deficiency
		25.7 SLC7A8/LAT2 Neutral Amino Acid Transporter Deficiency
		25.8 SLC6A6/Taurine Transporter Deficiency
		References
	26: Cystinosis
		26.1	 Infantile Cystinosis
			26.1.1	 Clinical Presentation
			26.1.2	 Metabolic Derangement
			26.1.3	 Genetics
			26.1.4	 Diagnostic Tests
			26.1.5	 Treatment
		26.2	 Late-Onset Cystinosis
		26.3	 Ocular Cystinosis
		References
	27: Biotin-Responsive Disorders
		27.1 Clinical Presentation
			27.1.1	 Holocarboxylase Synthetase Deficiency
			27.1.2	 Biotinidase Deficiency
			27.1.3	 Sodium-Dependent Multivitamin Transporter Deficiency (SLC5A6)
			27.1.4	 Acquired Biotin Deficiency
		27.2 Metabolic Derangement
		27.3 Genetics
			27.3.1	 Holocarboxylase Synthetase Deficiency
			27.3.2	 Biotinidase Deficiency
			27.3.3	 SLC5A6 Deficiency
		27.4 Diagnostic Tests
			27.4.1	 Holocarboxylase Synthetase Deficiency
			27.4.2	 Biotinidase Deficiency
			27.4.3	 SLC5A6 Deficiency
			27.4.4	 Prenatal Diagnosis
		27.5 Treatment and Prognosis
			27.5.1	 Holocarboxylase Synthetase Deficiency
			27.5.2	 Biotinidase Deficiency
			27.5.3	 SLC5A6 Deficiency
		References
	28: Disorders of Cobalamin and Folate Transport and Metabolism
		28.1	 Disorders of Absorption and Transport of Cobalamin
			28.1.1	 Hereditary Intrinsic Factor Deficiency
			28.1.2	 Defective Transport of Cobalamin by Enterocytes (Imerslund-Gräsbeck Syndrome)
			28.1.3	 Haptocorrin (R Binder) Deficiency
			28.1.4	 Transcobalamin Deficiency
			28.1.5	 Transcobalamin Receptor Deficiency
		28.2	 Disorders of Intracellular Utilisation of Cobalamin
			28.2.1	 Combined Deficiencies of Adenosylcobalamin and Methylcobalamin
				28.2.1.1	 CblF (LMBRD1)
				28.2.1.2	 CblJ (ABCD4)
				28.2.1.3	 CblC (MMACHC)
				28.2.1.4	 Disorders of MMACHC Transcription: CblX (HCFC1) and Related Disorders (HAP11; ZNF143)
				28.2.1.5	 CblD (MMADHC)
			28.2.2	 Adenosylcobalamin Deficiency: CblA (MMAA) & CblB (MMAB)
			28.2.3	 Methylcobalamin Deficiency: CblE (MTRR) & CblG (MTR)
		28.3 Disorders of Absorption and Metabolism of Folate
			28.3.1	 Hereditary Folate Malabsorption (Proton-Coupled Folate Transporter Deficiency, SLC46A1)
			28.3.2	 Cerebral Folate Deficiency (Folate Receptor α Deficiency, FOLR1)
			28.3.3	 Reduced Folate Carrier Deficiency (SLC19A1)
			28.3.4	 Methylenetetrahydrofolate Dehydrogenase Deficiency (MTHFD1)
			28.3.5	 Dihydrofolate Reductase Deficiency (DHFR)
			28.3.6	 Glutamate Formiminotransferase Deficiency (FTCD)
			28.3.7	 Methylenetetrahydrofolate Reductase Deficiency (MTHFR)
			28.3.8	 Methenyltetrahydrofolate Synthetase Deficiency (MTHFS)
			28.3.9	 10-Formyltetrahydrofolate Dehydrogenase Deficiency (ALDH1L2)
			28.3.10	 Serine Hydroxymethyltransferase 2 Deficiency (SHMT2)
		References
	29: Disorders of Thiamine and Pyridoxine Metabolism
		29.1	 Disorders of Thiamine (vitamin B1) Metabolism
			29.1.1	 Thiamine Metabolism Dysfunction Syndrome 1 (SLC19A2, THTR1 Deficiency)
			29.1.2	 Thiamine Metabolism Dysfunction Syndrome 2 (SLC19A3, THTR2 Deficiency)
			29.1.3	 Thiamine Metabolism Dysfunction Syndrome 3 (Microcephaly, Amish Type) and Thiamine Metabolism Dysfunction Syndrome 4 (Bilateral Striatal Degeneration and Progressive Polyneuropathy Type): Mitochondrial TPP Transporter deficiency (SLC
