Neurodevelopmental regression Due to PLA2G6-associated neurodegeneration despite normal brain MRI: a case report

Infantile neuroaxonal dystrophy is a rare autosomal recessive neurodegenerative disorder within the spectrum of PLA2G6-associated neurodegeneration. It is typically characterized by early psychomotor regression, progressive motor impairment, bulbar dysfunction, and characteristic neuroimaging abnormalities, including cerebellar atrophy and, in some cases, brain iron accumulation.

We report the case of a 4-year-11-month-old girl with progressive neurodevelopmental regression beginning at approximately 18 months of age. The patient presented with loss of previously acquired motor abilities, absence of verbal language, marked hypotonia, preserved deep tendon reflexes, and progressive feeding difficulties. Laboratory evaluation was largely unremarkable, except for persistent isolated elevation of aspartate aminotransferase (AST). Brain MRI showed no overt structural or signal abnormalities despite advanced neurological impairment. Electroencephalography (EEG) did not reveal epileptiform activity. Given the progressive course and suspicion of an underlying neurodegenerative disorder, whole-exome sequencing was performed and identified a homozygous PLA2G6 variant, supporting the diagnosis of PLA2G6-associated neurodegeneration. During follow-up, the patient developed dysphagia and grade II gastroesophageal reflux, requiring gastrostomy placement and Nissen fundoplication.

This case highlights the importance of early molecular diagnosis in pediatric regression syndromes and emphasizes that normal neuroimaging does not exclude PLA2G6-associated neurodegeneration, particularly in atypical presentations. Early recognition enables timely multidisciplinary management, prognostic assessment, and appropriate genetic counseling for the family.