Infantile Neuroaxonal Dystrophy; A Rare Or Underdiagnosed Disease?

Infantile Neuroaxonal Dystrophy; A Rare Or Underdiagnosed Disease? Objectives: Autosomal recessive cerebellar ataxia (ARCA) is a challenging diagnosis with heterogeneous manifestations. Low disease prevalence as well as insufficient physician knowledge, lead to incorrect diagnosis and inappropriate treatment. Precise diagnosis is mandatory in family planning, especially in a consanguineous background. Methods: During a period of 33 months (2019-2022) younger than 18 years old patients who suffered from early-onset ataxia were recruited to Ataxia Clinic, Children's Medical Center, Tehran University of medical sciences. Neurologic examinations, basic laboratory ataxia investigations, brain neuroimaging, and electrodiagnostic study were performed for all. Considering the clinical and Paraclinical scenario, a genetic study was performed. Results: 180 patients were registered while 168 cases were eligible for advanced evaluations. 19 patients (11%) were diagnosed with Infantile Neuroaxonal Dystrophy (INAD). PLA2G6 gene mutation and Cerebellar hemisphere/vermis hypoplasia were the most common genetic and neuroimaging findings, respectively. Cognitive deficit and seizure following motor development regression/delay are reported as the most frequent clinical findings. Conclusion: Regardless of the fact that INAD is not a common disease in everyday practice, it should be considered in an ataxic baby who presented with developmental delay/ regression, seizure, abnormal muscle tone, and abnormal cerebellar neuroimaging findings, especially in a consanguineous background. The correct diagnosis is critical for family planning. Furthermore, given that the PLA2G gene is the responsible gene in almost cases, a single-gene study lowers the cost that would be more noticeable in developing countries.
Keywords: Infantile Neuroaxonal Dystrophy, Ataxia, Cerebellar hypoplasia, PLA2G