National Lysosomal Acid Lipase Deficiency Study

Patients of 3 months to 18 years of age at the time of enrolment who have unexplained transaminase elevation (serum alanine aminotransferase (ALT) levels > 1.5 times the upper limit of normal) for more than 3 months and/or unexplained hepatomegaly or hepatosplenomegaly and/or obesity- unrelated hepatosteatosis and/or biopsy-proven cryptogenic fibrosis and cirrhosis and/or liver transplantation for cryptogenic cirrhosis will be included.

Potential participants will be invited for LAL enzyme analysis. Written informed consent will be obtained from the parents or guardians of the participants at the time of enrolment. Prospective and retrospective data will be collected. Complete family and medical history, physical examination and previously existing laboratory findings will be recorded on standard case reports form and up to 0.25 ml of blood will be drawn for LAL enzyme analysis. The blood obtained from participants will be spotted on filter paper, and dried blood spot sample (DBS) will be prepared. Finally, the dried blood spot sample will be sent to reference laboratory (NHS Greater Glasgow and Clyde, England) for LAL enzyme measurement within 1 week.

Inclusion criteria

• A male or female of 3 months to 18 years of age at the time of enrolment
• Patients who have unexplained transaminase elevation (serum ALT levels > 1.5 times the upper limit of normal) for more than 3 months
• Patients who have unexplained hepatomegaly or hepatosplenomegaly
• Patients who have obesity- unrelated hepatosteatosis
• Patients who have biopsy-proven cryptogenic fibrosis and cirrhosis
• Patients with liver transplantation for cryptogenic cirrhosis

Exclusion criteria

• A male or female < 3 months or > 18 years old
• Patients with obesity -related hepatosteatosis
• Patients with drug-induced hepatosteatosis ( such as aspirin, methotrexate, amiodarone, glucocorticoid, tamoxifen, 5-fluorouracil, valproate, nucleoid revers transcriptase inhibitors)
• Patients with organomegaly or transaminase elevation due to infectious causes (EBV, Brucella, cytomegalovirus, salmonella, malaria, leishmania etc), hæmato-oncological disease (hemolytic anemia, leukemia,lymphoma, malign or benign liver neoplasms), connective tissue disorders (SLE, RA), cardiac and vascular causes (heart failure, pericarditis, Budd-Chiari syndrome, portal vein thrombosis) and obesity.
• Patient with definitive diagnosed chronic liver disease such as chronic viral hepatitis (B, C hepatitis), autoimmune hepatitis, alpha-1 antitrypsin deficiency, Wilson disease, metabolic disorders.