Lysosomal Acid Lipase (LAL) Deficiency Registry

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.

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.