BACKGROUND: Fabry disease is a multisystem disease, with the most serious clinical impact observed in the heart, kidneys and central nervous system (CNS). Neuropathic pain is a key symptom in children with Fabry disease since it is often the earliest manifestation, and it has a considerable impact on overall quality of life.

CASE SERIES: Here we report the cases of two young boys presenting with pain as the only clinical manifestation of Fabry disease, both receiving enzyme replacement therapy. The first patient experienced a partial symptom improvement and is currently under clinical monitoring to detect whether adjunctive symptomatic treatment is needed. The second one showed a progressive worsening of pain over time despite treatment escalation and developed drug dependence and associated significant psychological burden.

CONCLUSIONS: These two cases underline the need for accurate and objective pain measurement tools to define the correct time to start supportive treatments and to monitor treatment efficacy. Moreover, the second case remarks on the difficulties in pain management due to the lack of specific guidelines, the risk of overtreatment, and the importance of a multidisciplinary follow-up, including a thorough psychological evaluation in these patients. National and international collaborations are needed to standardize pain measurement modalities and improve symptomatic treatment management, ideally through prospective clinical studies.