Chanarin–Dorfman syndrome: clinical/genetic features and natural history in six Pakistani patients

Abstract

Abstract Background Chanarin–Dorfman syndrome (CDS; OMIM # 275630) is a rare neutral lipid storage disorder caused by mutation in ABHD5 (a/b hydrolase domain containing 5″) a cofactor for adipose triglyceride lipase (ATGL) resulting in intracellular accumulation of triacylglycerol (TG) in numerous body tissues. It is an autosomal recessive disorder mutation in ABHD5 that causes the partial or total loss of ATGL activation, leading to the accumulation of TG inside lipid droplets. We aim to assess the clinical and biochemical manifestations, diagnosis, follow-up and genotype–phenotype correlations in six Pakistani pediatric patients with CDS. Results Six male patients with mean age 15 months (9–24 months) diagnosed as CDS on the basis of non-bullous ichthyosiform erythroderma, hepatomegaly and Jordans bodies in peripheral smear. We identified two novel mutations in ABHD5 gene (c.338G > T and c.730_731insA). These mutations have a pathogenic and damaging influence on the ABHD5 protein structure and function. During the 2 year clinical follow-up one patient died of severe chest infection; he had severe phenotype. There is no genotype–phenotype correlation in CDS. Therapy with low fat diet, MCT oil, Vit E and ursodeoxycholic acid has promising results in CDS. Conclusion Non-bullous ichthyosiform erythroderma, steatohepatitis and Jordan’s anomaly are consistent findings in all cases of CDS. It is suggested that an accurate diagnosis of CDS should be based on combination of clinical features and pathognomonic ABHD5 mutations. More studies should be carried out to identify population-specific genetic mutations for the rapid and cost-effective diagnosis of CDS.