UNASSIGNED: Mitochondrial @entity2453 synthase (HMCS2) deficiency results in episodes of @entity4053 and increases in @entity844 metabolites. @entity854 described to date in @entity942 are nonspecific and overlap with other @entity2246 , making the biochemical diagnosis of @entity942 difficult. Urinary organic acid profiles from periods of metabolic decompensation were studied in detail in @entity942 @entity1 from four families. An additional six unrelated @entity1 were identified from clinical presentation and/or qualitative identification of abnormal organic acids. The diagnosis was confirmed by sequencing and deletion/duplication analysis of the @entity29536 gene. Seven related novel organic acids were identified in urine profiles. Five of them (3,5-dihydroxyhexanoic 1,5 @entity13629 ; trans-5-hydroxyhex-2-enoate; @entity68724 ; 5-hydroxy-3-ketohexanoate; 3,5-dihydroxyhexanoate) were identified by comparison with synthesized or commercial authentic compounds. We provisionally identified trans-3-hydroxyhex-4-enoate and @entity68725 by their mass spectral characteristics. These metabolites were found in samples taken during periods of decompensation and normalized when @entity1 recovered. When cutoffs of adipic >200 and @entity68724 >20   mol/mmol @entity1011 were applied, all eight samples taken from five @entity942 @entity1 during episodes of decompensation were flagged with a positive predictive value of 80  % (95  % confidence interval 35-100  %). Some ketotic @entity1 had increased @entity68724 . Molecular studies identified a total of 12 novel mutations, including a large deletion of @entity29536 exon 1 in two families, highlighting the need to perform quantitative gene analyses. There are now 26 known @entity29536 mutations, which are reviewed in the text. @entity68724 and related metabolites are markers for @entity942 . Detection of these metabolites will streamline the biochemical diagnosis of this disorder.

Mitochondrial XXXX synthase deficiency: urinary organic acid profiles and expanded spectrum of mutations.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity29536 :: ('3158', 'Gene') :: ['HMGCS2'] @entity844 :: ('CHEBI:35366', 'Chemical') :: ['fatty acid'] @entity4053 :: ('MESH:D007003', 'Disease') :: ['hypoglycemia'] @entity68725 :: ('CHEBI:20051', 'Chemical') :: ['3-hydroxy-5-ketohexanoate'] @entity68724 :: ('MESH:C525072', 'Chemical') :: ['4-hydroxy-6-methyl-2-pyrone', '4-Hydroxy-6-methyl-2-pyrone'] @entity854 :: ('MESH:D018376', 'Disease') :: ['Metabolite abnormalities'] @entity13629 :: ('CHEBI:25000', 'Chemical') :: ['lactone'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine'] @entity2453 :: ('MESH:C008047', 'Chemical') :: ['3-hydroxy-3-methylglutaryl CoA'] @entity942 :: ('MESH:D003677', 'Disease') :: ['HMCS2-deficient', 'HMCS2 deficiency'] @entity2246 :: ('MESH:D008661', 'Disease') :: ['inborn errors of metabolism']
@entity2453 :: (MESH:C008047,Chemical) :: ['3-hydroxy-3-methylglutaryl-CoA']
