Action myoclonus-renal failure syndrome

Action myoclonus-renal failure syndrome (AMRF), also known as progressive myoclonus epilepsy with renal failure, is an extremely rare autosomal recessive disorder caused by mutations in the SCARB2 gene (also known as LIMP2), which encodes a lysosomal membrane protein important for the proper trafficking of the enzyme glucocerebrosidase. The disease typically manifests in adolescence or young adulthood and is characterized by progressive action myoclonus (involuntary jerking movements triggered by voluntary actions), seizures, tremor, and progressive renal failure due to focal segmental glomerulosclerosis or other forms of glomerular disease. The neurological and renal manifestations may not always appear simultaneously; some patients present first with proteinuria and renal dysfunction, while others initially develop neurological symptoms. The nervous system and kidneys are the primary organ systems affected. Neurological features include action myoclonus that can be severely disabling, generalized tonic-clonic seizures, cerebellar ataxia, and progressive cognitive decline. Renal involvement typically presents as proteinuria progressing to nephrotic syndrome and eventually end-stage renal disease requiring dialysis or transplantation. Some patients may also develop sensorineural hearing loss. The combination of progressive myoclonus epilepsy with renal failure is highly suggestive of this diagnosis. There is currently no curative treatment for AMRF syndrome. Management is supportive and symptomatic. Antiepileptic medications such as levalbuterol, clonazepam, valproate, and levetiracetam may be used to manage myoclonus and seizures, though response is often incomplete and myoclonus tends to be refractory to treatment. Renal replacement therapy, including dialysis and kidney transplantation, is used to manage end-stage renal disease. The prognosis is generally poor, with progressive neurological deterioration over time. Genetic counseling is recommended for affected families.

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