Wolman disease

The called Wolman Disease, also Wolman syndrome or Crohn Wolman, is an extremely rare autosomal recessive lysosomal storage disease.

Etiology and Genetics

A defect in the enzyme lysosomal acid lipase (LAL lysosomal acid lipase = ) results in affected patients to an accumulation ( storage) of cholesterol esters and triglycerides. The gene coding for the acid lipase gene locus is located on chromosome 10 q23.2 - 23.3. It consists of ten exons. Nonsense and missense mutations, and frameshifts and skipping exons, can lead to a loss of function of the gene product LAL.

There can not attain the lipids from the cytoplasm through the lysosome, in a loss of function of the lysosomal acid lipase, the control circuit for the regulation of the intracellular cholesterol concentration is interrupted. The low concentration of intracellular cholesterol in turn leads to the upregulation of the endogenous synthesis of cholesterol and LDL receptor activity. The lysosome receives the endocytosed cholesterol. Due to the endogenous cholesterol synthesis, the cells are overloaded with cholesterol, thereby forming lipid vacuoles. These cause a loss of function of the cells, fibrosis, and ultimately cell death.

At the milder end, also extremely rare, cholesterol ester storage disease ( CESD ), however, a residual activity of lysosomal acid lipase is still available. This residual activity is sufficient for the cholesterol ester degradation in the CESD - except in the liver - largely to accomplish.

The genetic defect is inherited as an autosomal recessive trait. There are correlations between genotype and phenotype.

Symptoms

The symptoms are already present in the first days of life. These are gastrointestinal symptoms (vomiting and diarrhea ), expanded body atrophy and anemia, and an enlarged liver and spleen ( hepatosplenomegaly ). Patients have increased by necrosis and calcified adrenal glands.

Prevalence and prognosis

The Wolman 's disease is extremely rare. The prevalence is estimated at 1:700.000. They usually leads already in early childhood, usually at the age of three to six months, in each case in the first year of life, death.

Therapy

There is currently no specific treatment for Wolman 's disease. Treatment is symptomatic, such as by the administration of HMG-CoA reductase inhibitors, inhibitors of cholesterol and apolipoprotein B synthesis.

Various clinical programs have successfully performed in recent years to the development of enzyme replacement therapies for lysosomal storage diseases different. The affected enzyme is regularly supplied from external and can reverse or reduce the symptoms.

First clinical studies to develop an enzyme replacement therapy for the lysosmale acid lipase (LAL ) are established and recruit patients worldwide.

First description

The Wolman 's disease was in 1961 by the Israeli neuropathologist Moshe Wolman ( 1914-2009 ) first described. He is the namesake of the disease.