Background

Lysosomal acid-lipase deficiency (LALD) is a rare genetic disorder causes due to LIPA gene mutations that affects lysosomal acid lipase enzyme. 

The two types as follows: 

Infantile LALD 

Late-onset LALD 

Infantile LALD occurs early in infancy it is more severe than late-onset LALD. While late-onset LALD occurs in mid-childhood. 

Both conditions involve enzyme deficiency leads to issues with lipid metabolism and proper breakdown of specific fats. 

Unused fats accumulate in cells, tissues, and organs causes disease symptoms due to lack of breakdown. 

People with lysosomal storage disorders are lack or insufficient enzymes to break down molecules for proper cell function. 

Epidemiology

Severe infantile LAL-D is rare with estimated incidence of 1 in 350000 individuals.  

Late-onset LAL-D is milder but still rare, with prevalence estimated at 1 in 40,000. 

Cholesteryl Ester Storage Disease rates higher in some European populations possibly due to founder effects or genetic drift. 

LAL-D prevalence in North America is consistent in worldwide population. Carrier frequencies estimated at 1 in 200 to 1 in 400 in the population. 

Anatomy

Pathophysiology

LAL enzyme in lysosomes breaks down cholesteryl esters to free cholesterol, fatty acids, and triglycerides. 

LIPA gene mutations result in decreased LAL enzyme activity to disrupt the breakdown of cholesteryl esters and triglycerides. 

Cholesterol esters and triglycerides build up in lysosomes of certain cell types. Lipid accumulation occurs in the liver, spleen, and adrenal glands that causes cellular dysfunction. 

Etiology

LAL-D results from mutations in the LIPA gene on chromosome 10. This gene produces the enzyme lysosomal acid lipase that breaks down cholesteryl esters and triglycerides. 

Inherited autosomal recessive LAL-D requires inherited two mutated LIPA gene copies for disease development. 

Mutations cause partial loss of LAL enzyme in Cholesteryl Ester Storage Disease. 

Genetics

Prognostic Factors

Certain mutations cause severe disease due to less enzyme function loss, while others lead to milder disease with partial enzyme activity. 

Symptoms may appear in later childhood, adolescence, or adulthood with LAL deficiency. 

Without treatment, early-onset infants face severe disease progression including malnutrition, liver failure, and adrenal insufficiency. 

Liver lesions strongly impact prognosis and treatment outcomes. 

Clinical History

It has severe infantile form known as Wolman Disease and late-onset form known as Cholesteryl Ester Storage Disease. 

Physical Examination

• Cardiovascular examination 
• Respiratory examination 
• Neurological Examination 

Age group

Associated comorbidity

Associated activity

Acuity of presentation

• Acute symptoms are: 
• Severe Feeding Difficulties 
• Vomiting and Diarrhea 
• Hepatosplenomegaly 
• Adrenal Calcification and Insufficiency 
• Chronic symptoms are: 
• Dyslipidemia 
• Hepatomegaly 
• Liver Dysfunction 
• Fatigue and Weakness 

Differential Diagnoses

• Gaucher disease 
• Familial hypercholesterolemia 
• Acid sphingomyelinase deficiency 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Sebelipase alfa is a human enzyme-replacement indicated for LAL-D treatment with identical amino acid sequence. 

HMG-CoA reductase inhibitors are used to lower LDL-C and reduce atherosclerosis risk. 

Lovastatin therapy improved lipid levels and decreased apo B lipoproteins secretion. 

Monitor hepatosplenic volume and screen for hepatocellular carcinoma in cirrhosis patients with serial liver imaging. 

Nonspecific beta-blockers should be used for those with esophageal varices to decrease bleeding risk. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

use-of-non-pharmacological-approach-for-lysosomal-acid-lipase-deficiency

Regular physical activity to improve overall well-being and reduce stress. 

Maintain clean and hygienic home environment to reduce the risk of infection. 

Proper awareness about LALD should be provided and its related causes with management strategies. 

Appointments with a physician and preventing recurrence of disorder is an ongoing life-long effort. 

Use of Enzyme Replacement Therapy

Sebelipase Alfa: 

It is a recombinant form of lysosomal acid lipase indicated to replace deficient enzymes in patients. 

Use of Lipid-Lowering Agents

Atorvastatin: 

It is used to reduce cholesterol levels and reduce cardiovascular risk in CESD cases. 

use-of-intervention-with-a-procedure-in-treating-lysosomal-acid-lipase-deficiency

Liver transplantation involves the surgical removal of the diseased liver and replacement with a healthy donor liver. 

Liver biopsy is performed to assess the degree of liver damage and cirrhosis in cases of CESD. 

use-of-phases-in-lysosomal-acid-lipase-deficiency

In the initial assessment phase, evaluation of patient history and laboratory test to confirm diagnosis. 

Pharmacologic therapy is effective in the treatment phase as it includes use of enzyme replacement therapy and lipid-lowering agents.  

In supportive care and management phase, patients should receive required attention such as lifestyle modification and intervention therapies. 

The regular follow-up visits with the physician are scheduled to check the improvement of patients along with treatment response. 

Medication

Future Trends

Media Gallary

References

Lysosomal Acid Lipase Deficiency – Endotext – NCBI Bookshelf (nih.gov)