Small fiber neuropathy in pediatric female heterozygotes of Fabry disease: a twin case report.

backgroundFabry disease, an X-linked lysosomal storage disorder, is associated with significant multisystem involvement, including small fiber neuropathy. While neuropathic pain is well-documented in females with Fabry disease, the objective confirmation of small fiber dysfunction in pediatric heterozygotes remains underreported. This study highlights the role of quantitative sensory testing (QST) in diagnosing small fiber neuropathy in young female patients. CASE REPORT: We present twin sisters, heterozygous for a pathogenic GLA variant (c.298 A > T), who exhibited symptoms of small fiber neuropathy, including acroparesthesia and gastrointestinal dysfunction. QST revealed altered thermoalgesic and vibratory thresholds in one twin and isolated vibratory hyposensitivity in the other, supporting the diagnosis of small fiber neuropathy. DISCUSSION: These cases highlight the diagnostic challenge of Fabry disease, as neuropathic symptoms may be overlooked or attributed to other conditions in pediatric patients. The findings emphasize the need for early identification of small fiber dysfunction in heterozygous females, who are increasingly recognized as being clinically affected. The complex alterations in sensory processing reinforce the importance of integrating QST as an objective assessment tool for small fiber function in Fabry disease.

conclusionsSmall fiber neuropathy is an early and clinically relevant manifestation of Fabry disease in pediatric heterozygotes. Early recognition and intervention, including enzyme replacement therapy (ERT), are essential to mitigating disease progression and improving clinical outcomes. These cases underscore the utility of QST in confirming small fiber neuropathy and highlight its potential role in the early diagnosis and monitoring of Fabry-related neuropathy in pediatric patients.