Inborn errors of metabolism as a cause of neurological disease in adults: an approach to investigation

• Published in: Journal of neurology, neurosurgery and psychiatry neurosurgery and psychiatry, 2000-07, Vol.69 (1), p.5-12
• Main Authors: Gray, R G F, Preece, M A, Green, S H, Whitehouse, W, Winer, J, Green, A
• Format: Article
• Language: English
• Subjects: Adult; Adults; Age; Amino acids; Ammonia; Ataxia; Biological and medical sciences; Biopsy; Bone marrow; Brain Diseases, Metabolic, Inborn - diagnosis; Brain Diseases, Metabolic, Inborn - genetics; Cardiomyopathy; Cognitive ability; Coma; Defects; Dementia; Enzymes; Fibroblasts; Humans; Laboratories; Liver diseases; Medical sciences; Metabolic disorders; Metabolism, Inborn Errors - diagnosis; Metabolism, Inborn Errors - genetics; Metabolites; Mitochondrial DNA; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Plasma; Psychosis; Review; Urine
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.69.1.5

Disease Clinical symptoms Tests Lysosomal storage diseases - Acid maltase deficiency Muscle weakness, respiratory difficulty Lymphocyte [alpha]-glucosidase - Fabry's disease Peripheral nerve pain (+-renal failure+-angiokeratoma+-cardiomyopathy), stroke-like episodes Leucocyte [alpha]-galactosidase A - Gaucher's disease type III Horizontal supranuclear gaze defect, developmental delay, hydrocephalus, skeletal abnormalities, psychosis Leucocyte [beta]-glucosidase, bone marrow aspirate - GM1 gangliosidosis (i) Extra pyramidal signs, flattening of vertebral bodies, normal cognitive function. sometimes with psychosis Leucocyte [beta]-galactosidase, urine oligosaccharides - GM2 gangliosidosis (Tay Sach's and Sandhoff's disease) (i) Lower motor neuron disease with onset 20-40 y, pyramidal signs, and cerebellar degeneration Leucocyte total, hexosaminidase, and hexosaminidase A (ii) Atypical amyotropic lateral sclerosis - Krabbe's leukodystrophy Pes cavus, hemiparesis, spastic tetraparesis, leukodystrophy Leucocyte [beta]-galactocerebrosidase - Metachromatic leukodystrophy Loss of cognitive function or behavioural abnormalities, neuromuscular weakness with impaired nerve conduction, leukodystrophy Leucocyte arylsulphatase A (the pseudodeficiency state must be excluded) - Sialidosis (mucolipidosis type I) Type I Urine oligosaccharides, fibroblast [alpha]-neuraminidase Visual defect with lens or corneal opacity, ataxia, myoclonus, generalised seizures sometimes with nystagmus, ataxia Type II Dementia+-cherry red spot Myoclonus, blindness, cherry red spot, dysmorphic features, angiokeratoma. - Plasma very long chain fatty acids. (ii) Onset >30 y in females, spastic paraparesis, vibratory sense loss, long tract signs, peripheral neuropathy Lactic acidaemias Electron transport chain disorders (i) mtDNA encoded NARP, MELAS, MERRF, Kearns-Sayre syndrome, LHON Blood or tissue mtDNA analysis - (ii) Nuclear DNA encoded Muscle weakness, multisystem disease CSF/plasma lactate, muscle biopsy for respiratory chain assays Disorders of the glycogenolytic and glycolytic pathway - Glycogen storage diseases Muscle weakness, cardiomyopathy, hepatomegaly, hypoglycaemia, myopathy Muscle enzyme assays, but many of the glycogen storage diseases can be diagnosed by leucocyte or erythrocyte enzyme assays - Glycolytic pathway disorders Muscle weakness (second wind phenomenon), exercise intolerance, myoglobinuria Muscle enzyme assays, but many of the glycolytic disorders can be diagnosed by e