Wolman's disease: Clinical, biochemical and ultrastructural studies in an unusual case without striking adrenal calcification

Abstract

A case of Wolman's disease is described in a German infant who died at the age of 4 months. Hepatosplenomegaly, abdominal distention, gastrointestinal symptoms, dyserythropoietic changes in the bone marrow, but not adrenal calcification on X-ray were present. Stored lipid material could be demonstrated in liver, spleen, intestine, adrenals, thymus, kidneys, blood cells, but not in the central nervous system. Cholesterylesters and triglycerides were markedly increased in liver and spleen. Lysosomal acid lipase was found to be decreased in leucocytes and liver to less than 10% of normal, when measured with synthetic and natural substrates.

A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease.

“…This can be only accounted for by assuming that he is a compound heterozygote with a null allele inherited from his father. In summary, the data presented provide evidence that deletion of the codons for amino acids 254-277 in the LAL mRNA in combination with a null allele cause the clinical expression of CESD in our (3)(4)(5)(6). CESD is more benign and may not be detected until adulthood.…”

Wolman's Disease: The King Faisal Specialist Hospital and Research Centre Experience

“…Calcium soaps of the large amount of fatty acids become visible in the x-ray. 13,14 The diagnosis in our patients was first suspected through the plain x-ray film of the abdomen that outlined the calcified, enlarged adrenal glands (Figure 1). The CT of the abdomen confirmed the cortical deposits of calcium in the adrenal glands ( Figure 2), a finding which had been reported previously.…”

“…13 Hydrolysis of neutral fats and cholesterol esters in this necrotic mass takes place by other esterases that are normal in Wolman disease, e.g., by microsomal acid lipase and neutral esterase. Calcium soaps of the large amount of fatty acids become visible in the x-ray.…”

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

“…A key feature of WD is the enlargement and calcification of the adrenal glands, which can be confirmed via abdominal radiographs or histological examination [25]. Although adrenal calcification is a ubiquitous pathological feature of WD, some documented cases of WD patients do not have this affliction [26]. CT scans of the abdomen can reveal distended bowel loops [22] and biopsy of the small intestine can show infiltration of the lamina propria by foamy macrophages filled with cholesteryl esters and triglycerides.…”