Perinatal-onset neuronopathic Gaucher disease is refractory to high-dose ambroxol: A case report and literature review

Introduction: High-dose ambroxol is an effective pharmacological chaperone therapy for the systemic and neurological symptoms of Gaucher disease (GD). However, no clinical evidence of perinatal-onset GD has been documented. Case presentation: The patient had perinatal-onset neuronopathic GD (PnGD) and received high-dose ambroxol, beginning at 10 days of life after a newborn screening report. There was a transient hematological response after combined ambroxol and enzyme replacement therapy; however, laryngospasm, epileptic seizures, liver dysfunction, and heart failure progressed. The patient died 95 days after birth. Genetic testing revealed a homozygous L483R variant in GBA1. A literature review of 56 patients with nGD confirmed poor survival outcomes for patients with PnGD. Conclusion: Ambroxol therapy may be insufficient to improve the prognosis of patients with PnGD, underscoring the limitations of early intervention in newborn-screened patients with GD. Therefore, pre-emptive therapeutic strategies are required to rescue and cure neonates with PnGD.