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A Japanese case of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency who presented with severe metabolic acidosis and fatty liver without hypoglycemia.
JIMD Rep. 2019 Jul; 48(1):19-25.JR

Abstract

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mHS deficiency) is a rare autosomal recessive inborn error of ketogenesis caused by a mutation in the HMGCS2 gene, which is characterized by non-(hypo)-ketotic hypoglycemia, lethargy, and hepatomegaly during acute infection and/or prolonged fasting. Clinical presentations are similar to fatty acid oxidation defects; however, diagnosis of mHS deficiency is difficult because of poor biochemical markers. We report the case of a 12-month-old Japanese boy with mHS deficiency who presented with a coma, and hepatomegaly, but no hypoglycemia after a febrile episode and poor oral intake. Metabolic acidosis and severe fatty liver were observed. Serum acylcarnitine analysis revealed a slightly decreased free carnitine (C0) level and an increased acetylcarnitine (C2) level. Urinary organic acid analysis revealed hypoketotic dicarboxylic aciduria, and increased excretions of glutarate, and, retrospectively, 4-hydroxy-6-methyl-2-pyrone. Although the patient did not present with hypoglycemia, the severe fatty liver and elevated free fatty acids to total ketone bodies ratio strongly suggested an inborn error of ketogenesis. In the analysis of the HMGCS2 gene, compound heterozygous mutations of c.130_131ins C (L44PfsX29) and c.1156_1157insC (L386PfsX73) were identified, which led to the diagnosis of mHS deficiency. He had recovered without any complication by the therapy, including intravenous glucose infusion. Unlike the previously reported cases of mHS deficiency, our case did not present with hypoglycemia and the fatty liver lasted over several months. mHS deficiency should be taken into consideration when a patient has severe metabolic acidosis and fatty liver with no or subtle ketosis, even without hypoglycemia.

Authors+Show Affiliations

Department of Pediatrics Hyogo College of Medicine Nishinomiya Japan.Department of Pediatrics Japanese Red Cross Society Himeji Hospital Himeji Japan.Department of Pediatrics Shimane University Faculty of Medicine Izumo Japan.Department of Pediatrics Shimane University Faculty of Medicine Izumo Japan.Department of Pediatrics Shimane University Faculty of Medicine Izumo Japan.Department of Pediatrics Graduate School of Medicine, Gifu University Gifu Japan.Department of Pediatrics Graduate School of Medicine, Gifu University Gifu Japan.Department of Pediatrics Hyogo College of Medicine Nishinomiya Japan.Department of Pediatrics Graduate School of Medicine, Gifu University Gifu Japan.

Pub Type(s)

Case Reports

Language

eng

PubMed ID

31392109

Citation

Lee, Tomoko, et al. "A Japanese Case of Mitochondrial 3-hydroxy-3-methylglutaryl-CoA Synthase Deficiency Who Presented With Severe Metabolic Acidosis and Fatty Liver Without Hypoglycemia." JIMD Reports, vol. 48, no. 1, 2019, pp. 19-25.
Lee T, Takami Y, Yamada K, et al. A Japanese case of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency who presented with severe metabolic acidosis and fatty liver without hypoglycemia. JIMD Rep. 2019;48(1):19-25.
Lee, T., Takami, Y., Yamada, K., Kobayashi, H., Hasegawa, Y., Sasai, H., Otsuka, H., Takeshima, Y., & Fukao, T. (2019). A Japanese case of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency who presented with severe metabolic acidosis and fatty liver without hypoglycemia. JIMD Reports, 48(1), 19-25. https://doi.org/10.1002/jmd2.12051
Lee T, et al. A Japanese Case of Mitochondrial 3-hydroxy-3-methylglutaryl-CoA Synthase Deficiency Who Presented With Severe Metabolic Acidosis and Fatty Liver Without Hypoglycemia. JIMD Rep. 2019;48(1):19-25. PubMed PMID: 31392109.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Japanese case of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency who presented with severe metabolic acidosis and fatty liver without hypoglycemia. AU - Lee,Tomoko, AU - Takami,Yuichi, AU - Yamada,Kenji, AU - Kobayashi,Hironori, AU - Hasegawa,Yuki, AU - Sasai,Hideo, AU - Otsuka,Hiroki, AU - Takeshima,Yasuhiro, AU - Fukao,Toshiyuki, Y1 - 2019/06/03/ PY - 2019/03/21/received PY - 2019/05/15/revised PY - 2019/05/15/accepted PY - 2019/8/9/entrez PY - 2019/8/9/pubmed PY - 2019/8/9/medline KW - HMG‐CoA synthase deficiency KW - fatty liver KW - glutarate KW - ketogenesis SP - 19 EP - 25 JF - JIMD reports JO - JIMD Rep VL - 48 IS - 1 N2 - Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency (mHS deficiency) is a rare autosomal recessive inborn error of ketogenesis caused by a mutation in the HMGCS2 gene, which is characterized by non-(hypo)-ketotic hypoglycemia, lethargy, and hepatomegaly during acute infection and/or prolonged fasting. Clinical presentations are similar to fatty acid oxidation defects; however, diagnosis of mHS deficiency is difficult because of poor biochemical markers. We report the case of a 12-month-old Japanese boy with mHS deficiency who presented with a coma, and hepatomegaly, but no hypoglycemia after a febrile episode and poor oral intake. Metabolic acidosis and severe fatty liver were observed. Serum acylcarnitine analysis revealed a slightly decreased free carnitine (C0) level and an increased acetylcarnitine (C2) level. Urinary organic acid analysis revealed hypoketotic dicarboxylic aciduria, and increased excretions of glutarate, and, retrospectively, 4-hydroxy-6-methyl-2-pyrone. Although the patient did not present with hypoglycemia, the severe fatty liver and elevated free fatty acids to total ketone bodies ratio strongly suggested an inborn error of ketogenesis. In the analysis of the HMGCS2 gene, compound heterozygous mutations of c.130_131ins C (L44PfsX29) and c.1156_1157insC (L386PfsX73) were identified, which led to the diagnosis of mHS deficiency. He had recovered without any complication by the therapy, including intravenous glucose infusion. Unlike the previously reported cases of mHS deficiency, our case did not present with hypoglycemia and the fatty liver lasted over several months. mHS deficiency should be taken into consideration when a patient has severe metabolic acidosis and fatty liver with no or subtle ketosis, even without hypoglycemia. SN - 2192-8304 UR - https://www.unboundmedicine.com/medline/citation/31392109/A_Japanese_case_of_mitochondrial_3_hydroxy_3_methylglutaryl_CoA_synthase_deficiency_who_presented_with_severe_metabolic_acidosis_and_fatty_liver_without_hypoglycemia_ L2 - https://dx.doi.org/10.1002/jmd2.12051 DB - PRIME DP - Unbound Medicine ER -
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