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Severe clinical manifestation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency associated with two novel mutations: a case report.
BMC Pediatr. 2019 10 09; 19(1):344.BPed

Abstract

BACKGROUND

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) deficiency is an autosomal recessive inborn error of metabolism, which will give rise to failure of ketogenesis in liver during illness or fasting. It is a very rare disease with only a few patients reported worldwide, most of which had a good prognosis after proper therapies.

CASE PRESENTATION

We report a 9-month-old boy with mHS deficiency presenting with unusually severe and persistent acidosis after diarrhea and reduced oral food intake. The metabolic acidosis persisted even after supplementation with sugar and alkaline solution. Blood purification and assisted respiration alleviated symptoms, but a second onset induced by respiratory infection several days later led to multiple organ failure and death. Urine organic acid analysis during the acute episode revealed a complex pattern of ketogenic dicarboxylic and 3-hydroxydicarboxylic aciduria with prominent elevation of glutaric acid and adipic acid, which seem to be specific to mHS deficiency. Plasma acylcarnitine analysis revealed elevated 3-hydroxybutyrylcarnitine and acetylcarnitine. This is the first report of elevated 3-hydroxybutyrylcarnitine in mHS deficiency. Whole exome sequencing revealed a novel compound heterozygous mutation in HMGCS2 (c.100C > T and c.1465delA).

CONCLUSION

This severe case suggests the need for patients with mHS deficiency to avoid recurrent illness because it can induce severe metabolic crisis, possibly leading to death. Such patients may also require special treatment, such as blood purification. Urine organic acid profile during the acute episode may give a hint to the disease.

Authors+Show Affiliations

Center for Clinical Molecular Medicine, Chongqing, 400014, People's Republic of China. Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing, 400014, People's Republic of China. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, People's Republic of China. China International Science and Technology Cooperation base of Child Development and critical Disorders, Chongqing, 400014, People's Republic of China. Chongqing key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.Center for Clinical Molecular Medicine, Chongqing, 400014, People's Republic of China. Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing, 400014, People's Republic of China. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, People's Republic of China. China International Science and Technology Cooperation base of Child Development and critical Disorders, Chongqing, 400014, People's Republic of China. Chongqing key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.Center for Clinical Molecular Medicine, Chongqing, 400014, People's Republic of China. Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing, 400014, People's Republic of China. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, People's Republic of China. China International Science and Technology Cooperation base of Child Development and critical Disorders, Chongqing, 400014, People's Republic of China. Chongqing key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.Center for Clinical Molecular Medicine, Chongqing, 400014, People's Republic of China. Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing, 400014, People's Republic of China. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, People's Republic of China. China International Science and Technology Cooperation base of Child Development and critical Disorders, Chongqing, 400014, People's Republic of China. Chongqing key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.Center for Clinical Molecular Medicine, Chongqing, 400014, People's Republic of China. Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing, 400014, People's Republic of China. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, People's Republic of China. China International Science and Technology Cooperation base of Child Development and critical Disorders, Chongqing, 400014, People's Republic of China. Chongqing key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.Center for Clinical Molecular Medicine, Chongqing, 400014, People's Republic of China.Center for Clinical Molecular Medicine, Chongqing, 400014, People's Republic of China. Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing, 400014, People's Republic of China. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, People's Republic of China. China International Science and Technology Cooperation base of Child Development and critical Disorders, Chongqing, 400014, People's Republic of China. Chongqing key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.Center for Clinical Molecular Medicine, Chongqing, 400014, People's Republic of China. Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing, 400014, People's Republic of China. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, People's Republic of China. China International Science and Technology Cooperation base of Child Development and critical Disorders, Chongqing, 400014, People's Republic of China. Chongqing key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing, 400014, People's Republic of China. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, People's Republic of China. China International Science and Technology Cooperation base of Child Development and critical Disorders, Chongqing, 400014, People's Republic of China. Chongqing key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China. Department of Endocrinology, Chongqing, 400014, People's Republic of China.Center for Clinical Molecular Medicine, Chongqing, 400014, People's Republic of China. Zoulin74@126.com. Ministry of Education Key Laboratory of Child Development and Disorder, Chongqing, 400014, People's Republic of China. Zoulin74@126.com. National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, People's Republic of China. Zoulin74@126.com. China International Science and Technology Cooperation base of Child Development and critical Disorders, Chongqing, 400014, People's Republic of China. Zoulin74@126.com. Chongqing key Laboratory of Pediatrics, Chongqing, 400014, People's Republic of China. Zoulin74@126.com. Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China. Zoulin74@126.com.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

