Search for a rare disease
Wolman disease represents the most severe manifestation of lysosomal acid lipase deficiency. Milder phenotypes as a whole are referred to as cholesterol ester storage disease (see this term). The acid lipase enzyme plays an essential role in lysosomal hydrolysis of both esterified cholesterol and triglycerides of lipoproteic origin. In Wolman disease, the rarest form of acid lipase deficiency, these lipids accumulate in most tissues.
Approximately 50 cases have been reported in the literature.
The disease can sometimes present in the fetus (hepatomegaly, ascitis, calcified adrenal glands), but onset more typically occurs in the first weeks of life with abdominal distension and major or even massive hepatosplenomegaly (which can occur in the neonatal period) and sometimes ascitis. The presence of calcified adrenal glands (as revealed by radiography), is a nearly constant and very characteristic sign. Myelograms reveal the presence of foamy histiocytes, but this is not a specific findings. Children present with significant digestive disorders (such as vomiting and diarrhoea with steatorrhoea), which can lead to a sudden arrest of ponderal growth and progressive psychomotor degradation in the absence of specific neurological signs. Later, severe anemia and cachexia become apparent.
The enzymatic deficiency results from severe mutations of the acid lipase gene (LIPAor LAL), localised to 10q24-q25.
The diagnosis can be rapidly confirmed by measuring enzymatic activity in leucocytes (or fibroblasts), revealing an almost total deficiency.
Prenatal diagnosis can be performed by measuring enzymatic activity or by mutational analysis of chorionic villus samples.
The disease follows an autosomal recessive pattern of inheritance.
Management and treatment
At present, there is no specific treatment available for Wolman disease. However, in two published cases, a very early bone marrow or cord blood transplant seemed to provide good results after a 4-year follow-up. Although enzyme substitution and genetic therapy have shown promising results in the mouse LAL gene knock-out model, these studies can not necessarily be applied to Wolman disease as the mouse phenotype is closer to that of cholesterol ester storage disease.
Few children survive beyond one year of age.
- Clinical genetics review
- English (2016)