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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 4  |  Page : 799-801
Dorfman-Chanarin syndrome: A rare neutral lipid storage disease


Department of Pediatrics, Medical College, 88, College Street, Kolkata, West Bengal, India

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Date of Web Publication27-Oct-2010
 

   Abstract 

Dorfman-Chanarin syndrome is a rare neutral lipid storage disorder characterized by ichthyosis, lipid vacuolations in peripheral leucocytes, and multisystem involvement. It is an autosomal recessive disorder caused by mutations in the CGI-58 gene. A total of 42 cases have been reported worldwide till February 2009 out of which 4 have been previously reported from India. We report a case of a 20-month-old male with congenital ichthyosis, organomegaly, and bilateral cryptorchidism. Examination of the peripheral smear revealed lipid vacuoles in the leucocytes consistent with Jordan's anomaly, which was confirmed by transmission electron microscopy. Liver biopsy revealed micronodular cirrhosis with macrovesicular steatosis while skin biopsy showed ichthyosis vulgaris. Dorfman-Chanarin syndrome was diagnosed on the basis of clinical and laboratory criteria with certain unreported manifestations. Dietary modifications were instituted and followed up after 1 year with promising results. This emphasizes the importance of neonatal screening for lipid vacuolations in peripheral blood in all cases of congenital ichthyosis.

Keywords: CGI-58, Dorfman-Chanarin syndrome, ichthyosis, Jordan′s anomaly, leucocyte vacuoles

How to cite this article:
Mitra S, Samanta M, Sarkar M, Chatterjee S. Dorfman-Chanarin syndrome: A rare neutral lipid storage disease. Indian J Pathol Microbiol 2010;53:799-801

How to cite this URL:
Mitra S, Samanta M, Sarkar M, Chatterjee S. Dorfman-Chanarin syndrome: A rare neutral lipid storage disease. Indian J Pathol Microbiol [serial online] 2010 [cited 2019 Sep 15];53:799-801. Available from: http://www.ijpmonline.org/text.asp?2010/53/4/799/72098



   Introduction Top


Dorfman-Chanarin syndrome (DCS) is a rare autosomal recessive neutral lipid storage disorder. [1] It is characterized by congenital ichthyosis, lipid vacuoles in peripheral leucocytes (Jordan's anomaly), and multisystem involvement. [2] A total of 42 cases have been reported worldwide till February 2009. [3] Out of them, four have been previously reported from India. [4],[5],[6],[7] Here we present a case of DCS with certain unreported clinicopathological features with a 1-year follow-up experience.


   Case Report Top


A 20-month-old male presented with generalized scaling since birth. The scaling was most intense at birth but gradually became less prominent with age. No erythema, bullous lesions, or erosions had appeared at any point of time. There was also gradual swelling of the abdomen over the past 1 year. There was no history of any feeding difficulties, jaundice, dark urine, or clay-colored stools. There was no history of visual loss, abnormal ocular movements, or hearing defects. There was no limb weakness or any focal neurodeficits. He was the first child born out of second degree consanguineous marriage. There was no previous pregnancy loss and no history of maternal infection, exposure to drugs, radiation, smoking, or alcohol during pregnancy. No other family member had been similarly affected.

Cutaneous examination revealed generalized scaling with no erythema [Figure 1]. The scales were fine, whitish, nonpruritic involving the whole body including the face and scalp. Flexural surfaces showed corrugation and hyperpigmentation. The eyelids showed mild ectropion. Ocular examination performed under general anesthesia was within normal limits. Audiological examination using brainstem-evoked response audiometry was normal.
Figure 1 :Generalized nonerythematous scaling

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Abdominal examination revealed a 10-cm firm, nontender hepatomegaly with mild splenomegaly. There was bilateral cryptorchidism [Figure 2]. Nervous and musculoskeletal system examinations were normal. A detailed developmental assessment revealed that the developmental age was 12-15 months in all aspects of development indicating a global developmental delay. Anthropometry revealed that the length-for-age, weight-for-age, and head circumference-for-age were well below the third percentile according to the CDC (Centre for Disease Control) charts. The weight-for-length was at the 10th percentile curve.
Figure 2 :Bilateral cryptorchidism

