Clinical Features of Lysosomal Acid Lipase Deficiency

Abstract

Objective:The aim of this study was to characterize key clinical manifestations of lysosomal acid lipase deficiency (LAL D) in children and adults.Methods:Investigators reviewed medical records of LAL D patients ages ≥5 years, extracted historical data, and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset.Results:A total of 49 patients were enrolled; 48 had confirmed LAL D. Mean age at first disease-related abnormality was 9.0 years (range 0–42); mean age at diagnosis was 15.2 years (range 1–46). Twenty-nine (60%) were male patients, and 27 (56%) were <20 years of age at the time of consent/assent. Serum transaminases were elevated in most patients with 458 of 499 (92%) of alanine aminotransferase values and 265 of 448 (59%) of aspartate aminotransferase values above the upper limit of normal. Most patients had elevated low-density lipoprotein (64% patients) and total cholesterol (63%) at baseline despite most being on lipid-lowering therapies, and 44% had high-density lipoprotein levels below the lower limit of normal. More than half of the patients with liver biopsies (n = 31, mean age 13 years) had documented evidence of steatosis (87%) and/or fibrosis (52%). Imaging assessments revealed that the median liver volume was ∼1.15 multiples of normal (MN) and median spleen volume was ∼2.2 MN. Six (13%) patients had undergone a liver transplant (ages 9–43.5 years).Conclusion:This study provides the largest longitudinal case review of patients with LAL D and confirms that LAL D is predominantly a pediatric disease causing early and progressive hepatic dysfunction associated with dyslipidemia that often leads to liver failure and transplantation.

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

“…Elevated LDL-cholesterol, triglycerides, and serum total cholesterol are also present in patients [16, 17]. As mentioned previously, WD may be differentiated from CESD based on their differences in disease progress as well as the functional level of LAL in peripheral tissues.…”

Identification of rare diseases by screening a population selected on the basis of routine pathology results—the PATHFINDER project: lysosomal acid lipase/cholesteryl ester storage disease substudy

“…PROCAM recruited a cohort of 4043 men aged 40–65 years and 1333 women aged 55–65 years to study cardiovascular disease events. The frequency of the E8SJM mutation (c.894G>A;p.delS275_Q298; IVS8) was 10 in 2023 giving an estimated frequency for the E8SJM mutation of 0.0025 (1 in 400) 4. This mutation is found in ∼50% of patients with LALD.…”

Liver disease and dyslipidemia as a manifestation of lysosomal acid lipase deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. An update

“…6,7 Cholesterol levels are elevated or normal with reduced high-density lipoproteins (HDL) and increased very low-density lipoproteins (VLDL); triglycerides may be normal or elevated. 8 Developmental delay and/or irritability are secondary to malnutrition, overall compromise, and hospitalization resulting from the central nervous system involvement caused by this disease. 9 The natural course of this clinical form results in death in the first year of life.…”