Hepatobiliary and pancreatic: Dorfman–Chanarin syndrome

Abstract

The Dorfman-Chanarin syndrome is a rare, inherited disorder of lipid metabolism. Early in life, the most prominent clinical feature is dryness and scaling of the skin (ichthyosis). This has been attributed to the presence of lipid droplets in the basal layer of the epidermis that promotes clefts between the granular layer and the horny layer. Additional clinical features are variable but include myopathy, mental retardation, growth retardation, sensorineural deafness and cataracts. Approximately 60% of patients with Dorfman-Chanarin syndrome have a fatty liver, usually with abnormal liver function tests, and some progress to hepatic fibrosis and cirrhosis. An important diagnostic feature is the presence of lipid vacuoles in peripheral blood leukocytes, a finding often referred to as Jordan's anomaly. These vacuoles can be identified in 25% of granulocytes and monocytes. The genetic basis for Dorfman-Chanarin syndrome has been identified as mutations in the ABHD5 (abhydrolase domain containing 5) gene, although the precise function of the enzyme encoded by the gene remains unclear.The features of the Dorfman-Chanarin syndrome illustrated below were from a 15-month-old boy who was investigated because of ichthyosis. He had an enlarged liver and spleen on physical examination. A blood count revealed mild anemia (hemoglobin, 9.5 g/L) while a peripheral blood smear showed vacuoles within the cytoplasm of circulating granulocytes (Fig. 1). Liver function tests were abnormal and sweat chloride levels were elevated (110 mmol/L; N < 70 mmol/L). The latter was attributed to ichthyosis as he did not have one of the common genetic mutations associated with cystic fibrosis. A liver biopsy revealed macrovesicular steatosis in most of the hepatocytes and an excess of fibrous tissue in portal areas (Fig. 2). The histological appearance was that of nonalcoholic steatohepatitis. In the Dorfman-Chanarin syndrome, progression of steatohepatitis to cirrhosis may occur at a relatively early age (< 10 years).

Renal Involvement as a Rare Complication of Dorfman–Chanarin Syndrome: A Case Report

“…Clinically, a generalized erythrodermic congenital nonbullous ichthyosis with fine, white scales involving the flexures, scalp and face, hyperkeratosis on the palms and soles were observed in our patient. This has been attributed to the presence of lipid droplets in the basal layer of the epidermis that promotes clefts between the granular layer and the horny layer (9).…”

“…Involvement of the liver (64%), spleen (24%), muscle (61%), and central nervous system (30%) is frequent. Cardiac, ocular and intestinal anomalies, hearing loss, short stature, and microcephaly are other possible manifestations (2,3,9–12). In DCS, progression of steatohepatitis to cirrhosis may occur at a relatively early age (<10 years) (13).…”

A case with full clinical manifestations of Dorfman-Chanarin syndrome

“…The present case was also born of consanguineous marriage. In literature, there are five cases of Turkish origin reported with DCS characterized by ichthyosis, lipid vacuoles in the leucocytes and also liver involvement has observed in three cases of them [6,8,10]. The wide spread tissue deposition of neutral lipids result in a broad spectrum of systemic manifestations.…”

“…To our knowledge, 45 cases of DCS have been reported in the worldwide [4][5][6][7][8]. The majority of patients were of Middle-Eastern origin [2,9] and five of the cases were Turkish origin [6,8,10]. Herein, we report a Turkish man with the complete syndrome in addition to organ calcifications who described family history of ichthyosis.…”

“…Clinical manifestations of this syndrome related with the affected organs are; ichthyosis, myopathy, liver steatosis, sensorineural hearing loss, growth retardation, mental retardation, cataract and a variety of neurological symptoms. To our knowledge, 45 cases of DCS have been reported in the worldwide [4][5][6][7][8]. The majority of patients were of Middle-Eastern origin [2,9] and five of the cases were Turkish origin [6,8,10].…”