Abstract
Objective: To report a rare homozygous mutation in GDAP1 (Ganglioside-induced differentiation-associated protein 1) as a cause of autosomal recessive Charcot-Marie-Tooth disease (CMT).
Background: Mutations in GDAP1 represent up to 1% of all forms of CMT and 2–4% of autosomal recessive CMT (AR CMT). These mutations are associated with 4 CMT subtypes: CMT4A, CMT2H, CMTRIA and CMT2K. The most common phenotype is characterized by early onset of a motor predominant neuropathy with vocal cord paralysis and loss of ambulation by the second decade. The c.692C>T variant has only been reported in 3 siblings from a single Amish family with AR CMT.
Design/Methods: Case report and review of the literature.
Results: A 33 year-old man from Puerto Rico presented with weakness. He had normal motor milestones during early childhood but started falling at age 6. Symptoms progressed slowly over time. He developed hand weakness and bilateral foot drop a few years before his presentation. There was no family history of similar symptoms. Examination demonstrated distal weakness and atrophy involving the arms and legs, areflexia, and distal sensory loss. There was no extraocular, facial, bulbar or respiratory muscle weakness, and no upper motor neuron signs. An electrodiagnostic study demonstrated a non-length dependent, sensorimotor, primarily axonal neuropathy. Workup for acquired causes of neuropathy led to a new diagnosis of type 2 diabetes (Hemoglobin A1C 10.6%, normal <5.7%). Given the high clinical suspicion for a hereditary neuropathy, the patient underwent genetic testing, which identified a homozygous mutation c.692C>T (p.Pro231Leu) in GDAP1.
Conclusions: The c.692C>T mutation in GDAP1 is associated with AR CMT. Our case suggests that the mutation is not restricted to the Amish population. The phenotype seems to be milder compared to other forms of GDAP1-related AR CMT. In our case, diabetes likely contributed to the neuropathy but did not fully explain the phenotype.
Disclosure: Dr. Vivar has nothing to disclose. Dr. Avila has nothing to disclose.
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