Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase deficiency: From metabolism to clinical implications

Purpose Ketone bodies represent an important energy source and can contribute much to the energy supply of the brain. Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase deficiency (HMGCS2D) is an autosomal recessive disorder of ketogenesis caused by biallelic variants in HMGCS2. Only 59 pa...

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Detalles Bibliográficos
Autores: Grünert, Sarah C., Baumgartner, Matthias R., Bouchereau, Juliette, Burlina, Alberto, Clayton, Peter T., De las Heras Montero, Javier Adolfo, Dionisi-Vici, Carlo, Gemperle-Britschgi, Corinne, Haase, Claudia, Korman, Stanley H., Krämer, Johannes, Kühlwein, Eva, Maier, Esther M., Maiorana, Arianna, Schiff, Manuel, Schmid, Carl Ulrich, Tangeraas, Trine, Yamamoto, Raina, Zschocke, Johannes, Sass, Jörn Oliver
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/77069
Acceso en línea:http://hdl.handle.net/10810/77069
Access Level:acceso abierto
Palabra clave:HMGCS2
ketogenesis
ketone body metabolism
ketone body synthesis
mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency
Descripción
Sumario:Purpose Ketone bodies represent an important energy source and can contribute much to the energy supply of the brain. Mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase deficiency (HMGCS2D) is an autosomal recessive disorder of ketogenesis caused by biallelic variants in HMGCS2. Only 59 patients with this disorder have been reported so far. Methods We performed a comprehensive literature search to identify all published cases of HMGCS2D (n = 59). Additionally, the data of 16 patients with this disorder who are yet undescribed were collected. Clinical course, biochemical findings, and mutation data are highlighted and discussed. An overview on all HMGCS2 variants reported in patients is provided. Results Sixty-eight patients (91%) presented with an acute metabolic decompensation, mostly within the first year of life but beyond the neonatal period. Asymptomatic individuals were identified in several families. Six patients (8%) had died, mainly during the initial metabolic crisis. The neurologic long-term outcome of surviving patients was favorable with almost all patients (98%) showing normal development. Only 1 variant was identified to be common, (HMGCS2) NM_005518.4:c.634G>A p.(Gly212Arg), and found in 6 families. No genotype-phenotype correlation can be established. Conclusion This comprehensive data analysis provides an overview on all published patients reported with HMGCS2D, including a list of HMGCS2 variants identified in affected individuals.

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