			29.1.4	 Thiamine Metabolism Dysfunction Syndrome 5 (Episodic Encephalopathy Type, TPK1 Deficiency)
			29.1.5	 Thiamine-Responsive α-ketoacid Dehydrogenase Deficiencies
			29.1.6	 Thiamine-Responsive Pyruvate Dehydrogenase Deficiency
			29.1.7	 Thiamine-Responsive Maple Syrup Urine Disease
		29.2	 Disorders of Pyridoxine Metabolism
			29.2.1	 Antiquitin Deficiency (ALDH7A1)
			29.2.2	 Hyperprolinemia Type II
			29.2.3	 Pyridox(am)ine 5’-phosphate Oxidase (PNPO) Deficiency
			29.2.4	 Congenital Hypophosphatasia (Tissue Non Specific Alkaline Phosphatase)
			29.2.5	 Hyperphosphatasia-Mental Retardation Syndrome (HPMRS)
			29.2.6	 PLP Binding protein (PLPBP, Formerly PROSC) Deficiency
			29.2.7	 Other B6 Responsive Disorders
		References
	30: Disorders of Neurotransmission
		30.1	 Gamma Amino Butyric Acid (GABA) Neurotransmitter Disorders
			30.1.1	 Gamma Amino Butyric Acid Transaminase Deficiency
			30.1.2	 Succinic Semialdehyde Dehydrogenase Deficiency
			30.1.3	 Glutamic Acid Decarboxylase (GAD) Deficiency
			30.1.4	 GABA Receptor Mutations
			30.1.5	 GABA Transporter Deficiency
		30.2	 Glutamate Neurotransmitter Disorders
			30.2.1	 Glutamate Receptor Mutations
			30.2.2	 Mitochondrial Glutamate Transporter Defect
		30.3	 Glycine Neurotransmitter Disorders
		30.4	 Choline Neurotransmitter Disorders
		30.5	 Monoamine Neurotransmitter Disorders
			30.5.1	 Tyrosine Hydroxylase Deficiency
			30.5.2	 Aromatic L-Amino Acid Decarboxylase Deficiency
			30.5.3	 Dopamine β-Hydroxylase Deficiency
			30.5.4	 Monoamine Oxidase-A Deficiency
			30.5.5	 Guanosine Triphosphate Cyclohydrolase I-Deficiency
			30.5.6	 Sepiapterin Reductase Deficiency
			30.5.7	 Dopamine Transporter Defect
			30.5.8	 Brain Dopamine-Serotonin Vesicular Transport Defect
			30.5.9	 Other Defects
		30.6	 Synaptic Vesicle Disorders (see also 7 Chap. 44)
			30.6.1	 Disorders of SV Exocytosis
			30.6.2	 Disorders of SV Endocytosis
		References
	31: Disorders of Peptide and Amine Metabolism
		31.1	 Disorders of Trimethylamine Metabolism
			31.1.1	 Trimethylaminuria (Fish Malodour Syndrome)
		31.2	 Disorders of Choline Metabolism
			31.2.1	 Dimethylglycine Dehydrogenase Deficiency
			31.2.2	 Sarcosine Dehydrogenase Deficiency
		31.3	 Disorders of Glutathione Metabolism
			31.3.1	 γ-Glutamylcysteine Synthetase Deficiency (Synonym: Glutamate-Cysteine Ligase Deficiency)
			31.3.2	 Glutathione Synthetase Deficiency
			31.3.3	 γ-Glutamyl Transpeptidase Deficiency (Synonym: Glutathionuria)
			31.3.4	 Dipeptidase Deficiency (Synonym: Cysteinylglycinuria)
			31.3.5	 5-Oxoprolinase Deficiency
			31.3.6	 Glutathione Reductase Deficiency
			31.3.7	 Glutathione Peroxidase 4 Deficiency (Synonym: Spondylometaphyseal Dysplasia, Sedaghatian Type)
			31.3.8	 NRF2 Superactivity (Synonym: Immunodeficiency, Developmental Delay, and Hyperhomocysteinaemia)
		31.4	 Other Disorders of Peptide Metabolism
			31.4.1	 Prolidase Deficiency
			31.4.2	 X-Prolyl Aminopeptidase 3 Deficiency (Synonym: Nephronophthisis-like Nephropathy Type 1)
