Jordan’s anomaly in a case of Chanarin–Dorfman syndrome

Abstract

A 22–month–old boy presented with hepatomegaly, ichthyosis and asthma. Blood tests were normal except for a raised creatine kinase (CK) of 1077 iu/l, an elevated alanine transaminase of 216 iu/l and increased triglyceride levels of 3 mmol/l. A liver biopsy showed mild portal fibrosis with enlarged hepatocytes containing vacuoles and periodic acidSchiff stain revealed an excess of glycogen within some of the hepatocytes. This was felt to be in keeping with a glycogen storage disorder but further enzyme testing and mutation analysis did not confirm this diagnosis. Over the next 12 years he developed worsening ichthyosis (left) and complained of intermittent abdominal pains with occasional vomiting and altered bowel habit. His CK remained persistently raised and by the age of 14 years he had developed progressive fatigability with his exercise tolerance having reduced from 60 to 10 min over the previous year. At this stage a blood film was requested, which showed Jordan’s anomaly with marked vacuolation of all the white cells (right) raising the possibility of neutral lipid storage disorder as a diagnosis. Sequence analysis of the two genes PNPLA2 and ABHD5 was performed in the patient and his mother. Mutations in both genes have been described as causing forms of neutral lipid storage disease characterized by either myopathy (PNPLA2) or ichthyosis (ABHD5). PNPLA2 gene analysis did not provide evidence for disease-causing mutations. However, a c. 700C>T mutation was identified in the ABHD5 gene leading to a premature stop at amino acid Arg234. The patient was homozygous for this mutation and his mother was heterozygous. The patient was the first child born from a consanguineous marriage. He was diagnosed with Chanarin– Dorfman syndrome and commenced on a minimal long chain fat diet. Chanarin–Dorfman syndrome belongs to a group of autosomal recessive neutral lipid storage diseases and results from mutations in the ABHD5 gene. Abnormal triglyceride breakdown leads to the accumulation of triacylglycerols in leucocytes and in cells at multiple sites including the liver, gastrointestinal epithelium, muscle, skin and central nervous system. Patients present with diffuse nonbullous congenital ichthyosiform erythroderma and usually have a raised CK. They can also develop cataracts, neurosensory hearing loss, seizures, ataxia and hepatomegaly with elevated liver enzymes. This case emphasizes the importance of looking for Jordan’s anomaly in patients with congenital ichthyotic erythroderma.