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Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency.
J Inherit Metab Dis. 2006 Feb; 29(1):207-11.JI

Abstract

Mitochondrial HMG-CoA synthase deficiency is an inherited metabolic disorder caused by a defect in the enzyme that regulates the formation of ketone bodies. Patients present with hypoketotic hypoglycaemia, encephalopathy and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting. The diagnosis may easily be missed as previously reported results of routine metabolic investigations, urinary organic acids and plasma acylcarnitines may be nonspecific or normal, and a high index of suspicion is required to proceed to further confirmatory tests. We describe a further acute case in which the combination of urinary organic acids, low free carnitine and changes in the plasma acylcarnitine profile on carnitine supplementation were very suggestive of a defect in ketone synthesis. The diagnosis of mitochondrial HMG-CoA synthase deficiency was confirmed on genotyping, revealing two novel mutations: c.614G > A (R188H) and c.971T > C (M307T). A further sibling, in whom the diagnosis had not been made acutely, was also found to be affected. The possible effects of these mutations on enzyme activity are discussed.

Authors+Show Affiliations

Unit of Biochemistry and Molecular Biology, School of Health Sciences, International University of Catalonia, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16601895

Citation

Aledo, R, et al. "Refining the Diagnosis of Mitochondrial HMG-CoA Synthase Deficiency." Journal of Inherited Metabolic Disease, vol. 29, no. 1, 2006, pp. 207-11.
Aledo R, Mir C, Dalton RN, et al. Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency. J Inherit Metab Dis. 2006;29(1):207-11.
Aledo, R., Mir, C., Dalton, R. N., Turner, C., Pié, J., Hegardt, F. G., Casals, N., & Champion, M. P. (2006). Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency. Journal of Inherited Metabolic Disease, 29(1), 207-11.
Aledo R, et al. Refining the Diagnosis of Mitochondrial HMG-CoA Synthase Deficiency. J Inherit Metab Dis. 2006;29(1):207-11. PubMed PMID: 16601895.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency. AU - Aledo,R, AU - Mir,C, AU - Dalton,R N, AU - Turner,C, AU - Pié,J, AU - Hegardt,F G, AU - Casals,N, AU - Champion,M P, PY - 2006/4/8/pubmed PY - 2006/10/17/medline PY - 2006/4/8/entrez SP - 207 EP - 11 JF - Journal of inherited metabolic disease JO - J Inherit Metab Dis VL - 29 IS - 1 N2 - Mitochondrial HMG-CoA synthase deficiency is an inherited metabolic disorder caused by a defect in the enzyme that regulates the formation of ketone bodies. Patients present with hypoketotic hypoglycaemia, encephalopathy and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting. The diagnosis may easily be missed as previously reported results of routine metabolic investigations, urinary organic acids and plasma acylcarnitines may be nonspecific or normal, and a high index of suspicion is required to proceed to further confirmatory tests. We describe a further acute case in which the combination of urinary organic acids, low free carnitine and changes in the plasma acylcarnitine profile on carnitine supplementation were very suggestive of a defect in ketone synthesis. The diagnosis of mitochondrial HMG-CoA synthase deficiency was confirmed on genotyping, revealing two novel mutations: c.614G > A (R188H) and c.971T > C (M307T). A further sibling, in whom the diagnosis had not been made acutely, was also found to be affected. The possible effects of these mutations on enzyme activity are discussed. SN - 0141-8955 UR - https://www.unboundmedicine.com/medline/citation/16601895/Refining_the_diagnosis_of_mitochondrial_HMG_CoA_synthase_deficiency_ L2 - https://doi.org/10.1007/s10545-006-0214-2 DB - PRIME DP - Unbound Medicine ER -