			31.4.3	 Serum Carnosinase Deficiency (Synonym: Carnosinemia)
			31.4.4	 Homocarnosinosis
		References
	32: Disorders of Purine and Pyrimidine Metabolism
		32.1	 Diseases with Birth Defects, Prenatal or Early Onset of Severe Symptoms with Malformations or Neurological Impairment
			32.1.1	 Bifunctional Enzyme Phosphoribosyl-Aminoimidazole Carboxylase/Phosphoribosyl-Aminoimidazole-Succinocarboxamide Synthetase Deficiency
			32.1.2	 Adenylosuccinate Lyase Deficiency
			32.1.3	 AICAR Transformylase/IMP Cyclohydrolase Deficiency
			32.1.4	 Phosphoribosylpyrophosphate Synthetase 1 Deficiency
			32.1.5	 AMP Deaminase-2 Deficiency
			32.1.6	 Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency
			32.1.7	 Adenylate Cyclase 5-Related Dyskinesia
			32.1.8	 IMP Dehydrogenase Mutations
			32.1.9	 Inosine Triphosphate Pyrophosphatase (ITPase) Deficiency
			32.1.10	 Carbamoylphosphate Synthetase II, Aspartate Transcarbamylase, Dihydroorotase Deficiency
			32.1.11	 Dihydroorotate Dehydrogenase Deficiency
			32.1.12	 Dihydropyrimidine Dehydrogenase Deficiency
			32.1.13	 Dihydropyrimidinase Deficiency
			32.1.14	 β-Ureidopropionase Deficiency
			32.1.15	 Cytosolic 5′-Nucleotidase Superactivity
		32.2	 Diseases with Predominant Kidney Stones or Kidney Involvement
			32.2.1	 PRPS1 Overactivity
			32.2.2	 Hereditary Xanthinuria
			32.2.3	 Adenine Phosphoribosyltransferase Deficiency
			32.2.4	 Uric Acid Transport Defects: Hypo- and Hyperuricemia
		32.3	 Diseases with Predominant Immunologic or Hematological Symptoms
			32.3.1	 Adenosine Deaminase 1 Deficiency
			32.3.2	 Adenosine Deaminase 2 Deficiency
			32.3.3	 Purine Nucleoside Phosphorylase Deficiency
			32.3.4	 Adenylate Kinase Deficiencies
			32.3.5	 Adenosine Deaminase 1 Overactivity
			32.3.6	 Uridine Monophosphate Synthase Deficiency
			32.3.7	 Cytosolic 5′-Nucleotidase 3A Deficiency
			32.3.8	 Hyper-IgM Syndromes
			32.3.9 Ecto-5′-Nucleotidase (NT5E) Deficiency
		32.4	 Diseases with Predominant Muscular Involvement
			32.4.1	 AMP Deaminase 1 Deficiency
			32.4.2	 Muscle-Specific Adenylosuccinate Synthase Deficiency
		32.5	 Diseases with Predominant Liver Involvement
			32.5.1	 Adenosine Kinase Deficiency
			32.5.2	 Deoxyguanosine Kinase Deficiency
		32.6	 Mitochondrial DNA Depletion Syndromes
			32.6.1	 Deoxyguanosine Kinase Deficiency
			32.6.2	 Ribonucleotide Reductase Deficiency
			32.6.3	 Thymidine Kinase 2 Deficiency
			32.6.4	 Thymidine Phosphorylase Deficiency
		32.7	 Pharmacogenetics
			32.7.1	 Thiopurine S-Methyltransferase and Nudix Hydroxylase 15 Deficiencies
			32.7.2	 Dihydropyrimidine Dehydrogenase Dihydropyrimidinase and Cytidine Deaminase Deficiencies
		References
	33: Disorders of Haem Biosynthesis
		33.1	 X-Linked Sideroblastic Anaemia
		33.2	 The Porphyrias
			33.2.1	 5-Aminolevulinic Acid Dehydratase Porphyria
			33.2.2	 Acute Intermittent Porphyria (AIP)
			33.2.3	 Congenital Erythropoietic Porphyria (CEP) (Gunther Disease)
			33.2.4	 Porphyria Cutanea Tarda (PCT)
			33.2.5	 Hepatoerythropoietic Porphyria
			33.2.6	 Hereditary Coproporphyria and Variegate Porphyria
			33.2.7	 Erythropoietic Protoporphyria and X-Linked Protoporphyria
