A Two-Year-Old Child with Bilateral Symmetrical Papulosquamous Lesions

A two-year-old girl, born at full term by vaginal delivery to parents with nonconsanguineous marriage, was presented with a complaint of erythematous scaly plaques over the abdomen since the age of two months which gradually progressed to face and extremities in a symmetrical pattern. The lesions started to develop after weaning at the age of two months. The patient was evaluated by gastrologists before for iron deficiency anaemia and transaminitis. She had no developmental delay or physical abnormalities. There was no history of bullae or erosions at any point in time. Cutaneous examination revealed the presence of well-defined, erythematous, symmetrical fine scaly plaques over the trunk, extremities, and face [Figures 1 and 2]. The palms, soles, hair, teeth, mucosa, and nails appeared normal. Skin biopsy [Figure 3] after proper guardian consent revealed orthokeratosis, parakeratosis, focal spongiosis and papillomatosis of the epidermis, and mild to moderate perivascular lymphoplasmacytic infiltrate in the dermis. Her investigations are summarised in Table 1.Figure 1: Symmetric papulosquamous lesions on lower limbsFigure 2: Symmetric papulosquamous lesions with fine scaling on abdomen and upper limbFigure 3: Orthokeratosis, parakeratosis, focal spongiosis, papillomatosis, and superficial perivascular mild infiltrateTable 1: Investigations done in our caseWhat is your diagnosis? Diagnosis: Chanarin–Dorfman syndrome. Discussion Chanarin–Dorfman syndrome (CDS) is an extremely rare, multisystemic, autosomal recessive, neutral lipid storage disease (NLSD). It was first observed by Jordan later, Dorfman and Chanarin reported it for the first time as a NLSD. The syndrome is caused by the mutation of the abhydrolase domain containing 5 (ABHD5)[1,2] (formerly CGI-58) gene. This gene produces a protein involved in fat metabolism, called CGI-58, which is a cofactor that helps the activity of the main enzyme adipose triacylglycerol lipase (ATGL).[3] The function of this enzyme is to break down a type of fat, called triacylglycerol (TAG). This process is disturbed when either the enzyme or the helper protein does not work properly. When the fat (triacylglycerol) cannot be broken down, it accumulates in various parts of the body, especially in the skin, liver, and white blood cells as lipid droplets, and causes different symptoms. The effect on the skin is an abnormal permeability, which leads to a characteristic rash and intense itching. In the liver, the lipid droplet accumulation leads to fatty change called 'steatosis', which can eventually progress to cirrhosis and liver failure. The most prominent features are nonbullous congenital ichthyosiform erythroderma and liver steatosis; however, other patterns, such as nonspecific ichthyotic patterns and erythrokeratoderma variabilis-like[4] patterns, have occasionally been reported. Extracutaneous involvement in CDS ranges from no clinical symptoms to multisystemic involvement. Involvement of the liver (64%), spleen (24%), muscle (61%), and CNS (30%) is frequent. Most common blood tests, including those of serum lipids, are normal, but muscular and hepatic enzymes are often found to be moderately elevated. Cardiac, ocular and intestinal anomalies, hearing loss, short stature, and microcephaly are other possible manifestations. In our case, the patient had mild hepatomegaly with persistently raised transaminase levels with all other systems being uninvolved. A low serum zinc level in this patient may be an incidental finding exacerbating the symptoms, highlighting the importance of addressing potential nutritional deficiencies. Very few cases are reported with erythrokeratoderma variabilis progressiva (EKVP)-like lesions in CDS. An easy screening tool in the form of peripheral blood smear or buffy coat preparation that reveals granulocytes with lipid-laden vacuoles (Jordan anomaly)[5] and liver enzymes can be done in patients with EKVP-like lesions. In our case, as it was not suspected, Jordan anomaly was not looked for in previous reports. Sudan red stain and ultrastructural examination were not done because of unavailability at our centre. The histopathological features observed in Chanarin–Dorfman syndrome often exhibit nonspecific characteristics. However, specific presentations, such as erythrokeratoderma variabilis, typically show orthohyperkeratosis, variable parakeratosis, irregular acanthosis, and papillomatosis. Conversely, nonbullous ichthyosiform erythroderma shows marked hyperkeratosis and mild acanthosis. However, genetic analysis using whole-exome gene sequencing revealed a homozygous missense mutation in exon 6 of the ABHD5 gene (chr3:g. 43717790C>T) with uncertain significance that results in the amino acid substitution of phenylalanine for serine at codon 298 (p.Ser298Phe; ENST00 000644371.2). As the patient was then lost to follow up, further confirmation with Sanger sequencing could not be obtained. A multidisciplinary approach is required for the management. Diet is especially one of the most important components of therapy. The recent observation is that a diet poor in long-chain fatty acids and enriched with medium-chain fatty acids improves skin and liver manifestations. So, an early initiation of such a diet might prevent systemic disturbances and improve skin alterations. 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. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.