Wolman disease: Primary familial xanthomatosis

Clinical History

A consanguineous Egyptian couple brought their two month old male infant to the emergency department with vomiting, diarrhoea, abdominal distension and failure to thrive. He was born by operative delivery due to foetal distress and non-progressing labour, with birth weight of 3.2 kg. He lacked social smile and was unable to fix his gaze.

Imaging Findings

Ultrasound abdomen; performed as first line investigation showed hepatosplenomegaly. Both adrenals were enlarged however, their triangular configuration was maintained. The body and both limbs were identified separately and found to be highly echogenic with posterior acoustic shadowing, representing calcification -- pathognomonic of Wolman's disease. Plain X-ray abdomen confirmed bilateral calcified adrenals of triangular configuration. Soft tissue shadow of liver had displaced bowel loops inferiorly and caused bulging flanks.
The patient was given active supportive treatment immediately. On 3rd day of admission he was discharged on request . He died after 10 days without laboratory confirmation of lysosomal acid lipase deficiency; however, the mother was genetically screened and proved to be a carrier for Wolman disease providing evidence of genetic transmission of the disorder.

Discussion

Storage diseases are rare in occurrence but lethal in many instances. Rarer is the lipid storage disease. Wolman disease is an inherited, autosomal recessive, lysosomal fat storage disease. It is homozygous in inheritance and presents in infancy and is much more lethal in expression compared to its counterpart cholesteryl ester storage disease that is heterozygous and presents in early adult life [1]. Both male and female children are involved. Till now, less than 100 cases have been reported in the world. Among these, only 4 were reported from Saudi Arabia.
Chromosome 10 is involved with mutations at q24-q25 locus [2] and deficiency of the enzyme lysosomal acid lipase is the hallmark, leading to the fat accumulation in the body which results in the malfunction of various body systems.
Symptoms of the Wolman disease become apparent within the first few weeks or months of life and include vomiting, diarrhoea, abdominal distension, hypotonia, mental deterioration, anaemia, malnourishment and delayed developmental milestones etc. Hepatosplenomegaly and ascites may result in a distended abdomen. Laboratory findings usually include anaemia, thrombocytopenia, delayed coagulation, hypoalbuminaemia, hyperbilirubinaemia, hyperlipidaemia and deficiency of lysosomal acid lipase. Peripheral blood films show vacuolated lymphocytes while foamy histiocytes are seen on bone marrow aspiration [3]. Liver biopsy may show elliptical cholesterol clefts [4].
Radiological investigations include calcified adrenal glands on plain abdominal film, which are enlarged, maintaining normal triangular shape [5] compared to the calcification of the adrenal haematoma of perinatal age. The adrenal calcification secondary to haemorrhage is peripheral in location with normal adrenal size and shape. Ultrasound of the abdomen depicts hepatosplenomegaly and ascites. Liver may show increased echogenicity secondary to fat deposition. Adrenals are seen to be highly echogenic with posterior acoustic shadowing. CT scan shows hypo-dense liver and hyper-dense adrenals. MRI depicts signal loss on T1 and T2 in adrenals. Treatment options are few and none of them is curative. Bone marrow and cord blood transfusions have been used in some centres with promising results [6]. Gene transfer therapy is still under investigation [7].
Supportive treatment focuses on management of symptoms and provision of nutrition through intravenous route rather than oral feeding. Cessation of breast feeding, avoidance of lipid rich milk formulas is recommended. Hormone replacement therapy is considered in adrenal insufficiency.
Early and prompt diagnosis may help to initiate timely active management, which might delay the course of the disease and improve prognosis.

Differential Diagnosis List

Final Diagnosis

Wolman disease

URL:	https://www.eurorad.org/case/9106
DOI:	10.1594/EURORAD/CASE.9106
ISSN:	1563-4086