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Refining the diagnosis of mitochondrial HMG‐CoA synthase deficiency
Author(s) -
Aledo R.,
Mir C.,
Dalton R. N.,
Turner C.,
Pié J.,
Hegardt F. G.,
Casals N.,
Champion M. P.
Publication year - 2006
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-006-0214-2
Subject(s) - carnitine , ketone bodies , endocrinology , medicine , atp synthase , urinary system , propionic acidemia , newborn screening , mitochondrial disease , enzyme , biology , biochemistry , metabolism , mitochondrial dna , gene
Summary 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.