Inborn Errors of Metabolism - Early Detection, Key Symptoms and Therapeutic Options

1.Newborn screening11
2.Diagnostic procedures15
2.1.Biochemical investigations15
2.2.Biopsies, enzymology, histopathology17
2.3.Mutation analyses17
2.4.Function tests17
2.5.Neuroradiological investigations17
2.6.Post-mortem investigations18
3.Biochemical key symptoms19
3.1.Hyperammonaemia19
3.2.Hypoglycaemia21
3.3.Metabolic acidosis21
3.4.Hyperlactataemia22
4.Clinical key symptoms25
4.1.The critically ill neonate – metabolic emergencies in the neonate25
4.2.Acute and chronic encephalopathies27
4.3.Psychomotor impairment27
4.4.Cardiomyopathy29
4.5.Dysmorphias30
4.6.Hepatopathy32
4.7.Non-immune fetal hydrops32
4.8.Psychiatric symptoms35
4.9.Ophthalmological problems37
4.10.Haematological problems38
5.Selection of metabolic diseases (symptoms, diagnosis, treatment)39
5.1.Phenylketonuria (PKU)39
5.2.Maple syrup urine disease (MSUD)41
5.3.Tyrosinaemia type I42
5.4.Disorders of methionine and homocysteine metabolism44
5.4.1.Classical homocystinuria45
5.4.2.Methylene tetrahydrofolate reductase (MTHFR) deficiency45
5.4.3.Sulfite oxidase deficiency and molybdenum cofactor deficiency46
5.5.Non-ketotic hyperglycinaemia47
5.6.Urea cycle disorders47
5.7.Organic acidurias51
5.7.1.Propionic aciduria51
5.7.2.Methylmalonic aciduria52
5.7.3.Isovaleric aciduria53
5.7.4.Glutaric aciduria type I54
5.8.Disorders of biotin metabolism55
5.9.Mitochondrial disorders56
5.10.Disorders of the carnitine cycle, fatty acid oxidation and ketone body metabolism60
5.10.1.Carnitine transporter defect (organic cation carnitine transporter 2 defect, OCTN2,
primary carnitine deficiency)61
5.10.2.Carnitine cycle disorders61
5.10.2.1.Carnitine palmitoyltransferase 1 (CPT 1) deficiency61
5.10.2.2.Carnitine/acylcarnitine translocase (CACT) deficiency62
5.10.2.3.Carnitine palmitoyltransferase 2 (CPT 2) deficiency62
5.10.3.Disorders of b-oxidation of fatty acids62
5.10.3.1.Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency62
5.10.3.2.Mitochondrial trifunctional protein (mTFP) deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase
(LCHAD) deficiency, long-chain 3-ketoacyl-CoA thiolase (LKAT) deficiency63
5.10.3.3.Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency64
5.10.3.4.Short-chain acyl-CoA dehydrogenase (SCAD) deficiency68
5.10.4.Multiple acyl-CoA dehydrogenase (MAD) deficiency (or electron transfer defect, ETF/ETF-DH,
or glutaric aciduria type II)68
5.10.5.Defects of ketone body metabolism68
5.10.5.1.3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase deficiency68
5.10.5.2.3-Hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency69
5.11.Disturbances of carbohydrate metabolism69
5.11.1.Classical galactosaemia69
5.11.2.Hereditary fructose intolerance (HFI)71
5.11.3.Glycogen storage diseases (GSD)72
5.11.3.1.Glycogenosis I (GSD I, von Gierke's disease)72
5.11.3.2.Glycogenosis III (GSD III, Cori/Forbes disease)74
5.11.3.3.Glycogenosis V (GSD V, McArdle's disease)75
5.11.3.4.Glycogenosis IX (GSD IX)76
5.12.Congenital hyperinsulinism76
5.13.Lysosomal storage diseases (LSD)77
5.13.1.Gaucher's disease78
5.13.2.Fabry's disease79
5.13.3.Mucopolysaccharidoses80
5.14.Peroxisomal disorders81
5.14.1.Group I: Disorders of peroxisome biogenesis81
5.14.2.Group II: Isolated defects of peroxisomal pathways83
5.15.Congenital disorders of glycosylation (CDG)84
5.15.1.PMM2-CDG (formerly CDG type Ia)86
5.15.2.MPI-CDG (formerly CDG type Ib)86
5.15.3.SLC35C1-CDG (formerly CDG type IIc)86
5.16.Disorders of purine and pyrimidine metabolism86
5.16.1.Increased production of uric acid88
5.16.2.Reduced production of uric acid88
5.16.3.Increased excretion of uric acid88
5.16.4.Therapeutic options in disorders of purine and pyrimidine metabolism88
5.17.Disorders of creatine metabolism88
5.17.1.Guanidinoacetate methyltransferase (GAMT) deficiency89
5.17.2.Arginine:glycine-amidinotransferase (AGAT) deficiency89
5.17.3.Creatine transporter deficiency90
5.18.Hyperlipidaemias90
5.18.1.Hypercholesterolaemia90
5.18.2.Hypertriglyceridaemia92
5.18.2.1.Hyperchylomicronaemia92
5.18.2.2.Familial hypertriglyceridaemia93
5.18.3.Mixed hyperlipidaemias93
5.18.3.1.Familial combined hyperlipidaemia93
5.18.3.2.Familial dysbetalipoproteinaemia (remnant hyperlipidaemia, broad beta disease)93
6.Tables – special metabolic investigations, dietetic treatment, emergency
medication95
7.Literature and internet links101
7.1.General literature101
7.2.Internet links101
8.Abbreviations103
Index105