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On investigation, complete blood counts were normal but the peripheral smear showed prominent leucocytic vacuolations involving the neutrophils, eosinophils, and monocytes that remained optically clear on Leishman's and Sudan Black B stains (Jordan's anomaly) [Figure 3]. Liver functions tests revealed mildly elevated aspartate aminotransferase (137 IU/L) and alkaline phosphatase (537 IU/L) and a normal prothrombin time (14 s; control 12 s). Lipid profile revealed elevated serum triglycerides (176 mg%; 95th percentile for age and sex is 99 mg%) and low serum cholesterol (91 mg%; 5th percentile for age and sex is 114 mg%). [8] Creatine phosphokinase and coagulation profile were normal. Chest and skeletal X-rays were normal. Ultrasound abdomen revealed hepatomegaly with fatty change, along with mild splenomegaly. Skin biopsy showed hyperkeratosis with a diminished granular cell layer suggestive of ichthyosis vulgaris. Liver biopsy revealed micronodular cirrhosis with macrovesicular steatosis [Figure 4]. Transmission electron microscopy was done from the peripheral blood buffy coat preparation fixed in paraformaldehyde-glutaraldehyde, postfixed in osmium tetroxide (original magnification ×16,500; bar, 1 u). It revealed intracytoplasmic extralysosomal non-memebrane-bound neutral lipid within the granulocytes (Jordan's anomaly) [2][Figure 5]. The enzyme study for the plasma beta-glucosidase activity was normal. Peripheral smears from both parents were also normal.
Figure 3 :Peripheral blood smear stained with Leishman's stain showing optically clear vacuoles (Jordan's anomaly), original magnification ×1000

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Figure 4 :Photomicrograph of liver biopsy stained with H and E showing micronodular cirrhosis with macrovesicular steatosis (original magnification ×100)

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Figure 5 :Transmission electron microscopy of the peripheral blood buffy coat preparation fixed in paraformaldehyde-glutaraldehyde, postfixed in osmium tetroxide showing intracytoplasmic, extralysosomal, non-membrane-bound neutral lipid vacuoles (transmission electron micrograph, original magnification ×16,500; bar, 1 u)

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The patient was henceforth put on a low-fat with medium chain triglycerides, low-protein, high-carbohydrate diet with ursodeoxycholic acid (20 mg/kg/day) and vitamin E (10 mg/kg/day) along with 40% urea cream for local application. [2],[5],[6] After 1 year of follow-up, the patient now can walk without support and climb stairs one step at a time, and can speak simple sentences corresponding to a developmental age of around 24 months. Clinically, he now has a liver size of only 4 cm below the costal margin, no splenomegaly, and markedly diminished ichthyosis. Liver functions are normal but serum triglycerides (158 mg%) still remain beyond the 95th percentile for age.


   Discussion Top


The characteristic clinical and laboratory findings in our patient fulfilled the diagnostic criteria for DCS. [2],[5] Possible differentials that may present with vacuolated leucocytes include ichthyotic (multiple sulfatase deficiency, ichthyosis-sclerosing cholangitis syndrome) and degenerative disorders (systemic carnitine deficiency, Refsum disease, Wolman disease). [2] But the presence of congenital ichthyosis with systemic neutral lipid deposition is characteristic of DCS. It occurs due to the mutation of both copies of the ABHD5 (abhydrolase domain containing 5 (CGI-58)) gene traced to chromosome 3p21. [6] The CGI-58, a 39 kDa protein of the alpha-beta hydrolase subfamily coordinates with lipolytic factors like perilipin and activates a rate limiting lipase ATGL in the adipocytes. [9] The truncation of the CGI-58 protein leads to a significant loss of lipase-thioesterase activity and consequent defect in the neutral lipid breakdown. [10] This leads to a variety of clinical features like ichthyosis, steatohepatitis and liver cirrhosis, myopathy, growth retardation, sensorineural deafness, cataract, strabismus, and retinal dysfunction, and neurological abnormalities like nystagmus, ataxia, areflexia, hypotonia, marked proximal muscle weakness, ptosis, cranial nerve involvement, mental retardation, and psychiatric disorders. [2],[7],[11],[12] Hemangiomas, splenomegaly, neural tumors of the mediastinum, microcephaly, small ears, rickets, renal involvement, and eccrine gland vacuolations have also been rarely reported. [6],[7],[10],[13],[14],[15]

Apart from the ones already mentioned above, our case had certain novel features. Reports suggest that the variety of congenital ichthyosis that occurs in DCS is usually congenital ichthyosiform erythroderma and rarely lamellar ichthyosis. [6] But here we found ichthyosis vulgaris with prominent flexural surface involvement. Also, the association of cryptorchidism has never been reported in a case of DCS.

