Familial Adult-Onset Proximal Spinal Muscular Atrophy

DURING the investigations of a family with type II hyperlipoproteinemia (familial hyperbetalipoproteinemia), 1 it was noted that the four older affected male members also had a slowly progressive neuromuscular disorder which had developed in early adulthood. The major clinical features included fasciculations of face, tongue, trunk, and limb muscles, excessive cramping of involved muscles with moderate exertion, muscle weakness predominantly proximal in the arms and legs with associated atrophy and reduction of deep tendon reflexes, and mild elevation in cerebrospinal fluid (CSF) protein content. Electromyographs, nerve conduction studies, and muscle biopsy in each case confirmed the neuropathic basis of the disease. The entire accessible family was subsequently evaluated for both the serum lipoprotein abnormality and the neurological disorder. Materials and Methods The propositus, a 47-year-old man, and his four siblings, a 50-year-old man, a 46-year-old man, a 43-year-old woman, and a 37-year-old man, were admitted to the Clinical Center