Rapid disease progression after enzyme replacement therapy interruption in a patient with cholesteryl ester storage disorder

ABSTRACT

Lysosomal acid lipase deficiency (LALD) has two clinical phenotypes an infantile-onset form - Wolman disease (WD) presented by severe malabsorption, cholestasis, malnutrition, hepatosplenomegaly and early death, and a later-onset form - cholesteryl ester storage disorder (CESD) with hepatosplenomegaly, dyslipidemia, malabsorption and variable disease severity manifestation. Enzyme replacement therapy (ERT) with sebelipase alfa was approved by the Brazilian Health Regulatory Agency (ANVISA) in 2017. We report the deleterious effect of ERT interruption in a CESD patient. Male, 16y, diagnosed at 7y, positive familiar history with mother, grandfather and three siblings affected. He was enrolled in the phase 3 clinical trial from age 9-12y under the 3 mg/Kg dose regimen. Then he enrolled in the post-study donation program under the same dose. Due to personal, importation and supply issues, and the COVID-19 pandemic restrictions, he had a progressive decrease in treatment adherence rate 68% at 12y, 27% at 13y, 30% at 14y and after that he had an interruption of 1 entire year. At 15y he presented with generalized edema, severe fatigue, tachycardia, was hospitalized, diagnosed low serum iron, albumin and protein, acute anemia (hemoglobin 6.2 g/dL - normal range of 12,5-13,5), and received blood transfusion. In the next year, still without ERT, he was hospitalized again due to generalized edema, acute anemia (Hemoglobin = 6.9 g/dL) and worsening of hypoalbuminemia and iron deficiency, and received blood transfusion. Although our patient has the CESD phenotype, the ERT interruptions did not worsen the liver involvement nor the dyslipidemia, but caused a severe malabsorption which is classically described in WD phenotype. In conclusion, this case serves as an alert that when ERT is interrupted, there is a rapid clinical deterioration. Acknowledgements to IGEIM, and Drs Felippe Raphael e Oliveira Previdi and Ana Eduarda Saraiva Pereira Campos for clinical assistance of the patient.