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)

3-Hydroxy-3-methylglutaric aciduria (OMIM 246450) is an autosomal recessive inborn error of the final step of leucine catabolic and ketogenic pathways, caused by deficiency of the enzyme 3-hydroxy-3-methylglutaryl CoA lyase (HL, HMGCL, EC 4.1.3.4). Clinically, deficiency of the enzyme results in metabolic acidosis, hyperammonemia, and infantile hypoketotic hypoglycaemia usually presenting during the first year of life with vomiting, lethargy, hypotonia, and sometimes with respiratory distress and coma. HL deficiency is relatively common in Arabic populations but seems to be rare in Europe. Our recent experience suggests that HL deficiency is the most frequent organic aciduria in the Portuguese population. We herein report on the molecular study of the HMGCL gene in 11 cases originated from the Northern area of Portugal. We detected the E37X (c.109G > T) mutation, in 84.1% of the alleles, one allele carried the V168fs(-2) (504_505delCT) and other allele the novel D204N (c.610G > A) mutation. The mutation of the last allele remained unidentified. The relatively high frequency of the "common" HMGCL Portuguese mutation makes useful the development of a rapid and specific molecular confirmation of new cases with HL deficiency in our country.
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PMID:The E37X is a common HMGCL mutation in Portuguese patients with 3-hydroxy-3-methylglutaric CoA lyase deficiency. 1530 32

3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic disorder that affects ketogenesis and L-leucine catabolism. The clinical acute symptoms include vomiting, convulsions, metabolic acidosis, hypoketotic hypoglycaemia and lethargy. To date, 33 mutations in 100 patients have been reported in the HMGCL gene. In this study 10 new mutations in 24 patients are described. They include: 5 missense mutations: c.109G>A, c.425C>T, c.521G>A, c.575T>C and c.598A>T, 2 nonsense mutations: c.242G>A and c.559G>T, one small deletion: c.853delC, and 2 mutations in intron regions: c.497+4A>G and c.750+1G>A. Two prevalent mutations were detected, 109G>T (E37X) in 38% of disease alleles analyzed and c.504_505delCT in 10% of them. Although patients are mainly of European origin (71%) and mostly Spanish (54%), the group is ethnically diverse and includes, for the first time, patients from Pakistan, Palestine and Ecuador. We also present a simple, efficient method to express the enzyme and we analyze the possible functional effects of missense mutations. The finding that all identified missense mutations cause a >95% decrease in the enzyme activity, indicates that the disease appears only in very severe genotypes."
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PMID:Ten novel HMGCL mutations in 24 patients of different origin with 3-hydroxy-3-methyl-glutaric aciduria. 1917 31