Perinatal-Onset Neuronopathic Gaucher Disease Is Refractory to High-Dose Ambroxol: A Case Report and Literature...

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.

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.

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.