Chanarin-Dorfman Syndrome
DISEASE CARD
| Disease group | Keratinization Disorder |
|---|---|
| DISEASE NAME | Chanarin-Dorfman syndrome |
| Synonymous | Neutral lipid storage disease with ichthyosis, Triglyceride storage disease with impaired long-chain fatty acid oxidation, Ichthyotic neutral lipid storage disease, Dorfman-Chanarin syndrome, Chanarin-Dorfman disease, Ichthyosiform erythroderma with leukocyte vacuolation |
| Estimated prevalence | - |
| OMIM | 275630 |
| Inheritance | Autosomal Recessive |
| Gene (s) | ABHD5 (CGI58, NCIE2) (604780) |
Definition
Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive disorder of lipid metabolism characterized by multisystemic intracellular accumulation of triglycerides although plasma concentrations are normal. Clinical signs are variable and include ichthyosis, hepatomegaly, myopathy, cataracts and neurosensory deafness. It is a very rare disease mainly reported in consanguineous families from the Mediterranean and Middle-East. It is caused by mutations in the ABHD5 gene.
Clinical Description
The clinical presentation is variable due to multisystemic involvement. CDS infants typically present with generalized (non-bullous) ichthyosiform erythroderma (NCIE) at birth, with small, whitish scales. Collodion babies have been reported. Later, the face can be taut, scales can be larger and thicker and hyperkeratosis of palms and soles is frequent. Patients usually resemble mild to moderately severe NCIE or, rarely, pityriasis rubra pilaris.1
Hepatomegaly (pathological finding fatty liver) is often noticed on physical examination. The myopathy may be subtle and muscle creatine phosphokinase (CPK) can be elevated. Neurological impairment is also variable, developmental delay and mild mental retardation are the most frequent findings. Cataracts are the most frequent ocular signs, followed by (mild) ectropion. Further symptoms include short stature, sensorineural deafness and renal involvement.2 However, systemic manifestations of neural lipid storage disease (NLSD) may be clinically absent in infants, young children and even older patients.
Pathogenesis
Intracellular triglyceride metabolism is abnormal, with triglyceride accumulation in leukocytes, macrophages and fibroblasts. CDS is caused by mutations in the ABHD5 gene (also named CGI-58) on 3p25.3-p24.3. ABHD5 encodes the abhydrolase domain-containing protein 5, a protein with homology to the esterase/lipase/thioesterase subfamily. Its precise function in intracellular glyceride metabolism is unknown. The recycling of triglyceride-derived mono-or diacylglycerols into specific phospholipids is abnormal, altering the synthesis and degradation of cellular phospholipids.
Diagnosis
The diagnosis of CDS is based on the clinical presentation (skin changes) and presence of lipid-containing vacuoles in circulating granulocytes, eosinophiles and monocytes on peripheral blood smear. Using oil red-O, histological skin examination shows lipid droplets in the basal and granular cell layers, in sweat glands and in ducts. Liver and muscle biopsy can show fatty changes. Confirmation of the diagnosis can be yielded via detection of a mutation in the ABHD5 gene.
Treatment
The phenotype is markedly variable, and the treatment should be adapted to the individuals' manifestations. Systemic retinoids can be useful for severe skin manifestations.3 The usefulness of fat-restricted diets is uncertain. Reports show benefits of restriction of long‐chain fatty acids in the diet and promoting middle‐chain fatty acid intake for cutaneous changes and reduced lipid accumulation in other organs. The prognosis of CDS depends mainly upon the severity of hepatic involvement.4
References:
1. Eskiocak AH, Missaglia S, Moro L, Durdu M, Tavian D. A novel mutation of ABHD5 gene in a Chanarin Dorfman patient with unusual dermatological findings. 2019;18(1):232.
2. Verma SB, Mittal A, Wollina U, Eckstein GH, Gohel K, Giehl K. Chanarin-Dorfman syndrome with rare renal involvement. Br J Dermatol. 2017;176(2):545-548.
3. Israeli S, Pessach Y, Sarig O, Goldberg I, Sprecher E. Beneficial effect of acitretin in Chanarin-Dorfman syndrome. Clin Exp Dermatol. 2012;37(1):31-33.
4. Chander R, Varghese B, Garg T, Mittal S, Singh S. Dorfman-Chanarin syndrome in two female siblings: a case report and discussion on approach and management. Dermatol Online J. 2011;17(4):7.