The E37X is a common HMGCL mutation in Portuguese patients with 3-hydroxy-3-methylglutaric CoA lyase deficiency

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 met...

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Bibliographic Details
Published in:Molecular genetics and metabolism 2004-08, Vol.82 (4), p.334-338
Main Authors: Cardoso, M.L, Rodrigues, M.R, Leão, E, Martins, E, Diogo, L, Rodrigues, E, Garcia, P, Rolland, M.O, Vilarinho, L
Format: Article
Language:English
Subjects:
3-Hydroxy-3-methylglutaryl CoA lyase
Acidosis - ethnology
Acidosis - genetics
Alleles
E37X mutation
European Continental Ancestry Group - genetics
HMGCL
Humans
Hyperammonemia - ethnology
Hyperammonemia - genetics
Metabolic disorders, 3-Hydroxy-3-methylglutaric aciduria
Oxo-Acid-Lyases - deficiency
Oxo-Acid-Lyases - genetics
Point Mutation - genetics
Portugal
Syndrome
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Summary: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.
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2004.06.003