Clinical Reasoning: Siblings with progressive weakness, hypotonia, nystagmus, and hearing loss

A Yemeni boy was born healthy at full term after an uncomplicated pregnancy and delivery. Head circumference (HC) at birth is unknown. At 3 months of age, he developed vomiting and failure to thrive. He was diagnosed with renal tubular acidosis (RTA). Targeted DNA analysis revealed ATP6V0A4 mutations associated with autosomal recessive distal RTA. Around 12 months of life, the patient developed horizontal nystagmus. At that time, his HC and height were approximately 10th percentile for age (45 cm and 74.9 cm, respectively). His development, the remainder of his neurologic examination, and brain MRI were normal. There were no birthmarks. He was lost to follow-up until 30 months of age, when he developed leg pain, progressive weakness of the lower, then upper extremities, dysarthria, decline in language skills, and sensorineural hearing loss following a mild viral illness. Examination at 30 months revealed normal muscle bulk, hypotonia, hyporeflexia, weakness (4/5 muscle strength throughout), and a wide-based gait. Bilateral wrist drop, finger contractures, decreased muscle bulk, and microcephaly (HC 2nd percentile, 46 cm) were noted at 53 months of age.