Patient 1 is a 43-year-old woman who developed head drop in infancy, followed by gross motor incoordination in early childhood, and difficulty climbing stairs and easy fatigability in early adulthood. Her exam demonstrated proximal lower extremity weakness, calf hypertrophy, and waddling gait. Diagnostic evaluation revealed hyperCKemia, electrodecrement on repetitive nerve stimulation, myopathic features on muscle biopsy, and abnormal muscle MRI. Genetic testing demonstrated a two variants in GMPPB: c.79G>C (p.Asp27His), classified as pathogenic and c.1043_1044insAGA (p.Glu348dup), classified as uncertain significance. Pyridostigmine has improved her muscle fatigability.

Patient 2 is a 33-year-old man who required special education schooling. His early motor development was reported to be normal. At age 24, he developed difficulty rising from chairs and climbing stairs, noting fluctuating arm and leg weakness. On exam, he has bilateral scapular winging, calf hypertrophy, waddling gait, and proximal-predominant weakness. Diagnostic evaluation revealed hyperCKemia, electrodecrement on repetitive nerve stimulation, and irritable myopathy on needle EMG. Genetic testing demonstrated two variants in GMPPB: c.988G>A (p.Val330Ile), classified as pathogenic, and c.62C>A (p.Thr21Asn), classified as uncertain significance. Pyridostigmine and 3,4-diaminopyridine have improved his muscle fatigability.