Prevalence of Lysosomal Acid Lipase (LAL) Deficiency in Non-obese Human Subjects with Persistent Unexplained Elevations in ALT

Abstract

Introduction: Lysosomal acid lipase (LAL) deficiency is an autosomal recessive disease with accumulation of cholesteryl esters and triglycerides in hepatocytes and cells of monocyte/macrophage lineage. This leads to microvesicular steatosis in the liver, leading to fibrosis and cirrhosis, as well as a dyslipidemia characterized by a high LDL and a low HDL cholesterol. Our aim was to evaluate non-obese adult subjects with unexplained elevation of liver transaminases for LAL deficiency. Methods: This is a prospective study aimed at finding the prevalence of LAL deficiency among non-obese adults with unexplained elevation of transaminases conducted in the period from May 2013 to May 2014 at a single urban institution. Inclusion criteria was defined as non-diabetic subjects age 18-70, with body mass index (BMI) less than 30, who had persistent unexplained elevation of ALT (>50 to <250) over a period of 6 months. Those subjects were identified via chart review of clinic patients within the last 4 years or prospectively from our gastroenterology clinic. Patients who met the inclusion criteria were contacted, and following formal consent, LAL enzyme assay test was performed by blood draw or fingerstick. Normal reference range for the test result was (40-600). Results: Eleven thousand, two hundred forty-nine patients with available BMI data were evaluated. Three thousand, one hundred fifty-three patients had at least 2 ALT results in the system. Six hundred of these patients were identified as having normal BMI (<30) and were non-diabetic with elevated ALT. Five hundred-eighty of these patients on detailed chart review had underlying liver disease or other medical explanations for the abnormal ALT value. Of the remaining 20 patients, 7 patients agreed to perform the test. Seven out of 7 (100%) of the patients tested had normal test result with a mean of 177.4, median 162. Conclusion: We evaluated an urban cohort of patients with elevated liver enzymes and low BMI for LAL deficiency. No patients were found with this rare disorder. Larger study sample would help in better evaluation of the prevalence of LAL deficiency in our population, and continued evaluation on perpatient basis is planned.Table 1Table 2