31597564

Citation

Liu, Hao, et al. "Severe Clinical Manifestation of Mitochondrial 3-hydroxy-3-methylglutaryl-CoA Synthase Deficiency Associated With Two Novel Mutations: a Case Report." BMC Pediatrics, vol. 19, no. 1, 2019, p. 344.
Liu H, Miao JK, Yu CW, et al. Severe clinical manifestation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency associated with two novel mutations: a case report. BMC Pediatr. 2019;19(1):344.
Liu, H., Miao, J. K., Yu, C. W., Wan, K. X., Zhang, J., Yuan, Z. J., Yang, J., Wang, D. J., Zeng, Y., & Zou, L. (2019). Severe clinical manifestation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency associated with two novel mutations: a case report. BMC Pediatrics, 19(1), 344. https://doi.org/10.1186/s12887-019-1747-5
Liu H, et al. Severe Clinical Manifestation of Mitochondrial 3-hydroxy-3-methylglutaryl-CoA Synthase Deficiency Associated With Two Novel Mutations: a Case Report. BMC Pediatr. 2019 10 9;19(1):344. PubMed PMID: 31597564.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Severe clinical manifestation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency associated with two novel mutations: a case report. AU - Liu,Hao, AU - Miao,Jing-Kun, AU - Yu,Chao-Wen, AU - Wan,Ke-Xing, AU - Zhang,Juan, AU - Yuan,Zhao-Jian, AU - Yang,Jing, AU - Wang,Dong-Juan, AU - Zeng,Yan, AU - Zou,Lin, Y1 - 2019/10/09/ PY - 2019/05/24/received PY - 2019/09/24/accepted PY - 2019/10/11/entrez PY - 2019/10/11/pubmed PY - 2020/11/11/medline KW - Hypoglycemia KW - Inherited metabolic disorders KW - Ketogenesis KW - Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase SP - 344 EP - 344 JF - BMC pediatrics JO - BMC Pediatr VL - 19 IS - 1 N2 - BACKGROUND: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) deficiency is an autosomal recessive inborn error of metabolism, which will give rise to failure of ketogenesis in liver during illness or fasting. It is a very rare disease with only a few patients reported worldwide, most of which had a good prognosis after proper therapies. CASE PRESENTATION: We report a 9-month-old boy with mHS deficiency presenting with unusually severe and persistent acidosis after diarrhea and reduced oral food intake. The metabolic acidosis persisted even after supplementation with sugar and alkaline solution. Blood purification and assisted respiration alleviated symptoms, but a second onset induced by respiratory infection several days later led to multiple organ failure and death. Urine organic acid analysis during the acute episode revealed a complex pattern of ketogenic dicarboxylic and 3-hydroxydicarboxylic aciduria with prominent elevation of glutaric acid and adipic acid, which seem to be specific to mHS deficiency. Plasma acylcarnitine analysis revealed elevated 3-hydroxybutyrylcarnitine and acetylcarnitine. This is the first report of elevated 3-hydroxybutyrylcarnitine in mHS deficiency. Whole exome sequencing revealed a novel compound heterozygous mutation in HMGCS2 (c.100C > T and c.1465delA). CONCLUSION: This severe case suggests the need for patients with mHS deficiency to avoid recurrent illness because it can induce severe metabolic crisis, possibly leading to death. Such patients may also require special treatment, such as blood purification. Urine organic acid profile during the acute episode may give a hint to the disease. SN - 1471-2431 UR - https://www.unboundmedicine.com/medline/citation/31597564/Severe_clinical_manifestation_of_mitochondrial_3_hydroxy_3_methylglutaryl_CoA_synthase_deficiency_associated_with_two_novel_mutations:_a_case_report_ L2 - https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-019-1747-5 DB - PRIME DP - Unbound Medicine ER -