Childhood onset homozygous recessive GDAP1 (p.Pro231Leu) mutation in a 9-year-old puerto rican pediatric female with axonal Charcot-Marie-Tooth disease: A case report

Article type: Research Article

Authors: Ortiz-Santiago, Ana | Ramos, Edwardo^{; *}

Affiliations: Physical Medicine and Rehabilitation, University of Puerto Rico School of Medicine, San Juan, Puerto Rico

Correspondence: [*] Corresponding author: Edwardo Ramos, MD, Department of Physical Medicine and Rehabilitation, PO Box 365067, San Juan, 00936-5067, Puerto Rico. Tel.: +1 7874063206; E-mail: [email protected].

Abstract: Charcot-Marie-Tooth disease (CMT) is a progressive hereditary neuromuscular neuropathy with pathology in the myelin sheath or the axon. CMT caused by mutations in the Ganglioside-induced differentiation associated protein 1 (GDAP1) gene has been described by a spectrum of phenotypic presentations. GDAP1 is a mitochondrial protein responsible for protecting neuronal bodies from oxidative stress. It is associated with axonal and demyelinating pathophysiology with recessive and dominant modes of inheritance.We describe a case of a 9-year-old Puerto Rican female with clinical and electrodiagnostic results compatible with an axonal sensory-motor neuropathy where a genetic test describes a homozygous GDAP1 missense mutation at the c.692C>T (p.Pro231Leu), previously undetected in a pediatric Latino patient. Mutations in GDAP1 have been previously described in Tunisian, Old Order Amish, European and Japanese families with varying modes of inheritance. To our knowledge, this homozygous variant presentation of the GDAP1 gene is the first to be described in a pediatric Puerto Rican patient without a family history of hereditary sensory motor neuropathy.

Keywords: GDAP1, Charcot-Marie-Tooth disease, axonal neuropathy, pes-cavus

DOI: 10.3233/PRM-200695

Journal: Journal of Pediatric Rehabilitation Medicine, vol. 14, no. 3, pp. 533-537, 2021