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.

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.…”

Enfermedad hepática y dislipemia como manifestación de deficiencia de lipasa ácida lisosomal (LAL-D). Aspectos clínicos, diagnósticos y nuevo tratamiento. Actualización

“…6,7 El colesterol es elevado o normal con disminución de lipoproteínas de alta densidad (high-density lipoprotein cholesterol; HDL-C, por sus siglas en inglés) y aumento de las lipoproteínas de muy baja densidad (very low-density lipoprotein; VLDL, por sus siglas en inglés); los triglicéridos pueden estar normales o elevados. 8 La presencia de retardo madurativo y/o irritabilidad es secundaria a la desnutrición, al compromiso general y a la hospitalización, ya que la enfermedad no compromete el sistema nervioso central. 9 La evolución natural de esta forma clínica lleva a la muerte en el primer año de vida.…”