The rapid progression of steatohepatitis to cirrhosis has been found to occur in DCS. [2] There is no documented evidence that dietary modifications alter the course of the disease. But favorable results have been obtained in our case till date. Further follow-up studies are required. This emphasizes on the need to screen every newborn with congenital ichthyosis for systemic lipid storage disorders and provide genetic counseling to the parents.


   Acknowledgment Top


We thank the Institute of Hematology and Transfusion Medicine, Medical College Kolkata, for helping us in the advanced hematological investigations and providing pictures of the same.

 
   References Top

1.Chanarin-Dorfmann Syndrome; Online Mendelian Inheritance in Man, OMIM (TM). Johns Hopkins University, Baltimore, Md. MIM Number 275630. Available from: http://www.ncbi.nlm.nih.gov/omim/. [last accessed on 2009 Oct 24].  Back to cited text no. 1
    
2.Srinivasan R, Hadziζ N, Fischer J, Knisely AS. Steatohepatitis and unsuspected micronodular cirrhosis in dorfman-chanarin syndrome with documented ABHD5 mutation. J Pediatr 2004;144:662-5.  Back to cited text no. 2
    
3.Selimoglu MA, Esrefoglu M, Gul M, Gungor S, Yildirim C, Seyhan M. Chanarin Dorfman syndrome: Clinical features of a rare lipid metabolism disorder. Pediatr Dermatol 2009;26:40-3.  Back to cited text no. 3
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4.Nanda A, Sharma R, Kanwar AJ, Kaur S, Dash S. DorfmanChanarin syndrome. Int J Dermatol 1990;29:349-51.  Back to cited text no. 4
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5.Tullu MS, Muranjan MN, Save SU , Deshmukh CT, Khubchandani SR, Bharucha BA. Dorfman-Chanarin syndrome: A rare neutral lipid storage disease. Indian Pediatr 2000;37:88-93.   Back to cited text no. 5
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6.Gupta P, Kaur G. Chanarin Dorfman syndrome neonatal diagnosis and 3-year follow-up. Indian Pediatr 2005;42:1054-5.  Back to cited text no. 6
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7.Gandhi V, Aggarwal P, Dhawan J, Singh UR, Bhattacharya SN. Dorfman-Chanarin syndrome. Indian J Dermatol Venereol Leprol 2007;73:36-9.  Back to cited text no. 7
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8.Neal WA. Disorders of Lipoprotein Metabolism and Transport. In: Kliegman RM, Jenson HB, Behrman RE, Stanton BF, editors. Nelson Textbook of Pediatrics, 18 th ed, Vol 1, Part 1-16;12. Philadelphia. Saunders 2007. p. 589  Back to cited text no. 8
    
9.Yamaguchi T, Osumi T. Chanarin-Dorfman syndrome: Deficiency in CGI-58, a lipid droplet-bound coactivator of lipase. Biochim Biophys Acta 2009;1791:519-23.  Back to cited text no. 9
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10.Akiyama M, Sawamura D, Nomura Y, Sugawara M, Shimizu H. Truncation of CGI-58 protein causes malformation of lamellar granules resulting in ichthyosis in Dorfman-Chanarin syndrome. J Invest Dermatol 2003;121:1029-34.  Back to cited text no. 10
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11.Ronchetti A, Prati D, Pezzotta MG, Tavian D, Colombo R, Callea F, et al. Severe steatohepatitis in a patient with a rare neutral lipid storage disorder due to ABHD5 mutation. J Hepatol 2008;49:474-7.  Back to cited text no. 11
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12.Gupta P, Dhingra KK, Kawatra V, Singh T, Yadav S. Dorfman-Chanarin syndrome with cirrhosis. Pathology 2008;40:650-3.  Back to cited text no. 12
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13.Taskin E, Akarsu S, Aygun AD, Ozlu F, Kilic M. Rickets with Dorfman-Chanarin syndrome. Acta Haematol 2007;117:16-9.   Back to cited text no. 13
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14.Aksu G, Kalkan Ucar S, Bulut Y, Aydinok Y, Sen S, Anal O, et al. Renal involvement as a rare complication of Dorfman-Chanarin syndrome: A case report. Pediatr Dermatol 2008;25:326-31.  Back to cited text no. 14
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15.Pahwa M, Kar R, Singh A, Goel A, Ramesh V, Jain R. Chanarin-Dorfman syndrome with eccrine gland vacuolation: A case report. Int J Dermatol 2008;47:1257-9.  Back to cited text no. 15
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Correspondence Address:
Souvik Mitra
618, Block "O," New Alipore, Kolkata - 700 053, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.72098

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