		References
	34: Disorders in the Transport of Copper, Iron, Magnesium, Manganese, Selenium and Zinc
		34.1	 Copper
			34.1.1	 Wilson Disease
			34.1.2	 Menkes Disease
			34.1.3	 Other Copper Storage Disorders
			34.1.4	 Other Disturbances of Copper Metabolism with a Low Serum Copper
		34.2	 Iron
			34.2.1	 Systemic Iron Overload Syndromes (Haemochromatosis)
				34.2.1.1	 Classic Hereditary Haemochromatosis (Type 1)
				34.2.1.2	 Juvenile Hereditary Haemochromatosis (Type 2)
				34.2.1.3	 TFR2-Related Hereditary Haemochromatosis (Type 3)
				34.2.1.4	 Ferroportin Related Hereditary Haemochromatosis (Type 4A and 4B)
				34.2.1.5	 Neonatal Haemochromatosis
			34.2.2	 Iron Deficiency and Distribution Disorders
				34.2.2.1	 Iron-Refractory Iron Deficiency Anaemia (IRIDA)
				34.2.2.2	 Mild IRIDA with Severe Combined Immune Deficiency
				34.2.2.3	 Atransferrinaemia
				34.2.2.4	 Hypochromic Microcytic Anaemia with Iron Overload Type 1
				34.2.2.5	 Hypochromic Microcytic Anaemia with Iron Overload Type 2
			34.2.3	 Neurodegeneration with Brain Iron Accumulation (NBIA)
				34.2.3.1	 Aceruloplasminaemia
				34.2.3.2	 Neuroferritinopathy
				34.2.3.3	 Pantothenate Kinase-Associated Neurodegeneration (PKAN)
				34.2.3.4	 COASY Associated Neurodegeneration (CoPAN)
				34.2.3.5	 Phosphopantothenoylcysteine Synthetase Deficiency
				34.2.3.6	 PLA2G6-Associated Neurodegeneration (PLAN)
				34.2.3.7	 Fatty Acid Hydroxylase Associated Neurodegeneration (FAHN)
				34.2.3.8	 Mitochondrial Protein Associated Neurodegeneration (MPAN)
				34.2.3.9	 Woodhouse-Sakati Syndrome
				34.2.3.10	 Beta Propellor Protein-Associated Neurodegeneration (BPAN)
				34.2.3.11	 ATP13A2 Deficiency
		34.3	 Magnesium
			34.3.1	 Primary Hypomagnesaemia with Secondary Hypocalcaemia
			34.3.2	 Isolated Dominant Hypomagnesemia
			34.3.3	 Isolated Autosomal Recessive Hypomagnesaemia
			34.3.4	 Hypomagnesaemia with Other Serum Electrolyte Abnormalities and/or Congenital Malformations or with Nephrocalcinosis
		34.4	 Manganese
			34.4.1	 Hypermanganesaemia with Dystonia Type 1 (HMNDYT1)
			34.4.2	 Hypermanganesaemia with Dystonia Type 2 (HMNDYT2)
			34.4.3	 CDG2N-SLC39A8 Deficiency
		34.5	 Selenium
		34.6	 Zinc
			34.6.1	 Acrodermatitis Enteropathica
			34.6.2	 Spondylocheirodysplastic Ehlers-Danlos Syndrome
			34.6.3	 Birk-Landau-Perez Syndrome
			34.6.4	 Transient Neonatal Zinc Deficiency
			34.6.5	 Hyperzincaemia with Hypercalprotectinaemia
			34.6.6	 Familial Hyperzincaemia Without Symptoms
		References
IV: Complex Molecule Disorders and Cellular Trafficking Disorders
	35: Disorders of Intracellular Triglyceride and Phospholipid Metabolism
		35.1	 Inborn Errors of the Common Pathway and of Triglyceride Synthesis and Degradation
			35.1.1	 Glycerol-3-Phosphate Dehydrogenase 1 (GPD1) Deficiency
			35.1.2	 Glycerol Kinase Deficiency
			35.1.3	 1-Acylglycerol-3-Phosphate O-Acyltransferase 2 (AGPAT2) Deficiency
			Lipodystrophies
			35.1.4	 Phosphatidic Acid Phosphatase (PAP; Lipin) Deficiencies
				35.1.4.1	 Lipin-1 (LPIN1) Deficiency
				35.1.4.2	 Lipin-2 (LPIN2) Deficiency
