The Frequency of Lysosomal Acid Lipase Deficiency in Children With Unexplained Liver Disease

Abstract

Objectives: Evidence suggests that lysosomal acid lipase deficiency (LAL-D) is often underdiagnosed because symptoms may be nonspecific. We aimed to investigate the prevalence of LAL-D in children with unexplained liver disease and to identify demographic and clinical features with a prospective, multicenter, cross-sectional study. Methods: Patients (aged 3 months–18 years) who had unexplained transaminase elevation, unexplained hepatomegaly or hepatosplenomegaly, obesity-unrelated liver steatosis, biopsy-proven cryptogenic fibrosis and cirrhosis, or liver transplantation for cryptogenic cirrhosis were enrolled. A Web-based electronic data collection system was used. LAL activity (nmol/punch/h) was measured using the dried blood spot method and classified as LAL-D (<0.02), intermediate (0.02–0.37) or normal (> 0.37). A second dried blood spot sample was obtained from patients with intermediate LAL activity for confirmation of the result. Results: A total of 810 children (median age 5.6 years) from 795 families were enrolled. The reasons for enrollment were unexplained transaminase elevation (62%), unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%), cryptogenic fibrosis and cirrhosis (6%), and liver transplantation for cryptogenic cirrhosis (<1%). LAL activity was normal in 634 (78%) and intermediate in 174 (21%) patients. LAL-D was identified in 2 siblings aged 15 and 6 years born to unrelated parents. Dyslipidemia, liver steatosis, and mild increase in aminotransferases were common features in these patients. Moreover, the 15-year-old patient showed growth failure and microvesicular steatosis, portal inflammation, and bridging fibrosis in the liver biopsy. Based on 795 families, 2 siblings in the same family were identified as LAL-D cases, making the prevalence of LAL-D in this study population, 0.1% (0.125%–0.606%). In the repeated measurement (76/174), LAL activity remained at the intermediate level in 38 patients. Conclusions: Overall, the frequency of LAL-D patients in this study (0.1%) suggests that LAL-D seems to be rare even in the selected high-risk population.

Lysosomal acid lipase deficiency in pediatric patients: a scoping review

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Lysosomal acid lipase activity in children with dyslipidemia and hepatic dysfunction

“…Nobody was enzyme deficient. It was reported that the enzyme activity between 0.15 -0.40 nmol/punch/hour could be related with LIPA gene heterozygous carriers [10]. But on the other hand, it was underlined that it was not reliable approach to identify the carriers [11].…”

Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease

“…One study screening for LALD based on clinical suspicion (hepatomegaly, a 1.5-fold increase in transaminases compared to reference limits, or dyslipidemia with or without splenomegaly, gastrointestinal dysfunction, or liver steatosis, fibrosis, or cirrhosis) successfully identified 19 cases in 4,174 using DBS ( Tebani et al, 2021 ). Another study screening 810 children in Turkey with either elevated transaminases for 3 months, hepatomegaly, or liver steatosis, fibrosis, or cirrhosis not explained by obesity or other causes by DBS found two LALD patients ( Kuloglu et al, 2019 ). A recent study published in this series of Frontiers in Genetics screened 669 Slovenian children with familial hypercholesterolemia and detected 3 cases of LALD homozygous for c.894G>A ( Sustar et al, 2022 ).…”