lysosomal acid lipase (lal) deficiency registry

Conditions: Lysosomal Acid Lipase Deficiency; Cholesterol Ester Storage Disease; Wolman Disease; Acid Cholesteryl Ester Hydrolase Deficiency, Type 2; Acid Lipase Deficiency; LIPA Deficiency; LAL-Deficiency

Summary: this is an observational, multi-center, international disease registry designed to collect longitudinal data and create a knowledge base that will be utilized to improve the care and treatment of patients with lal deficiency. participation in the registry by both physicians and patients is voluntary.

lysosomal acid lipase (lal) deficiency is a rare autosomal recessive lysosomal storage disorder (lsd) that is caused by a marked decrease of lysosomal acid lipase (lal), the enzyme that breaks down cholesteryl esters and triglycerides in the lysosomes. lysosomal acid lipase deficiency presenting in infants (historically called wolman disease) is a medical emergency with rapid disease progression over a period of weeks that is typically fatal within the first 6 months of life. more commonly, lal deficiency presents in children and adults and this presentation has been historically called cholesteryl ester storage disease (cesd). in general, data on the prevalence of lal deficiency are limited, and the overall prevalence of the disease in the population is unclear. for all presentations, lal deficiency is associated with significant morbidity and mortality. deficient lal enzyme activity results in the lysosomal accumulation of cholesteryl esters and triglycerides. in the liver, this accumulation leads to hepatomegaly, increased hepatic fat content, transaminase elevation signaling chronic liver injury, and progression to fibrosis, cirrhosis, and complications of end stage liver disease. in the spleen, lal deficiency results in splenomegaly, anemia, and thrombocytopenia. lipid accumulation in the intestinal wall leads to malabsorption and growth failure. dyslipidemia is common with elevated low density lipoprotein (ldl) and triglycerides and low high density lipoprotein (hdl), associated with increased liver fat content and transaminase elevations. in addition to liver disease, patients with lal deficiency experience increased risk for cardiovascular disease and accelerated atherosclerosis. the lal deficiency registry is a global registry, established to help improve care for patients through improved understanding of the disease and long-term effectiveness of therapeutic interventions including sebelipase alfa. as with other registries, which are becoming increasingly valuable for collecting information in large, heterogeneous, 'real world' populations, the lal deficiency registry aims to provide evidence to help support patient care and inform clinical practice. this registry is also being conducted, in part, to fulfill post-marketing commitments and requirements agreed to by the sponsor as a condition for sebelipase alfa approval in the eu and the usa.

Eligibility criteria:
patients must have a confirmed diagnosis of lal deficiency. an informed consent and authorization must be obtained prior to patient enrollment where required under applicable laws and regulations, or a waiver must be obtained by the institutional review board/independent ethics committee. patients cannot be currently participating in an alexion-sponsored clinical trial. patients who have concluded participation in an alexion-sponsored sebelipase alfa clinical trial are eligible to enroll in this registry, and enrollment in the registry will not exclude a patient from enrolling in a future clinical trial.