			35.1.5	 Diacylglycerol Kinase Epsilon (DGKE) Deficiency
		35.2	 Inborn Errors of Cytoplasmic Triglyceride Synthesis, Storage and Degradation
			35.2.1	 Diacylglycerol O-Acyltransferase (DGAT) Deficiencies
				35.2.1.1	 Diacylglycerol O-Acyltransferase 1 (DGAT1) Deficiency
				35.2.1.2	 Diacylglycerol O-Acyltransferase 2 (DGAT2) Deficiency
			35.2.2	 Diseases Related to Structural Proteins of Lipid Droplet (LD) Production, Fusion and Maintenance
				35.2.2.1	 Seipin (BSCL2) Deficiency
				35.2.2.2	 CIDEC Deficiency
				35.2.2.3	 Perilipin 1 (PLIN1) Deficiency
			35.2.3	 Neutral Lipid Storage Diseases (NLSDs): ATGL and CGI-58 Deficiencies
				35.2.3.1	 Adipocyte Triglyceride Lipase (ATGL, PNPLA2) Deficiency
				35.2.3.2	 α,β-Hydrolase Domain-Containing 5 (CGI-58, ABHD5) Deficiency
			35.2.4	 Hormone-Sensitive Lipase (HSL, LIPE) Deficiency
		35.3	 Inborn Errors of Phospholipid Biosynthesis and Mitochondrial Phospholipid Metabolism
			35.3.1	 Choline Kinase β (CHKβ) Deficiency
			35.3.2	 Choline-Phosphate Cytidylyltransferase α (CCTα, PCYT1A) Deficiency
			35.3.3	 Phosphatidylserine Synthase 1 (PSS1, PTDSS1) Gain of Function
			35.3.4	 Ethanolamine Phosphotransferase (EPT1, SELENOI) Deficiency
			35.3.5	 Phosphatidylserine Decarboxylase (PISD) Deficiency
			35.3.6	 Acylglycerol Kinase (AGK) Deficiency: Sengers Syndrome
			35.3.7	 SERAC1 Mutations: MEGDEL Syndrome
			35.3.8	 Cardiolipin Remodelling Enzyme (TAZ) Deficiency: Barth Syndrome
		35.4	 Inborn Errors of Phospholipid Remodelling
			35.4.1	 α/β Hydrolase Domain-Containing Protein 12 (ABHD12) Deficiency
			35.4.2	 Phospholipase A2 (PLA2G6, PNPLA9) Deficiency
			35.4.3	 Mitochondrial Calcium Independent Phospholipase A2γ (iPLA2γ, PNPLA8)
			35.4.4	Deficiency of Neuropathy Target Esterase (NTE, PNPLA6)
			35.4.5	 DDHD1 and DDHD2 Mutations
				35.4.5.1	 DDHD1 Mutations (SPG28)
				35.4.5.2	 DDHD2 Mutations (SPG54)
			35.4.6	 CYP2U1 Mutations (SPG56)
			35.4.7	 Lysophosphatidylinositol Acyltransferase (LPIAT1, MBOAT7) Deficiency
		35.5	 Inborn Errors of Phosphoinositide Phosphorylation
		References
	36: Inborn Errors of Lipoprotein Metabolism Presenting in Childhood
		36.1	 Disorders of Low Density Lipoprotein Metabolism
		36.2	 Disorders of Triglyceride (TG) Metabolism
		36.3	 Disorders of High Density Lipoprotein Metabolism
		36.4	 Disorders of Sterol Storage
		36.5	 Conclusion
		References
	37: Disorders of Isoprenoid/Cholesterol Synthesis
		37.1 Mevalonate Kinase Deficiency
		37.2 Porokeratosis
		37.3 Squalene Synthase Deficiency
		37.4 Desmosterol Reductase Deficiency (Desmosterolosis)
		37.5 Lanosterol C14-Demethylase Deficiency
		37.6 Sterol β14-Reductase Deficiency (Hydrops – Ectopic Calcification – Moth-Eaten (HEM) Skeletal Dysplasia or Greenberg Skeletal Dysplasia)
		37.7 Deficiency of the C4-Demethylase Complex
			37.7.1	 C4-Methyl Sterol Oxidase Deficiency (SMO Deficiency)
			37.7.2	 Sterol 4α-Carboxylate 3-Dehydrogenase Deficiency
				37.7.2.1	 CHILD Syndrome in Females
				37.7.2.2	 CK Syndrome in Males
		37.8 Sterol ∆8-∆7 Isomerase Deficiency
			37.8.1	 X-Linked Dominant Chondrodysplasia Punctata 2 or Conradi-Hünermann Syndrome in Females
