An unprecedented paediatric case of myopathy linked to the HMGCR gene

HMGCR is an enzymeProtéine capable d’activer une réaction biochimique précise. involved in the metabolism of cholesterol and other metabolites. Until now, it was best known in connection with autoimmune necrotising myopathy (AINM) with anti-HMGCR autoantibodies, following statin use:

• American and Japanese clinicians report an unprecedented case of hereditary myopathy linked to the gene encoding this enzyme but occurring at a very early age, unlike other cases reported in the literature;
• in this case, it was an infant who presented with severe hypotonia and rapidly fatal respiratory failure;
• genetic testing identified a homozygous pathological variant of the HMGCR gene (p.Arg641Cys);
• functional studies, including in a knock-inTechnique permettant d’invalider un gène et de le remplacer par un autre gène. mouse, confirmed the deleterious nature of this mutationModification soudaine et transmissible du matériel génétique. Elle peut être spontanée ou induite par des agents dits » mutagènes » (radiations, produits toxiques,…)..

This case, unique in terms of the early onset and severity of the clinical picture, joins the twenty or so other cases already published.

HMGCR-related muscular dystrophy: a case of severe neonatal-onset form. Upadia J, Li Y, Osaki Y et al. Neuromuscul Disord. 2025 Nov 26;58:106299.