تقرير
أعرض في EDS

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.

التفاصيل البيبلوغرافية
العنوان: 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.
المؤلفون: Conlon TA; National Centre for Inherited Metabolic Disorders Children's Health Ireland at Temple Street Dublin Ireland.; School of Medicine University College Dublin Dublin Ireland., Fitzsimons PE; Department of Paediatric Laboratory Medicine Children's Health Ireland at Temple Street Dublin Ireland., Borovickova I; Department of Paediatric Laboratory Medicine Children's Health Ireland at Temple Street Dublin Ireland., Kirby F; Department of Paediatric Intensive Care Children's Health Ireland at Temple Street Dublin Ireland., Murphy S; School of Medicine University College Dublin Dublin Ireland.; Department of General Paediatrics Children's Health Ireland at Temple Street Dublin Ireland., Knerr I; National Centre for Inherited Metabolic Disorders Children's Health Ireland at Temple Street Dublin Ireland.; School of Medicine University College Dublin Dublin Ireland., Crushell E; National Centre for Inherited Metabolic Disorders Children's Health Ireland at Temple Street Dublin Ireland.; School of Medicine University College Dublin Dublin Ireland.
المصدر: JIMD reports [JIMD Rep] 2020 Jun 30; Vol. 55 (1), pp. 26-31. Date of Electronic Publication: 2020 Jun 30 (Print Publication: 2020).
نوع المنشور: Case Reports
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: United States NLM ID: 101568557 Publication Model: eCollection Cited Medium: Print ISSN: 2192-8304 (Print) Linking ISSN: 21928304 NLM ISO Abbreviation: JIMD Rep Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2019- : [Hoboken, NJ] : Wiley
Original Publication: Berlin : SSIEM and Springer-Verlag, c2011.
مستخلص: 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.
Competing Interests: 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.
(© 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)
References: Lab Res Methods Biol Med. 1981;6:1-158. (PMID: 6820455)
JIMD Rep. 2018;40:63-69. (PMID: 29030856)
J Chromatogr A. 1999 Jun 4;844(1-2):1-22. (PMID: 10399322)
JIMD Rep. 2019 Jun 03;48(1):19-25. (PMID: 31392109)
J Inherit Metab Dis. 2014 Jul;37(4):541-51. (PMID: 24706027)
J Pediatr. 2002 Jun;140(6):778-80. (PMID: 12072887)
Hum Genet. 2001 Jul;109(1):19-23. (PMID: 11479731)
JIMD Rep. 2020 Jun 30;55(1):26-31. (PMID: 32905056)
Int J Mol Sci. 2018 Mar 28;19(4):. (PMID: 29597274)
J Inherit Metab Dis. 2012 Jan;35(1):23-8. (PMID: 21479626)
J Inherit Metab Dis. 2006 Feb;29(1):207-11. (PMID: 16601895)
Pediatr Res. 2001 Mar;49(3):326-31. (PMID: 11228257)
Eur J Med Genet. 2013 Aug;56(8):411-5. (PMID: 23751782)
N Engl J Med. 1997 Oct 23;337(17):1203-7. (PMID: 9337379)
J Inherit Metab Dis. 2015 May;38(3):459-66. (PMID: 25511235)
Clin Chem. 2003 Nov;49(11):1797-817. (PMID: 14578311)
Eur J Pediatr. 2003 Apr;162(4):279-80. (PMID: 12647205)
Pediatr Res. 2006 Feb;59(2):196-202. (PMID: 16439578)
Pediatr Res. 1998 Sep;44(3):392-6. (PMID: 9727719)
فهرسة مساهمة: Keywords: 3‐hydroxyglutarate (3HG); 4‐hydroxy‐6‐methyl‐2‐pyrone (4HMP); HMG‐CoA synthase deficiency; hypertriglyceridemia; hypoglycemia; ketogenesis
تواريخ الأحداث: Date Created: 20200909 Latest Revision: 20240329
رمز التحديث: 20240329
مُعرف محوري في PubMed: PMC7463059
DOI: 10.1002/jmd2.12146
PMID: 32905056
قاعدة البيانات: MEDLINE
الوصف
تدمد:2192-8304
DOI:10.1002/jmd2.12146