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.
3‐hydroxyglutarate (3HG)
4‐hydroxy‐6‐methyl‐2‐pyrone (4HMP)
HMG‐CoA synthase deficiency
hypertriglyceridemia
hypoglycemia
ketogenesis
Journal
JIMD reports
ISSN: 2192-8304
Titre abrégé: JIMD Rep
Pays: United States
ID NLM: 101568557
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
17
12
2019
revised:
25
05
2020
accepted:
27
05
2020
entrez:
9
9
2020
pubmed:
10
9
2020
medline:
10
9
2020
Statut:
epublish
Résumé
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
Identifiants
pubmed: 32905056
doi: 10.1002/jmd2.12146
pii: JMD212146
pmc: PMC7463059
doi:
Types de publication
Case Reports
Langues
eng
Pagination
26-31Informations de copyright
© 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.
Déclaration de conflit d'intérêts
Tracey A. Conlon, Patricia E. Fitzsimons, Ingrid Borovickova, Fidelma Kirby, Sinéad Murphy, Ina Knerr, and Ellen Crushell declare that they have no conflicts of interest pertaining to the manuscript.
Références
Lab Res Methods Biol Med. 1981;6:1-158
pubmed: 6820455
JIMD Rep. 2018;40:63-69
pubmed: 29030856
J Chromatogr A. 1999 Jun 4;844(1-2):1-22
pubmed: 10399322
JIMD Rep. 2019 Jun 03;48(1):19-25
pubmed: 31392109
J Inherit Metab Dis. 2014 Jul;37(4):541-51
pubmed: 24706027
J Pediatr. 2002 Jun;140(6):778-80
pubmed: 12072887
Hum Genet. 2001 Jul;109(1):19-23
pubmed: 11479731
Int J Mol Sci. 2018 Mar 28;19(4):
pubmed: 29597274
J Inherit Metab Dis. 2012 Jan;35(1):23-8
pubmed: 21479626
J Inherit Metab Dis. 2006 Feb;29(1):207-11
pubmed: 16601895
Pediatr Res. 2001 Mar;49(3):326-31
pubmed: 11228257
Eur J Med Genet. 2013 Aug;56(8):411-5
pubmed: 23751782
N Engl J Med. 1997 Oct 23;337(17):1203-7
pubmed: 9337379
J Inherit Metab Dis. 2015 May;38(3):459-66
pubmed: 25511235
Clin Chem. 2003 Nov;49(11):1797-817
pubmed: 14578311
Eur J Pediatr. 2003 Apr;162(4):279-80
pubmed: 12647205
Pediatr Res. 2006 Feb;59(2):196-202
pubmed: 16439578
Pediatr Res. 1998 Sep;44(3):392-6
pubmed: 9727719