charcot-marie-tooth-2d (CMT2D) Secondary to Novel GARS Mutation

Case Diagnosis: 34 year old female with Charcot-Marie-Tooth-2D (CMT2D) secondary to novel GARS mutation.

Case Description or Program Description: 34 year old female with CMT presents to clinic with progressive bilateral distal lower extremity weakness. Physical Exam showed Brooks 1, Vignos 3, bilateral peroneal muscle atrophy and steppage gait. Patient with abnormal electrodiagnostic results, warranting further genetic testing. Novel GARS mutation causing CMT confirmed with Invitae. Patient has 8 year-old son pending genetic testing.

Setting: Private Practice

Assessment/Results: GARS mutation has been reported across populations in Japan, South Korea, China, Europe, North America, and Asia. It is postulated as potential cause of CMT2 subtype D (CMT2D). Here we report a novel mutation in GARS causing CMT2D, in a Puerto Rican Family.

CMT2D is characterized as a hereditary sensory motor neuropathy secondary to axonal degeneration.

GARS is one of multiple genes that make up Aminoacyl-tRNA synthetase (ARS) gene family.

Patient with the GARS mutation experience a gradual progression of muscle weakness and atrophy that presents in adolescents. The distal upper limbs are affected first :Thenar and first interosseous muscles. As disease progresses involvement of the lower limbs in seen, including loss of vibratory sensation in late disease.

Age of symptom onset (adolescents) and sensory involvement in these patients rules out distal SMA V, suggesting CMT2D diagnosis.

Although the pathogenetic mechanism causing axonal neuropathy remains to be elucidated, studies suggest that mutation within the catalytic domain may cause axonal neuropathy. It is postulated that inheritance is autosomal dominant and mis-sense mutation of this region are pathologic. This domain houses essential enzymes needed in the first step of protein translation.

Discussion (relevance): This is the first reported case of novel GARS mutation of CMT2D in Puerto Rico.

Conclusions: Early diagnosis of variances of CMT are crucial, in order to provide early therapeutic and medical management.