|Year : 2020 | Volume
| Issue : 1 | Page : 42-44
Harshal Ranglani, Pankaj Shukla
Department of Dermatology, Goa Medical College, Bambolim, Goa, India
|Date of Submission||19-Sep-2019|
|Date of Decision||23-Oct-2019|
|Date of Acceptance||27-Nov-2019|
|Date of Web Publication||24-Dec-2019|
Dr Harshal Ranglani
Department of Dermatology, Goa Medical College, Bambolim - 403 202, Goa
Source of Support: None, Conflict of Interest: None
Chanarin–Dorfman syndrome is a rare, autosomal recessive disorder of lipid metabolism, occurring due to mutation of abhydrolase domain containing 5 gene, resulting in the accumulation of triglycerides in the skin, muscles, liver, and other organs. This disorder is clinically characterized by the presence of generalized ichthyosis along with organomegaly and other systemic features, while evidence of vacuolated neutrophils and eosinophils on the peripheral blood smear confirms the diagnosis. We report a 3-year-old girl with Chanarin–Dorfman syndrome to generate awareness about this rare condition.
Keywords: Chanarin–Dorfman syndrome, ichthyosis, inherited ichthyosis, Jordan's anomaly
|How to cite this article:|
Ranglani H, Shukla P. Chanarin–Dorfman syndrome. Indian J Paediatr Dermatol 2020;21:42-4
| Introduction|| |
Chanarin–Dorfman syndrome is a rare, autosomal recessive disorder of lipid metabolism, clinically presenting with ichthyosis along with varied systemic changes.
| Case Report|| |
A 3-year-old girl, first by birth order, born of nonconsanguineous parentage was presented to us with generalized redness and scaling over the body since birth. It was progressive, punctuated with episodic winter exacerbations. There was a history of collodion membrane at birth. Subsequently, her abdomen distended progressively over the past 2 years. Family history was noncontributory. There was no history of seizures, photophobia, vomiting, or photosensitivity.
On examination, the patient was short for age (<3rd percentile). She had coarse facial features, thick lips, and protruding tongue. Firm, nontender hepatomegaly was elicited. Central nervous system examination revealed delayed speech and motor milestones, while ocular examination demonstrated bilateral nystagmus, squint, and cataracts.
Generalized erythema with fine scaling over the trunk and upper limbs was noted on cutaneous examination [Figure 1] and [Figure 2], along with thick, large, brown, polygonal, adherent scales on the lower limbs [Figure 3]. Lichenification was observed on the axillae, elbow, and knee flexures as well as the neck [Figure 4]. Hair, nail, and mucosae were spared.
|Figure 2: Generalized scaling over the trunk with mild background erythema. Scales are white, fine, and loosely adherent|
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|Figure 3: Presence of thick, brownish, adherent scales on both lower limbs. Few appear large and polygonal|
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|Figure 4: Presence of marked lichenification and hyperpigmentation in the axillae, giving it a corrugated appearance|
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Differential diagnosis of nonbullous congenital ichthyosiform erythroderma, lamellar ichthyosis, and autosomal recessive syndromic ichthyosis (including Chanarin–Dorfman syndrome and Refsum syndrome) was considered.
Laboratory investigations were within normal limits, except for the presence of lymphocytosis. Peripheral blood smear examination demonstrated multiple cytoplasmic vacuoles within the neutrophils and eosinophils (Jordan's anomaly) [Figure 5]. Serum glutamic-oxaloacetic transaminase and serum glutamic pyruvic transaminase levels were 132 and 160 IU/ml, respectively. Creatinine kinase and lactate dehydrogenase levels were within normal limits. Thyroid and renal function tests were normal. Serum triglyceride level was elevated (335 mg/dl) with normal cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) levels. Abdominal ultrasound revealed hepatomegaly with fatty changes. Brainstem evoked response audiometry revealed sensorineural deafness. Skin histology demonstrated compact orthokeratosis with slight acanthosis and papillomatosis, without any epidermolytic changes [Figure 6]. Due to resource constraints, genetic analysis was not performed.
|Figure 5: Presence of multiple vacuoles in the cytoplasm of neutrophils on peripheral smear: Jordan's anomaly|
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Based on the clinical features and laboratory findings, a diagnosis of Chanarin–Dorfman syndrome was made. A diet rich in medium-chain triglycerides and low in other fats was advised. Emollients and keratolytics were prescribed. Marginal improvement was noted at 2 months of follow-up.
| Discussion|| |
Chanarin–Dorfman syndrome is a rare form of ichthyosis. The first case was described in 1974 by Dorfman. It is also known as neutral lipid storage disorder with ichthyosis or ichthyosiform erythroderma along with leukocyte vacuolization.
It is an autosomal recessive disorder occurring due to mutation in the CGI-58/abhydrolase domain-containing 5 (ABHD5) gene. The product of this gene is a cofactor for adipose triglyceride lipase, also known as ABHD5. ABHD5 enhances PNPLA1-catalyzed acyl ceramide production, which integrates into the cornified envelope of the skin. It is also responsible for triglyceride lipolysis. Its absence leads to intracellular accumulation of triacylglycerol in various organs, including the skin, muscles, liver, and brain, resulting in a plethora of clinical manifestations.
Skin involvement occurs in the form of severe ichthyosis, progressively worsening with age. The most frequently involved organ is liver, manifesting as nontender hepatomegaly, often reaching massive proportions. Patients may survive into adulthood with the development of liver cirrhosis. Other features include myopathy, sensorineural deafness, short stature, coarse facies, and mental retardation. Ocular involvement may occur in the form of cataract, nystagmus, strabismus, and myopia. Splenomegaly, microcephaly, and intestinal involvement have been reported occasionally.
The characteristic finding of Jordan's anomaly on the peripheral smear is diagnostic of this disease., However, cases of Chanarin–Dorfman syndrome without Jordan's anomaly have also been reported. Here, electron microscopy of the skin can be used to demonstrate intracytoplasmic, extralysosomal, nonmembrane-bound neutral lipid vacuoles.
Special stains such as oil red can be used to demonstrate intracellular fat on histopathology. Other tissues showing lipid deposition include liver, muscle, ears, eyes, brain, intestine, and kidneys. Hence, liver biopsy, muscle biopsy, and renal biopsy may be done. Genetic studies are confirmatory.
Treatment involves topical application of emollients for ichthyosis. Keratolytic agents may be used. Severe cases necessitate use of systemic retinoids. Although systemic retinoids are known to cause liver enzyme elevations, benefits of acitretin treatment have been reported in some cases, possibly due to induction of lipases in specific tissues., Hence, a careful assessment of individual cases is to be done.
The cornerstone of management is dietary modification aimed to reduce the dietary intake of fats and restricted intake of medium- and low-chain triglycerides. This decreases serum triglyceride level and ensures relatively less accumulation of intracellular triacylglycerols. Liver transplant remains the mainstay of therapy in advanced cases and may be life-saving.
Chanarin–Dorfman syndrome is one of the rarer causes of collodion baby clinically resembling other causes of congenital, nonbullous ichthyosiform erythroderma. However, Jordan's anomaly is a diagnostic feature. Hence, a peripheral blood smear examination must be undertaken in all cases of congenital ichthyosiform erythroderma, especially those presenting with hepatomegaly.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]