Neurodegeneration with Brain Iron Accumulation Mimicry in a Pediatric-Onset Spinocerebellar Ataxia Type 2: A Case Report

Abstract

Introduction: Spinocerebellar Ataxia Type 2 (SCA2) is an autosomal dominant, multisystem neurodegenerative disease caused by a pathogenic CAG trinucleotide repeat expansion in the ATXN2 gene. Its pediatric onset is exceptionally rare, characterized by aggressive progression and a predominantly dystonic-spastic phenotype that relegates ataxia to a secondary feature. Premature degeneration of the globus pallidus has been documented in early-onset variants, conditioning neuroimaging abnormalities that mimic Neurodegeneration with Brain Iron Accumulation (NBIA) syndromes and lead to initial misdiagnoses.

Objective: To describe the challenge of molecular differential diagnosis and the comprehensive medical rehabilitation approach in a pediatric patient with a mixed phenotype secondary to SCA2 mimicking an NBIA syndrome.

Case Presentation: A 10-year-old male patient from Puebla, with a family history of an older brother with a similar motor disorder. Product of a second pregnancy, delivered via cesarean section at 38 weeks of gestation due to oligohidramnios (birth weight: 3,850 g); he presented with a chronological delay in developmental milestones and a history of speech therapy for dyslalia. The current illness began at age 8 with progressive postural abnormalities in the left lower limb (claw toes), pain, and functional limitation during ambulation. Subsequently, the ipsilateral upper limb became involved with focal dystonia in the wrist and fingers, alongside tension-type headache and emotional lability. Initial electromyography was normal. However, brain magnetic resonance imaging (MRI) revealed focal hypointensity in the right globus pallidus compatible with hemosiderin deposits, raising suspicion for NBIA. Given the atypical onset, clinical exome sequencing was requested, which reported a pathogenic heterozygous expansion variant in ATXN2 with 39 repeats (estimated range 38-39), confirming SCA2. During the March 2026 evaluation, he exhibited decreased strength in the left hemicorpus (4/5), Ashworth grade II spastic hypertonia, an ipsilateral Babinski sign, focal dystonia with claw hand and foot, and a spastic-dystonic hemiparetic gait.

Discussion: Pediatric-onset SCA2 challenges clinical diagnosis by replacing classic ataxia with an accelerated dystonic-spastic phenotype. The erroneous suspicion of NBIA stemmed from the palidal hypointensity; nevertheless, literature demonstrates that pallidoluysian involvement is a hallmark feature in early variants of SCA2, explaining both the molecular neuroimaging findings and the dystonia (Seidel et al.). The 39 repeats in ATXN2 corroborate full penetrance correlated with the pediatric phenotype aggressiveness. From a rehabilitation perspective, managing the mixed tone required botulinum toxin type A infiltration into the target muscles of the left lower limb, a resting hand splint, and intensive physical therapy (neurofacilitation and stretching), thereby modulating spasticity and optimizing gait kinematics.

Conclusions: Pediatric SCA2 can masquerade as NBIA due to early palidal involvement. Faced with complex motor phenotypes during childhood, exome-based molecular diagnosis is mandatory. Diagnostic certainty guides medical rehabilitation therapeutic decisions, optimizing functionality and limiting restriction in participation.