Abstract
BackgroundWolman disease (WD), the rapidly progressive phenotype of lysosomal acid lipase (LAL) deficiency, presents in neonates with failure to thrive and hepatosplenomegaly, and leads to multi-organ failure and death before 12 months of age. In clinical trials, enzyme replacement therapy (ERT) with sebelipase alfa led to improved survival, growth and biological parameters in WD patients followed up to 5 years. Long-term follow-up and health-related quality of life (HRQoL) evaluation are lacking.ResultsWe performed a nationwide, retrospective study of sebelipase alfa in WD patients. Five patients with abolished LAL activity and bi-allelic LIPA mutations were included with a median follow-up of 7 years (1–10). ERT was initiated at a median age of 1 month (0–4). Infusion tolerance was excellent on the long-term with only one patient requiring systematic pre-medication. Cholestyramine, fat-soluble vitamin supplements and a specific diet (high in medium-chain triglycerides and low in long-chain fatty acids) were prescribed. Liver function tests, plasma lipid profiles, fat-soluble vitamin levels and growth parameters improved. Three patients transiently exhibited a neuromyopathic phenotype (footdrop gait, waddling walk or muscle fatigue) but electromyography and muscle strength testing were normal. At last follow-up, all patients were alive with normal growth parameters and a satisfactory HRQoL, no patient had special education needs, and one patient required parenteral nutrition since an acute gastroenteritis.ConclusionsEarly ERT initiation allowed 100% survival with positive outcomes. Very long-term follow-up and hematopoietic stem cell transplantation while on ERT should be evaluated to strengthen the benefits of sebelipase alfa.
Highlights
Wolman disease (WD), the rapidly progressive phenotype of lysosomal acid lipase (LAL) deficiency, pre‐ sents in neonates with failure to thrive and hepatosplenomegaly, and leads to multi-organ failure and death before 12 months of age
LALD phenotypes form a continuous spectrum between Wolman disease (WD) [4, 5] and cholesterol ester storage disease (CESD)
We report here the longest follow-up to date, of 5 WD patients treated with sebelipase alfa for a median duration of 7 years (1–10)
Summary
Wolman disease (WD), the rapidly progressive phenotype of lysosomal acid lipase (LAL) deficiency, pre‐ sents in neonates with failure to thrive and hepatosplenomegaly, and leads to multi-organ failure and death before 12 months of age. Lysosomal acid lipase (LAL, EC 3.1.1.13) deficiency (LALD, MIM 278000) is an ultrarare lysosomal storage disease (LSD) associated with bi-allelic LIPA pathogenic variants causing strongly decreased LAL activity [1]. LALD phenotypes form a continuous spectrum between Wolman disease (WD) [4, 5] and cholesterol ester storage disease (CESD). WD patients present in the first months of life with failure to thrive, malabsorption, hepatosplenomegaly, liver failure and bilateral adrenal calcifications [7]. CESD has a higher prevalence of 1 per 160,000 [9], and presents during childhood or adulthood with hepatomegaly, elevated liver enzymes and dyslipidemia [10]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.