Laboratory Diagnosis in Neurology, 1 Ed.

17 Metabolic Diseases

F. Ebinger

Currently, over 300 diseases caused by congenital metabolic anomalies are known, and their numbers are increasing (Fernandes et al., 2000; Blau et al., 2003; Zschocke and Hoffmann, 2004). In most cases they are diagnosed in childhood. However, many metabolic disorders may in some cases not become manifest until adolescence or adulthood, and these later manifestations can differ significantly from the often rapidly progressive clinical course of the same metabolic defects when they appear in early childhood. Symptoms such as neuropathy, ataxia, dystonia, epilepsy, psychosis, and dementia suggest an inflammatory, toxic, vascular, or psychiatric disease. Frequently, a “neurodegenerative disease of unknown etiology” is diagnosed. The first symptoms are often mild or intermittent and can be interpreted correctly only in retrospect. The most important step in diagnosing such diseases is to think of a metabolic etiology in the first place. Table 17.1 lists the cardinal symptoms of selected neurometabolic diseases when they manifest in adulthood (Gray et al., 2000; Saudubray and Charpentier, 2001).

Table 17.1 Neurological symptoms of congenital metabolic disorders in adulthood

Symptoms

Metabolic defect

Clinical manifestations

Myopathy, stress intolerance

Mitochondrial disorder

Electron transport chain defects

 

Lysosomal disorder

Glycogen storage disease type II, Danon's disease

 

Defect in purine metabolism

Myoadenylate deaminase deficiency

Neuropathy

Lysosomal disorder

Fabry's disease, Krabbe's disease, metachromatic leukodystrophy

 

Peroxisomal disorder

Refsum's disease, adrenoleukodystrophy/adrenomyeloneuropathy

 

Mitochondrial disorder

Electron transport chain defects

 

Defect in cholesterol metabolism

Cerebrotendinous xanthomatosis

 

Defect in heme biosynthesis

Porphyria

Spinal muscular atrophy

Lysosomal disorder

GM2 gangliosidosis

Spasticity

Mitochondrial disorder

Electron transport chain defects

 

Lysosomal disorder

GM1 gangliosidosis, GM2 gangliosidosis, Gaucher's disease type 3, Krabbe's disease, metachromatic leukodystrophy, Salla disease

 

Peroxisomal disorder

Refsum's disease, adrenoleukodystrophy/adrenomyeloneuropathy

 

Defect in cholesterol metabolism

Cerebrotendinous xanthomatosis

 

Defect in urea cycle

Arginase deficiency

Progressive ataxia

Mitochondrial disorder

Pyruvate dehydrogenase deficiency, electron transport chain defects

 

Lysosomal disorder

GM2 gangliosidosis, metachromatic leukodystrophy, Niemann-Pick disease type C, sialidosis, Salla disease

 

Peroxisomal disorder

Refsum's disease, adrenoleukodystrophy/adrenomyeloneuropathy

 

Defect in cholesterol metabolism

Cerebrotendinous xanthomatosis

 

Defect in copper metabolism

Wilson's disease

 

Defect in lipid metabolism

Abetalipoproteinemia

Extrapyramidal symptoms

Mitochondrial disorder

Electron transport chain defects

 

Lysosomal disorder

GM1 gangliosidosis, GM2 gangliosidosis (Tay-Sachs disease, Sandhoff’s disease), metachromatic leukodystrophy, Niemann–Pick disease type C, neuronal ceroid lipofuscinosis (Spielmeyer–Vogt disease, Kufs’ disease)

 

Peroxisomal disorder

Adrenoleukodystrophy

 

Defect in cholesterol metabolism

Cerebrotendinous xanthomatosis

 

Defect in copper metabolism

Wilson's disease

 

Defect in purine metabolism

Lesch-Nyhan syndrome

 

Organic acid disorder

Glutaric aciduria type I

Leukodystrophy/leukoencephalopathy (specific patterns of distribution)

Mitochondrial disorder

Lysosomal disorder

Peroxisomal disorder

Defect in cholesterol metabolism

Organic acid disorder

Electron transport chain defects

Krabbe's disease, metachromatic leukodystrophy

Adrenoleukodystrophy

Cerebrotendinous xanthomatosis

Canavan's disease

(Myoclonic) epilepsy

Mitochondrial disorder

Lysosomal disorder

Pyruvate dehydrogenase deficiency, electron transport chain defects

Sialidosis, neuronal ceroid lipofuscinosis (Spielmeyer-Vogt disease, Kufs’ disease)

Behavioral abnormalities, psychosis, dementia

Mitochondrial disorder

Lysosomal disorder

Electron transport chain defects

Fabry's disease, GM2 gangliosidosis (Tay–Sachs disease, Sandhoff’s disease), Gaucher's disease type 3, metachromatic leukodystrophy, Niemann-Pick disease type C, neuronal ceroid lipofuscinosis (Spielmeyer-Vogt disease, Kufs’ disease)

 

Peroxisomal disorder

Adrenoleukodystrophy

 

Defect in cholesterol metabolism

Cerebrotendinous xanthomatosis

 

Defect in copper metabolism

Wilson's disease

 

Defect in amino acid metabolism

Homocystinuria

 

Defect in urea cycle

Ornithine transcarbamylase deficiency

Loss of vision

Mitochondrial disorder

Electron transport chain defects

 

Lysosomal disorder

Neuronal ceroid lipofuscinosis (Spielmeyer-Vogt disease), sialidosis

 

Peroxisomal disorder

Refsum's disease

 

Defect in urea cycle

Ornithine aminotransferase deficiency

Ophthalmoplegia

Mitochondrial disorder

Electron transport chain defects

 

Lysosomal disorder

Gaucher's disease type 3, Niemann-Pick disease type C

Stroke, stroke-like episodes

Mitochondrial disorder

Electron transport chain defects

 

Lysosomal disorder

Fabry's disease

 

Defect in amino acid metabolism

Homocystinuria, methylene tetrahydrofolate reductase deficiency

 

Defect in urea cycle

Ornithine transcarbamylase deficiency

Recurrent attacks of ataxia

Mitochondrial disorder

Pyruvate dehydrogenase deficiency, electron transport chain defects

 

Defect in amino acid metabolism

Branched-chain organic aciduria, methylene tetrahydrofolate reductase deficiency

 

Defect in urea cycle

Ornithine transcarbamylase deficiency

Recurrent psychiatric symptoms

Defect in amino acid metabolism

Methylene tetrahydrofolate reductase deficiency

 

Organic acid disorder

Branched-chain organic acid disorder

 

Defect in urea cycle

Ornithine transcarbamylase deficiency

 

Defect in heme biosynthesis

Acute porphyria