			37.8.2	 Hemizygous EBP Deficiency in Males
		37.9 Sterol ∆5-Desaturase Deficiency (Lathosterolosis)
		37.10 Smith-Lemli-Opitz Syndrome (7-Dehydrocholesterol Reductase Deficiency)
		37.11 Ichthyosis Follicularis with Atrichia and Photophobia (IFAP) Syndrome
		References
	38: Disorders of Bile Acid Synthesis
		38.1 3β-Hydroxy-∆5-C27-Steroid Dehydrogenase Deficiency
		38.2 ∆4-3-Oxosteroid 5β-Reductase Deficiency
		38.3 Cerebrotendinous Xanthomatosis (Sterol 27-Hydroxylase Deficiency)
		38.4 Oxysterol 7α-Hydroxylase Deficiency
		38.5 Bile Acid Amidation Defect 1: Bile Acid CoA: Amino Acid N-Acyl Transferase Deficiency
		38.6 Bile Acid Amidation Defect 2: Bile Acid CoA Ligase Deficiency
		38.7 Cholesterol 7α-Hydroxylase Deficiency
		38.8 Disorders of Peroxisome Biogenesis, Peroxisomal Import and Peroxisomal β-Oxidation
			38.8.1	 PMP70 Deficiency: ABCD3 Mutations
			38.8.2	 α-Methylacyl-CoA Racemase Deficiency
			38.8.3	 Acyl-CoA Oxidase 2 Deficiency
		References
	39: Disorders of Nucleic Acid Metabolism, tRNA Metabolism and Ribosomal Biogenesis
		39.1	 Nucleotide and Nucleic Acid metabolism
			39.1.1 Disorders of Ectonucleotide Metabolism – Prototype: Ectopic Calcification
			39.1.2 Disorders of Nucleic Acids: Autoinflammatory Phenotype – Prototype: Aicardi-Goutières Syndrome
		39.2	 tRNA Processing Disorders
			39.2.1 Disorders of Pre-tRNA Splicing – Prototype: Pontocerebellar Hypoplasia
			39.2.2 Disorders of tRNA Modification – Prototype: Non-syndromic Intellectual disability
			39.2.3 Disorders of tRNA Aminoacylation: Neurodegenerative and Systemic Disorders
		39.3	 Ribosomal Biogenesis
			39.3.1 Disorders of Pre-rRNA Transcription: Craniofacial Anomalies
			39.3.2 Disorders of 5S rRNA and tRNA Transcription: Neurodegeneration, Leukodystrophy and Systemic Disorders
			39.3.3 Disorders of Pre-rRNA Processing: Skeletal Dysplasia and Systemic Disorders
			39.3.4 Disorders of Maturation of 40S and 60S Ribosomal Subunits – Prototype: Diamond-Blackfan Syndrome
			39.3.5 Disorders of Active 80S Ribosome Assembly: Shwachman-Diamond Syndrome
		References
	40: Disorders of Sphingolipid Synthesis, Sphingolipidoses, Niemann-Pick Disease Type C and Neuronal Ceroid Lipofuscinoses
		40.1	 Disorders of Sphingolipid Synthesis
			40.1.1	 Serine Palmitoyltransferase (Subunit 1 or 2) Deficiency and HSAN1
			40.1.2	 Ketosphinganine Reductase Deficiency and Hyperkeratosis
			40.1.3	 Defects in Ceramide Synthases 1 and 2 and Myoclonic Epilepsy
			40.1.4	 Dihydroceramide Δ4-Desaturase Deficiency and Leukodystrophy
			40.1.5	 Fatty Acid 2-Hydroxylase Deficiency (SPG35/FAHN)
			40.1.6	 GM3 Synthase Deficiency and Amish Epilepsy Syndrome
			40.1.7	 GM2/GD2 Synthase Deficiency (SPG26)
			40.1.8	 Defects in Skin Ceramide Synthesis: Autosomal Recessive Congenital Ichthyoses (ARCI)
			40.1.9	 Sphingomyelin Synthase 2 Mutations and Osteoporosis
			40.1.10	 Mutations in Ceramide Kinase-Like (CERKL) Gene and Retinal Dystrophy
		40.2	 Disorders of Lysosomal Sphingolipid Degradation: Sphingolipidoses
			40.2.1	 Gaucher Disease
			40.2.2	 Acid Sphingomyelinase-Deficient Niemann-Pick Disease (Type A, Type B and Intermediate Forms)
