Chanarin–Dorfman syndrome caused by a novel splice site mutation in ABHD5

Abstract

Conflicts of interest: none declared. Sir, Chanarin–Dorfman syndrome (CDS; OMIM 275630) is a rare autosomal recessive metabolic disorder with deposition of cytoplasmic neutral lipid droplets in many cell types, in particular hepatocytes, keratinocytes and granulocytes. CDS is characterized by nonbullous congenital ichthyosiform erythroderma, hepatomegaly and varying developmental delay. Muscle weakness (or myopathy), ataxia, neurosensory hearing loss, subcapsular cataracts and nystagmus can be present.1 Expression of the syndrome is variable, but the diagnosis can be easily confirmed by a peripheral blood smear, which shows lipid droplets in granulocytes, known as Jordan’s anomaly.2 Mutations in the ABHD5 (formerly CGI‐58) gene on chromosome 3p21 have recently been identified as the genetic defect responsible for CDS.3 The ABHD5 gene product is a necessary cofactor for adipose triglyceride lipase (ATGL)‐mediated lipolysis4 and may also function in arachidonic acid metabolism. A 10‐year‐old boy with dry scaling skin was known to us from the age of 2 years onward. He was born from a full‐term normal pregnancy to consanguineous (first cousins) Turkish parents. No other family member had a similar skin disorder. The ichthyosis reportedly developed shortly after birth, but there was no history of erythroderma. On the most recent examination, the skin was slightly erythematous with fine scaling. The neck showed skin lichenification. On the trunk we saw nummular scaly patches with adherent fine grey‐white scaling (Fig. 1a, b). We observed a diffuse white lamellar scaling on the face with a mild lateral ectropion of the lower eyelids. The scalp also showed white scaling with a clear‐cut border following the hairline. The knees showed hyperkeratosis. The palms and soles were spared hyperkeratosis; nails and teeth were normal. He was under paediatric care for lactose intolerance and small stature. Several diagnoses had been entertained, including lamellar ichthyosis, erythrokeratodermia variabilis and, lately, nonbullous congenital ichthyosiform erythroderma. However, the last physical examination revealed hepatomegaly, suggestive of CDS. Ultrasound examination subsequently confirmed an enlarged liver with homogeneous normal echogenicity. When asked during the examination, both the patient and his parents could not recall him having had significant abdominal complaints. A peripheral blood smear showed leucocytes containing prominent lipid vacuoles (Jordan bodies; Fig. 1c), a pathognomonic finding in CDS. A skin biopsy was refused. Laboratory tests including full blood cell count, electrolytes and muscle enzymes were normal. Liver enzymes were slightly elevated: aspartate aminotransferase 89 IU L−1 (reference 15–35 IU L−1), alanine aminotransferase 81 IU L−1 (reference 15–35 IU L−1) and alkaline phosphatase 230 IU L−1 (reference 10–140 IU L−1).