3-hydroxy-3-methylglutaryl-CoA lyase deficiency
Last updated 26 Jul 2023
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3-hydroxy-3-methylglutaryl-CoA lyase deficiency (also known as HMG-CoA lyase deficiency) is an uncommon inherited disorder in which the body cannot process a particular protein building block (amino acid) called leucine. Additionally, the disorder prevents the body from making ketones, which are compounds that are used for energy during periods without food (fasting).
Description
3-hydroxy-3-methylglutaryl-CoA lyase deficiency (also known as HMG-CoA lyase deficiency) is an uncommon inherited disorder in which the body cannot process a particular protein building block (amino acid) called leucine. Additionally, the disorder prevents the body from making ketones, which are compounds that are used for energy during periods without food (fasting).
The signs and symptoms of HMG-CoA lyase deficiency usually appear within the first year of life. The condition causes episodes of vomiting, diarrhea, dehydration, extreme tiredness (lethargy), and weak muscle tone (hypotonia). During an episode, blood sugar (glucose) levels can become dangerously low (hypoglycemia), and a buildup of harmful compounds can cause the blood to become too acidic (metabolic acidosis). If untreated, the disorder can lead to breathing problems, convulsions, coma, and death. Episodes are often triggered by an infection, fasting, strenuous exercise, or other types of stress.
HMG-CoA lyase deficiency is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.
Inheritance patterns
The source lists the following possible inheritance patterns: Autosomal recessive. More than one pattern can apply in different cases.
Related genes
Other names
3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency
3-OH 3-CH3 glutaric aciduria
3-OH 3-methyl glutaric aciduria
3HMG
Deficiency of hydroxymethylglutaryl-CoA lyase
HMG
HMG-CoA lyase deficiency
Hydroxymethylglutaric aciduria
Further reading and references
- 3-hydroxy-3-methylglutaryl-CoA lyase deficiency; MedlinePlus, National Library of Medicine.
- Bischof F, Nagele T, Wanders RJ, Trefz FK, Melms A. 3-hydroxy-3-methylglutaryl-CoA lyase deficiency in an adult with leukoencephalopathy. Ann Neurol. 2004 Nov;56(5):727-30. doi: 10.1002/ana.20280.
- Casals N, Gomez-Puertas P, Pie J, Mir C, Roca R, Puisac B, Aledo R, Clotet J, Menao S, Serra D, Asins G, Till J, Elias-Jones AC, Cresto JC, Chamoles NA, Abdenur JE, Mayatepek E, Besley G, Valencia A, Hegardt FG. Structural (betaalpha)8 TIM barrel model of 3-hydroxy-3-methylglutaryl-coenzyme A lyase. J Biol Chem. 2003 Aug 1;278(31):29016-23. doi: 10.1074/jbc.M304276200. Epub 2003 May 13.
- Gibson KM, Breuer J, Nyhan WL. 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients. Eur J Pediatr. 1988 Dec;148(3):180-6. doi: 10.1007/BF00441397.
- Mitchell GA, Ozand PT, Robert MF, Ashmarina L, Roberts J, Gibson KM, Wanders RJ, Wang S, Chevalier I, Plochl E, Miziorko H. HMG CoA lyase deficiency: identification of five causal point mutations in codons 41 and 42, including a frequent Saudi Arabian mutation, R41Q. Am J Hum Genet. 1998 Feb;62(2):295-300. doi: 10.1086/301730.
- Pie J, Casals N, Puisac B, Hegardt FG. Molecular basis of 3-hydroxy-3-methylglutaric aciduria. J Physiol Biochem. 2003 Dec;59(4):311-21. doi: 10.1007/BF03179889.
- Pie J, Lopez-Vinas E, Puisac B, Menao S, Pie A, Casale C, Ramos FJ, Hegardt FG, Gomez-Puertas P, Casals N. Molecular genetics of HMG-CoA lyase deficiency. Mol Genet Metab. 2007 Nov;92(3):198-209. doi: 10.1016/j.ymgme.2007.06.020. Epub 2007 Aug 9.
- Yalcinkaya C, Dincer A, Gunduz E, Ficicioglu C, Kocer N, Aydin A. MRI and MRS in HMG-CoA lyase deficiency. Pediatr Neurol. 1999 May;20(5):375-80. doi: 10.1016/s0887-8994(99)00013-2.
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