HMGCR is an enzyme 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-in mouse, confirmed the deleterious nature of this mutation.
This case, unique in terms of the early onset and severity of the clinical picture, joins the twenty or so other cases already published.
