Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG Co-A) synthase (mHS) deficiency is an autosomal recessive disorder of ketone body synthesis which has traditionally been associated with hypoketotic hypoglycemia, hepatomegaly and encephalopathy, presenting in early childhood following a period of fasting. We report the third case of mHS deficiency presenting in the absence of hypoglycemia, with profound biochemical abnormalities and further evidence of potential specific diagnostic biomarkers. A previously well, 20-month old, unvaccinated male, of nonconsanguineous Polish heritage, presented with encephalopathy, hepatomegaly, severe metabolic acidosis, and mild hyperammonemia following a brief intercurrent illness. The patient was reported to have taken colloidal silver prior to presentation, posing a further diagnostic challenge. Additionally, he developed features suggestive of hemophagocytic lymphohistiocytosis during treatment. While the patient was normoglycemic prior to dextrose administration, the sample was markedly lipemic, with significant hypertriglyceridemia detected. Urine organic acid analysis revealed dicarboxylic aciduria with 4-hydroxy-6-methyl-2-pyrone (4HMP) and the presence of three other previously reported putative biomarkers for mHS deficiency. Glutarate was markedly elevated in the initial chromatogram, with a mild increase in 3-hydroxyglutarate (3HG) persisting. Raised acetylcarnitine was detected on acylcarnitine profile. Molecular genetic analysis of the HMGCS2 gene identified compound heterozygosity for known pathogenic mutations c.634G>A and c.1016+1G>A, confirming the diagnosis of mHS deficiency. This case provides further evidence that hypoglycemia is not invariably present in symptomatic mHS deficiency. We propose that elevated acetylcarnitine, triglycerides, and 3HG are additional biochemical features during acute presentations. With the expansion of novel biomarkers, further cases of this rare disorder may emerge.
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PMID:Hypoglycemia is not a defining feature of metabolic crisis in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: Further evidence of specific biochemical markers which may aid diagnosis. 3290 56