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Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 deficiency with severe hyperglycemia in a child: A rare case report

Year: 2025

Type: article

Abstract: Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (HMGCS2) deficiency is an exceptionally rare autosomal recessive metabolic disorder that impairs ketogenesis. It is typically characterized by hypoketotic hypoglycemia during periods of fasting or metabolic stress. Notably, severe hyperglycemia as an initial presenting symptom has not been previously reported. We report the case of a 6-month-old girl who suddenly developed coma after 1 day of fasting due to repeated vomiting during pneumonia. At presentation, she had hyperglycemia (25.8 mmol/L), ketonuria (1+), glucosuria (3+), metabolic acidosis (pH 6.90), elevated serum alanine transaminase and aspartate aminotransferase levels, increased blood ammonia levels, and liver enlargement on ultrasound. However, fasting insulin, glucagon, and glycated hemoglobin levels were all within the normal range. Whole-exome sequencing identified compound heterozygous mutations in the HMGCS2 gene-c.1175C>T (p.S392L) inherited from the father and c.719A>T (p.A240V) inherited from the mother-thereby confirming the diagnosis of HMGCS2 deficiency. This case highlights severe hyperglycemia as an atypical clinical feature of HMGCS2 deficiency. Increased awareness of such rare manifestations may assist in improving early diagnosis and treatment of this condition.

Source: Journal of International Medical Research

DOI: 10.1177/03000605251375537

Authors: Chang Dong, Tiantian Lu, Yazhou Jiang, Zihao Yan, Suyue Zhu

Institution: Xuzhou Medical College

Language: English

Topic: Metabolism and Genetic Disorders

Subfield: Clinical Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,155