HMGCR-related muscular dystrophy: a case of severe neonatal-onset form

Le résumé fourni par la source

We report a case of HMGCR-related limb-girdle muscular dystrophy (LGMD) with neonatal onset and early lethality. The patient, homozygous for the p.Arg641Cys variant in HMGCR, presented with profound hypotonia, respiratory failure by 5 months, and markedly elevated creatine kinase (CK). This case stands out among the 17 previously reported patients for its extremely early onset and rapid clinical deterioration. Functional studies confirmed the pathogenicity of the variant: in vitro assays showed severely impaired HMGCR enzymatic activity, and in vivo modeling using homozygous knock-in mice resulted in embryonic lethality, underscoring its deleterious effect on essential metabolic processes. The patient's early death highlights the urgent need for targeted therapies and early diagnosis. This case expands the clinical and molecular spectrum of HMGCR-related LGMD and supports refining phenotype classification based on genotype-phenotype correlations and age of onset to improve diagnostic precision.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.