3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency


3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (3-Hydroxy-3-methylglutaric acidemia; Leucine metabolism, defect in, HMG-CoA lyase deficiency) is an autosomal recessive disease caused by a mutation in the HMGCL gene which codes for hydroxymethylglutaryl-CoA lyase. A deficiency in this enzyme results in accumulation of 3-hydroxymethylglutaric acid, 3-hydroxyisovaleric acid, 3-methylcrotonylglycine and 3-methylglutaconic acid (cis and trans form), and methylglutaric acid in urine; and ammonia in blood. Symptoms include cardiomyopathy, dehydration, hypotonia, lactic acidosis, and pancreatitis. Treatment includes a low-fat, low-protein, high-carbohydrate diet.

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References

  1. Wikipedia: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
  2. Uniprot: P35914
  3. OMIM: Entry 246450
  4. Barash V, Mandel H, Sella S, Geiger R: 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: biochemical studies and family investigation of four generations. J Inherit Metab Dis. 1990;13(2):156-64. Pubmed
  5. Faull KF, Bolton PD, Halpern B, Hammond J, Danks DM: The urinary organic acid profile associated with 3-hydroxy-3-methylglutaric aciduria. Clin Chim Acta. 1976 Dec;73(3):553-9. Pubmed
  6. Muroi J, Yorifuji T, Uematsu A, Shigematsu Y, Onigata K, Maruyama H, Nobutoki T, Kitamura A, Nakahata T: Molecular and clinical analysis of Japanese patients with 3-hydroxy-3-methylglutaryl CoA lyase (HL) deficiency. Hum Genet. 2000 Oct;107(4):320-6. Pubmed
  7. Mitchell GA, Robert MF, Hruz PW, Wang S, Fontaine G, Behnke CE, Mende-Mueller LM, Schappert K, Lee C, Gibson KM, Miziorko HM, et al.: 3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human and chicken liver HL cDNAs and characterization of a mutation causing human HL deficiency. J Biol Chem. 1993 Feb 25;268(6):4376-81. Pubmed