			40.2.3	 GM1 Gangliosidosis
			40.2.4	 GM2 Gangliosidoses
			40.2.5	 Krabbe Disease
			40.2.6	 Metachromatic Leukodystrophy
			40.2.7	 Fabry Disease
			40.2.8	 Farber Disease/Acid Ceramidase Deficiency
			40.2.9	 Prosaposin Deficiency
		40.3	 Disorders of Non-Lysosomal Sphingolipid Degradation
			40.3.1	 Non-lysosomal β-Glucosidase (GBA2) Deficiency: SPG46 and Ataxia
			40.3.2	 Neutral Sphingomyelinase-3 Deficiency
			40.3.3	 Alkaline Ceramidase 3 (ACER3) Deficiency: Infantile Leukodystrophy
			40.3.4	 Sphingosine-1-phosphate Lyase (SGPL1) Deficiency: A Multisystemic Disorder
		40.4	 Niemann-Pick Disease Type C
		40.5	 Neuronal Ceroid Lipofuscinoses
		References
	41: Glycosaminoglycans and Oligosaccharides Disorders: Glycosaminoglycans Synthesis Defects, Mucopolysaccharidoses, Oligosaccharidoses and Sialic Acid Disorders
		41.1 Glycosaminoglycans Synthesis Defects
		41.2 Mucopolysaccharidoses
			41.2.1	 Clinical Presentation
			41.2.2	 Metabolic Derangement
			41.2.3	 Genetics
			41.2.4	 Diagnostic Tests
			41.2.5	 Treatment and Prognosis
		41.3 Oligosaccharidoses and Mucolipidoses
			41.3.1	 Clinical Presentation
			41.3.2	 Metabolic Derangements
			41.3.3	 Genetics
			41.3.4	 Diagnostic Tests
			41.3.5	 Treatment and Prognosis
		References
	42: Inborn Errors of Non-Mitochondrial Fatty Acid Metabolism Including Peroxisomal Disorders
		42.1	 Disorders of Ether Lipid Biosynthesis
			42.1.1	 Peroxin 7 (PEX7) Deficiency (RCDP Type 1)
			42.1.2	 Glycerone-3-Phosphate Acyltransferase (GNPAT) deficiency (RCDP Type 2)
			42.1.3	 Alkylglycerone-3-Phosphate Synthase (AGPS) Deficiency (RCDP Type 3)
			42.1.4	 FAR1 Deficiency (RCDP Type 4)
			42.1.5	 PEX5L Deficiency (RCDP Type 5)
		42.2	 Disorders of Peroxisomal Fatty Acid β-Oxidation
			42.2.1	 X-Linked Adrenoleukodystrophy (ALD)
			42.2.2	 D-Bifunctional Protein (DBP) Deficiency
			42.2.3	 Acyl-CoA Oxidase 1 (ACOX1) Deficiency
			42.2.4	 2-Methylacyl-CoA Racemase (AMACR) Deficiency
			42.2.5	 Sterol Carrier Protein 2 Deficiency
			42.2.6	 PMP70 (ABCD3) Deficiency
			42.2.7	 Acyl-CoA Oxidase 2 (ACOX2) Deficiency
			42.2.8	 Contiguous ABCD1, DXS1357A-Deletion Syndrome (CADDS)
			42.2.9	 Generalized Peroxisomal Fatty Acid Oxidation Deficiencies: Zellweger Spectrum Disorders
		42.3	 Disorders of Peroxisomal Fatty Acid α-Oxidation: Adult Refsum Disease
		42.4	 Disorders of Fatty Acid Chain Elongation and Fatty Acid/Alcohol/Aldehyde Homeostasis
			42.4.1	 FACL4 Deficiency
			42.4.2	 FATP4/ACSVL4/SLC27A4 Deficiency
			42.4.3	 Fatty Acid 2-Hydroxylase (FA2H) Deficiency
			42.4.4	 CYP4F22 Deficiency
			42.4.5	 Sjögren Larsson Syndrome (SLS)
			42.4.6	 Fatty Acid Chain-Elongation Disorders
			42.4.7	 Acetyl-CoA Carboxylase 1 Deficiency
			42.4.8	 ELOVL4 Deficiency
			42.4.9	 ELOVL5 Deficiency
			42.4.10	 ELOVL1 Deficiency
			42.4.11	 Trans-2,3-Enoyl-CoA Reductase Deficiency
			42.4.12	 3-Hydroxyacyl-CoA Dehydratase Deficiency
			42.4.13	 MFSD2A Brain DHA Transporter Deficiency
		42.5	 Disorders of Eicosanoid Metabolism
			42.5.1	 Cytosolic Phospholipase A2∝ Deficiency
