Lysosomal Acid Lipase deficiency (LAL D) is lysosomal metabolic genetic disease caused by mutation in LIPA gene which encodes for the LAL enzyme. It characterised by multiorganic damage, mostly liver and spleen connected with lipid accumulation. In children it could progress very fast resulting liver cirrhosis and possibly death.
We have observed case of LAL D child for 16 years (from 1,6 y.o. till now 17 y.o.) with fast progression of the disease to liver cirrhosis. Girl was born in 1998 in healthy family with consanguineous parents. At age of 10 month hepatomegaly was revealed, examinations were not performed. In 1,2 year was admitted to the hospital for the first time hepatosplenomegaly (liver+6 cm, spleen+5 cm), anaemia, cytolysis (transaminase increase ALT up to 4N, AST up to 2N), hypercholesterolemia (9,7 mmol/L), triglyceridemia (2,3 mmol/L) were found. Diseases such as thalassemia, viral hepatitis, prenatal infections, metabolic disorders were excluded. Lysosomal acid lipase (LAL) activity was low due to which cholesterol ester storage disease was diagnosed. At age of 3 year patient had bleeding from the extracted tooth site, was sutured. At the same clinic terminal erosive esophagitis was diagnosed. Liver was+6 cm, spleen+10 cm. ALT up to 9N, AST up to 8N, hypercholesterolemia (7,98 mmol/L), LDL-C 7,64 mmol/L. Repeated analysis of LAL activity confirmed significant deficiency. In 2004 (6 y.o.) patient was consulted in Germany (Freiburg) where LAL activity in leucocytes was estimated and confirmed cholesterol ester storage disease. No special treatment was prescribed. In 2008 (10 y.o.) on planned hospitalisation progression of the disease was observed: liver+3 cm, spleen+12 cm, thrombocytopenia, on US signs of significant periportal cirrhosis was revealed. Fibroelastographia showed liver fibrosis F4 (METAVIR). In 2 years (2010) repeated Fibroelastographia showed significant fibrosis/cirrhosis. CT-scan confirmed picture of cirrhosis and signs of portal hypertension. Nasal bleeding episodes occurred. Constant progression of the disease confirmed in 2012 (age 14 y.o.) on planned hospitalisation: thrombocytopenia, leucopenia, hepatosplenomegaly, liver cirrhosis, portal hypertension, liver-cell insufficiency (Child-Pugh scale was 11 out of 15). Transplantologists recommended orthotopic liver transplantation, which till 2015 was not performed. The possibility of clinical trial participation (on sebelipase alfa) was rejected due to inability of liver biopsy (high risk of bleeding).
In this case quite fast progression of the metabolic orphan disease leaded to liver cirrhosis. Lysosomal acid lipase deficiency is potentially life-threatening diseases, such patient are needed careful observation. In Russia sebelipase alfa is not registered but could be possible chance for such patients, because there are no other treatment opportunities.