Juvenile spinal muscular atrophy: A new hexosaminidase deficiency phenotype

Abstract

A 24‐year‐old Ashkenazi Jewish man was evaluated for a nine‐year history of progressive leg weakness with fasciculations. Electromyography, nerve conduction velocities, muscle biopsy, and serum creatine kinase were consistent with anterior horn cell disease. On rectal biopsy, ganglion cells were filled with membranous cytoplasmic bodies and an unusual submucosal layer of periodic acid‐Schiff positive histiocytes filled with granules was seen. Hexosaminidase A in serum and leukocytes was severely decreased in the patient and partially decreased in the parents and a brother. A paternal relative had classic infantile Tay‐Sachs disease. Juvenile spinal muscular atrophy in this patient, closely resembling the Kugelberg‐Welander phenotype, resulted from an α‐locus hexosaminidase deficiency disorder, possibly a genetic compound of HEX_α² and a milder hexosaminidase α‐locus allele. Other cases of hexosaminidase deficiency have included anterior horn cell disease as part of a more complex disorder, but this is the first case, to our knowledge, of a hexosaminidase deficiency disorder presenting as spinal muscular atrophy.