Screening for Lysosomal Acid Lipase Deficiency in a Lipid Clinic

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Lysosomal acid lipase deficiency (LAL-D) is a rare genetic disorder causing severe lipid accumulation.
• It affects multiple organs, leading to serious health issues like cirrhosis and early death.
• Early diagnosis is critical for initiating enzyme replacement therapy.

Purpose of the Study:

• To evaluate the effectiveness of a screening algorithm for LAL-D in patients with dyslipidemia or liver disease.
• To identify individuals who may benefit from further diagnostic testing for LAL-D.

Main Methods:

• Retrospective analysis of 2,018 adult and pediatric patient records.
• Application of a screening algorithm based on liver enzymes and lipid profiles (LDL-C, HDL-C).
• Enzymatic activity assay for LAL in dried blood spots for high-risk individuals.

Main Results:

• A screening algorithm identified 21 patients (0.92%) for LAL activity testing.
• Only eight patients completed the test, all with normal results.
• A posthumous diagnosis in a child confirmed LAL-D in their family, despite negative genetic variants in coding regions.

Conclusions:

• A clinical and laboratory-based algorithm can help select patients for LAL-D screening.
• LAL-D diagnosis is challenging due to its rarity and symptom overlap with other genetic dyslipidemias.
• LAL-D is often a diagnosis of exclusion, requiring thorough investigation after ruling out other conditions.