			42.5.2	 15-Hydroxyprostaglandin Dehydrogenase and Prostaglandin Transporter Deficiency Causing Primary Hypertrophic Osteoarthropathy (PHOAR)
			42.5.3	 Leukotriene C4 Synthase (LTC4) Deficiency
		References
	43: Congenital Disorders of Glycosylation, Dolichol and Glycosylphosphatidylinositol Metabolism
		43.1 Congenital Disorders of Protein N-Glycosylation
			43.1.1 Phosphomannomutase 2 Deficiency (PMM2-CDG)
			43.1.2	 Mannose-Phosphate-Isomerase Deficiency (MPI-CDG)
			43.1.3	 Glucosyltransferase 1 Deficiency (ALG6-CDG)
			43.1.4	 Mannosyltransferase 1 Deficiency (ALG1-CDG)
			43.1.5	 UDP-GlcNAc:Dol-P-GlcNAc-P Transferase Deficiency (DPAGT1-CDG)
			43.1.6	 Metabolic Derangement
			43.1.7	 Genetics
			43.1.8	 Diagnostic Tests
			43.1.9	 Treatment and Prognosis
			43.1.10	 Golgi α1-2 Mannosidase 1 Deficiency (MAN1B1-CDG)
		43.2 Congenital Disorders of Protein O-Glycosylation
			43.2.1	 Progeroid Variant of Ehlers-Danlos Syndrome (B4GALT7-CDG)
			43.2.2	 GALNT3 Deficiency (GALNT3-CDG)
			43.2.3	 Hereditary Multiple Exostoses (EXT1/EXT2-CDG)
			43.2.4	 Cerebro-Ocular Dysplasia-Muscular Dystrophy Syndromes, Types A1, B1, C1/A2, B2, C2 (POMT1-CDG/POMT2-CDG)
			43.2.5	 Muscle-Eye-Brain Disease, Types A3, B3, C3, RP76/A8,C8 (POMGNT1-CDG/POMGNT2-CDG)
			43.2.6	 O-Fucose-Specific β-1,3-Glucosyltransferase Deficiency (B3GLCT-CDG)
		43.3 Defects in Lipid Glycosylation and in Glycosylphosphatidylinositol Anchor Biosynthesis
			43.3.1	 GM3 Synthase Deficiency (ST3GAL5-CDG)
			43.3.2	 GM2 Synthase Deficiency (B4GALNT1- CDG)
			43.3.3	 PIGA Deficiency (PIGA-CDG)
		43.4 Defects in Multiple Glycosylation Pathways and in Other Pathways Including Dolicholphosphate Biosynthesis
			43.4.1	 Hereditary Inclusion Body Myopathy (GNE-CDG)
			43.4.2	 Congenital Myasthenic Syndrome-12 (GFPT1-CDG)
			43.4.3	 Steroid 5-α-Reductase Deficiency (SRD5A3-CDG)
			43.4.4	 COG6 Deficiency (COG6-CDG)
			43.4.5	 Autosomal Recessive Cutis Laxa Type 2 (ATP6V0A2-CDG)
			43.4.6	 Phosphoglucomutase 1 Deficiency (PGM1-CDG)
			43.4.7	 Golgi Homeostasis Disorders: TMEM199 and CCDC115 Deficiencies
			43.4.8	 Manganese and Zinc Transporter Defect: SLC39A8 Deficiency
		43.5 Congenital Disorders of Deglycosylation (CDDG)
			43.5.1	 N-glycanase 1 (NGLY1) Deficiency
			43.5.2	 Lysosomal Storage Disorders
		References
	44: Disorders of Cellular Trafficking
		44.1	 Cellular Mechanisms of Trafficking
			44.1.1	 Membrane Trafficking
			44.1.2	 Membrane Contact Sites
			44.1.3	 Other Types of Cellular Trafficking
		44.2	 Cellular Trafficking in the Nervous System: Polarization and Compartmentalization
			44.2.1	 Trafficking Defects in the Neuronal Soma (ER-Golgi-PM-Endosome-Lysosome-Autophagosome)
			44.2.2	 Axonal and Other Cytoskeleton Related Trafficking Defects
			44.2.3	 Synaptic Vesicle Cycle Disorders
			44.2.4	 Dendrites and Post-synaptic Neuron Compartment Traffic Defects
			44.2.5	 Glia Trafficking Disorders
		44.3	 Main Clinical Presentations of Cellular Trafficking Disorders
			44.3.1	 Neurological Manifestations
			44.3.2	 Extra-Neurological Manifestations
		References
V: Appendices
	45: Medications Used in the Treatment of Inborn Errors of Metabolism
Index