Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homozygous deficiency of aminolaevulinate dehydratase (porphobilinogen synthase, EC 4.2.1.24) was diagnosed in a small child. The clinical presentation was unique since severe symptoms were already present in the neonatal period. The patient, a boy, now three-years old, had recurrent attacks of pain, vomiting, hyponatraemia and symptoms of polyneuropathy engaging motor functions including respiration. The clinical course of the disease from birth on is related, as are the results of various attempts at therapy. The patient excreted large amounts of 5-aminolaevulinic acid and coproporphyrin and minor amounts of porphobilinogen in the urine. Faecal excretion of coproporphyrin and harderoporphyrin was increased as was erythrocyte porphyrin concentration. Diagnosis was established by the finding that erythrocyte aminolaevulinate dehydratase activity was less than 5 per cent of normal in the patient and between 26 and 51 per cent of normal in both the parents, the grandfathers and a sibling. The activity of the enzyme could not be restored by the addition of dithiothreitol (10(-3) mol/l) alone, or in combination with zinc or manganese in varying concentrations. The enzyme Km did not differ between affected and nonaffected members of the family.
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PMID:Aminolaevulinate dehydratase porphyria in infancy. A clinical and biochemical study. 355 84

Four types of hepatic porphyria (acute intermittent porphyria; hereditary coprophorphyria; variegate porphyria; delta-aminolevulinate dehydratase deficiency porphyria) present clinically with an identical neurological syndrome. Symptoms include severe abdominal pain, vomiting, constipation, hypertension, tachycardia, and bladder dysfunction. These symptoms have been ascribed to autonomic neuropathy. Other symptoms are motor weakness and sensory involvement, which correlate with peripheral axonal neuropathy, and mental symptoms occurring without clear morphological findings in the cerebrum. The pathogenetic mechanisms which lead to the neurological dysfunction have remained poorly understood, partly due to the lack of a suitable animal model of these rare disorders. Two hypotheses, the possible neurotoxicity of delta-aminolevulinate (ALA) and heme deficiency in nervous tissue are discussed and corresponding data from porphobilinogen-deaminase deficient mice are presented. The present evidence suggests that multiple mechanisms interact in causing the varied symptoms, including ALA interaction with GABA receptors, altered tryptophan metabolism, and possibly heme depletion in nerve cells.
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PMID:Acute porphyrias: pathogenesis of neurological manifestations. 951 77