Inherited metabolic disorders with adult onset forms
| Disease | Clinical symptoms | Tests | ||
| Lysosomal storage diseases | ||||
| Acid maltase deficiency | Muscle weakness, respiratory difficulty | Lymphocyte α-glucosidase | ||
| Fabry's disease | Peripheral nerve pain (±renal failure±angiokeratoma±cardiomyopathy), stroke-like episodes | Leucocyte α-galactosidase A | ||
| Gaucher's disease type III | Horizontal supranuclear gaze defect, developmental delay, hydrocephalus, skeletal abnormalities, psychosis | Leucocyte β-glucosidase, bone marrow aspirate | ||
| GM1 gangliosidosis | (i) Extra pyramidal signs, flattening of vertebral bodies, normal cognitive function. sometimes with psychosis | Leucocyte β-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 β-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 α-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. | ||||
| Niemann-Pick's disease type C | Psychomotor retardation leading to dementia, ataxia with dystonia | Bone marrow aspirate, fibroblast cholesterol uptake and staining. | ||
| Amino acid disorders | ||||
| Arginase deficiency | Disorientation, coma | Plasma and urine amino acids, plasma ammonia (1 h postprandial). | ||
| Citrullinaemia | Disorientation, restlessness, coma | Plasma and urine amino acids, plasma ammonia (1 h postprandial). | ||
| Hartnup's disease | Dementia, ataxia ±skin lesions. | Plasma and urine amino acids | ||
| Homocystinuria (cystathionine synthasedeficiency: classic form) | Occlusive cerebrovascular disease, dislocated lenses, osteoporosis, psychiatric disturbances | Urine homocystine, plasma homocystine and methionine | ||
| Homocystinuria (methylene tetrahydrofolatereductase deficiency remethylation defect). | Parasthaesia, hallucinations, tremor, withdrawal, mental retardation, limb weakness, memory loss | Urine homocystine, plasma homocystine and methionine | ||
| Hyperornithinaemiawith gyrate atrophy of the retina | Gyrate atrophy of choroid and retina | Plasma and urine amino acids (ornithine) | ||
| Ornithine transcarbamylase deficiency | Behavioural disturbances, comatose episodes, sleep disorders | Plasma ammonia (1 h postprandial)plasma amino acids, urine amino acids and orotic acid | ||
| Organic acid disorders | ||||
| Fatty acid oxidation defects | Muscle weakness, easy fatigability ±liver disease ±cardiomyopathy ±hypoglycaemia | Urine organic acids (fasting) | ||
| Glutaric aciduria type 1 | Dystonia±hypoglycaemia, may present with a Reye-like syndrome | Urine organic acids, blood spot acyl carnitines | ||
| Propionic acidaemia | Chorea and dementia, recurrent vomiting | Urine organic acids, blood spot acyl carnitines | ||
| Peroxisomal disorders | ||||
| X linked adrenoleukodystrophy | (i) Onset 20–30 y in males, gait disturbance, spastic paraparesis, intellectual function usually intact, impotence±Addison's disease, occasionally cerebral symptoms may occur, eg dementia and psychosis. | 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 erythrocyte enzyme assay | ||
| ± haemolytic anaemia | ||||
| Other disorders | ||||
| Abetalipoproteinaemia | Ataxia, retinitis pigmentosa | Plasma cholesterol, blood film (acanthocytes), lipoproteins | ||
| Acaeruloplasminaemia | Ataxia, retinal dystrophy±diabetes mellitus±presenile dementia | Plasma and urine copper, plasma iron and ferritin | ||
| Adult polyglucosan body disease | Upper and lower motor neuron signs, sensory loss, neurogenic bladder, dementia | Leucocyte glycogen brancher enzyme (some forms may show normal muscle activity). | ||
| Cerebrotendinous xanthomatosis | Spasticity, ataxia, cataracts, tendon xanthomas | Urine bile alcohols | ||
| Hereditary vitamin E deficiency | Tremor, ataxia, head titubation, loss of vibration sense. | Plasma vitamin E, plasma cholesterol and triglycerides | ||
| Homocystinuria and methylmalonic aciduria (combined defect) | Megaloblastic anaemia, dystonia | Urine organic acids and homocystine | ||
| Juvenile Batten's disease | Seizures, visual loss, dementia | Skin or rectal biopsy for histological analysis, DNA analysis for the common mutation | ||
| Kuf's disease | Type A | Skin or rectal biopsy for histological analysis | ||
| Progressive myoclonic epilepsy | ||||
| Type B | ||||
| Motor problems, psychosis, dementia | ||||
| Lesch-Nyhan syndrome | Some forms may present late with choreiform movements, dysarthria ± renal problems | Plasma urate and urine,urate/creatinine | ||
| Porphyrias | Limb, neck, and chest pain, muscle weakness, sensory loss, seizures,behavioural abnormalities±abdominal symptoms±photosensitivity | Urine delta amino laevulinic acid and porphobilinogen, urine and fecal porphyrins | ||
| Pyridoxine responsive seizures | Persistent seizures responsive to pyridoxine | In vivo pyridoxine response test: primary defect not known | ||
| Refsum's disease | Retinitis pigmentosa, peripheral polyneuropathy, cerebellar ataxia | Plasma phytanic acid | ||
| Segawa disease | Cyclical dystonia | Levodopa trial (some forms have a defect in biopterin metabolism) | ||
| Sjogren-Larrson syndrome | Spastic tetraplegia ±ichthyosis, mental retardation | Fibroblast fatty alcohol, oxidoreductase assay | ||
| Wilson's disease | Dysarthria, loss of coordination of voluntary movements, pseudobulbar palsy, parkinsonian features, renal failure, liver disease, Kayser-Fleischer rings, dementia | Urine copper (pre and postpenicillamine) | ||
| Plasma copper and caeruloplasmin | ||||