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Q1: What are the radiological findings and findings on peripheral smear and bone marrow?
The radiograph (fig 2; see p 567) shows symmetric stippled calcific deposits in both adrenals. On an abdominal ultrasound (fig 3; see p 567) this appears like radio-opaque deposits. The peripheral smear shows lymphocytes containing small vacuoles (fig 1; see p 567). Bone marrow aspiration shows lymphocytes and many macrophages with vacuolated cytoplasm and a foamy appearance (fig 4; see p 567), similar to that seen on a peripheral smear.
Q2: What is the diagnosis? What are the possible differential diagnoses?
The diagnosis is Wolman’s disease, a characteristic feature of which is diffuse calcification of symmetrically enlarged adrenal glands.1 From the clinical presentation in the above case a differential diagnosis would include any of the other commoner storage disorders like Gaucher’s and Niemann-Pick disease, congenital leukaemias, osteopetrosis, and histiocytosis. Foamy cells as in fig 4 (see p 567) are seen in Pompe’s and Niemann-Pick disease. Calcification of adrenals is not seen in these two conditions. Idiopathic adrenal calcification, adrenal haemorrhage, tumours, or granulomas are other causes of adrenal calcification; however these are usually unilateral.
Q3: What is the prognosis and treatment of this condition?
The prognosis is usually bad and patients do not survive beyond one year, most succumbing to gastrointestinal and haematological complications. The treatment is bone marrow transplantation; however, other experimental modalities of treatment like lovastatin and a diet free of hydrophobic esters, in which cholesterol and essential fatty acid are bound to protein, have been tried with varying results.
Wolman’s disease is an autosomal recessive lipid storage disorder secondary to a deficiency of cholesterol ester hydrolase resulting in accumulation of cholesterol esters in all organs especially the liver, bone marrow, and spleen.1,2 The first report described the disease in three siblings who were Persian Jews.1 The original belief that the disease was confined to one ethnic group has been negated as the disease has been reported subsequently in a wide variety of races and ethnic groups. The genetic defect is on the long arm of chromosome 10 (10q23.2–10q23.3).3 Cholesterol ester hydrolase hydrolyses cellular cholesterol esters and triglycerides after uptake of low density lipoproteins. Acid lipase deficiency results in intralysosomal storage and abnormal regulation of cellular cholesterol.2 Near total deficiency of acid lipase is found in tissues, leucocytes, and cultured fibroblasts from these patients.
Infants usually present with failure to thrive, developmental delay, diarrhoea, and hepatosplenomegaly. Adrenal failure is relatively rare.3 The neurological manifestations include mental retardation, spasticity and clonus, which though at first mild, have been known to progress rapidly.4 The extent of the neurological disease is not very clear as these infants usually succumb to gastrointestinal and haematological complications and die early. The vomiting and diarrhoea results from severe damage to the microvilli and the accumulation of foam cells in the intestinal mucosa.5 A thickened bowel wall may also be a finding on ultrasound.6
Anaemia usually occurs by the sixth week and becomes progressively severe, though thrombocytopenia is relatively rare.7 This is because of replacement of marrow by foamy macrophages. There may be a papulovesicular rash on the face. There are a few patients with persistent jaundice as the presenting complaint. In the liver, this disorder is associated with increased fibrosis and ultimately cirrhosis. Liver function tests are normal unless hepatic fibrosis is extensive and the serum triglycerides and cholesterol are usually always normal in these patients.1,4,8 The enlarged liver has a distinct orange appearance on postmortem examination.
Cholesterol ester storage disorder is a milder allelic form of this disease.9 The residual enzymes are greater and onset is delayed until early adulthood. They usually present with hepatosplenomegaly and premature arteriosclerosis. Adrenal calcification is rare. Carriers for this disease have been detected and prenatal diagnosis, based on acid lipase activity in chorionic villi and in cultured amniotic cells using cholesterol oleate as a substrate, is possible.