Chanarin-Dorfman Syndrome with Absent Jordan's Anomaly.

Sir,

Chanarin-Dorfman syndrome (CDS) is a rare inherited disorder characterized by congenital ichthyosis, nonbullous ichthyosiform erythroderma, myopathy, and hepatic involvement with deposition of neutral lipids in skin, muscle, liver, central nervous system, and granulocytes. Variable skin and systemic involvement makes diagnosis difficult in some cases wherein an easy screening tool in the form of peripheral blood smear or buffy coat preparation reveals granulocytes with lipid-laden vacuoles (Jordan's anomaly).[1]

An 8-year-old boy, born of a nonconsanguineous marriage with an uneventful antenatal and perinatal period, was brought to dermatology outpatient with a history of a partial membrane encasing the child at birth which gave way to generalized dryness of skin, scaling, and erythema over the next 4 weeks worsening for a few months and thereafter remitting except for winter exacerbations. Four months before presentation, he developed difficulty in getting up from sitting position and climbing of stairs with progressive increase in the bulk of calves.

There was no history of difficulty in feeding, icterus, dark-colored urine or clay-colored stools, seizure, loss of weight and appetite, difficulty in swallowing, photosensitivity, ocular complaints, hearing impairment, or history suggestive of mental retardation. No other family member had similar illness.

Examination revealed generalized scaling on a background of erythema with accentuation at flexures and palmoplantar keratoderma [Figure 1]. Abdomen was distended with firm, nontender hepatomegaly; calf muscle bulk was increased bilaterally, with reduced tone and power of the proximal muscle of the thigh; plantar reflex was decreased, whereas other deep tendon reflexes were normal. Gower's sign was positive [Figure 2]. Ocular examination was normal. His height and weight were normal for his age.

Figure 1

Diffuse fine scaling on a background of erythema; calf muscle hypertrophy (inset)

Figure 2

Proximal muscle weakness evident with a positive Gower's sign

Investigations revealed normal hemogram, renal function tests, blood sugar levels, serum electrolytes, and lipid profile. Liver and muscle enzymes were elevated with alanine transaminase 390 IU/L, aspartate transaminase 442 IU/L, alkaline phosphatase 298 IU/L, creatinine kinase 1409 IU/L, creatinine kinase MB: 426.8 IU/L, and lactate dehydrogenase 785 IU/L. Peripheral blood smear done repeatedly including from buffy coat preparations, and bone marrow smears revealed no abnormality with the absence of lipid-laden cells on light microscopy.[2] Electromyographic study showed early recruitment with complete interphase pattern suggestive of myopathic pattern. Abdominal ultrasonography showed mild hepatomegaly with mild fatty infiltration. Skin biopsy revealed hyperkeratosis, prominent granular layer, and mild lymphocytic infiltration. Electron microscopy of the skin revealed intracytoplasmic, extralysosomal, nonmembrane-bound neutral lipid vacuoles [Figure 3]. Screening of parents and elder sibs revealed no abnormality.

Figure 3

Photomicrograph showing hyperkeratosis, prominent granular layer, and mild lymphocytic infiltration (H and E ×10) (left); transmission electron microscopy of the skin preparation fixed in glutaraldehyde and postfixed in osmium tetroxide showing lipid droplets at the dermoepidermal junction in the basal cells, transmission electron micrograph (×6000)

The child was placed on topical emolients and acitretin 10 mg daily, along with regular physiotherapy and followed up thereafter. The scaling and erythema reduced, muscle weakness is static. Liver enzymes after 3 months showed reduction, alanine transaminase 220 IU/L, aspartate transaminase 240 IU/L, alkaline phosphatase 202 IU/L, and creatinine kinase 1298 IU/L [Figure 4].

Figure 4

Pretreatment (left) and posttreatment (right) images of the face, palms, and soles at the end of 3-month follow-up

CDS described initially by Dorfman et al.[3] is an autosomal recessive inborn error of metabolism characterized by cytoplasmic accumulation of neutral lipids in cells of skin, muscles, liver, gastrointestinal tract, central nervous system, and various blood and bone marrow cell lines along with nonbullous congenital ichthyosiform erythroderma. It is caused by a mutation in the ABHD5 gene on chromosome 3p21 which acts as a cofactor for adipose triglyceride lipase involved in the catabolism of fat.[24] Ichthyosis and demonstration of these lipid droplets are consistent features while demonstration of lipid droplets in blood cells (Jordan's anomaly) has served as a useful screening tool in CDS and other neutral lipid disorders. Serum lipids remain normal while muscle and hepatic enzymes are usually elevated.

Clinically these patients present as congenital ichthyosiform non-bullous erythroderma, along with variable multiorgan involvement such as growth retardation, ocular changes as cataract, nystagmus and retinal changes, neurological abnormalities with areflexia, hypotonia, proximal muscle weakness, ptosis, mental retardation and variable cranial nerve involvement. A protuberant abdomen with hepatic steatosis, portal hypertension, myopathy, and psychiatric disorders may also be present in some cases.

Management remains symptomatic. Restricted carbohydrates and medium-chain triglycerides in diet may be helpful if instituted early but difficult to enforce for long duration.[5] Acitretin shows a good response even in the presence of elevated liver enzymes.[6]

Our patient, an 8-year-old male, was diagnosed as a case of CDS based on history of a partial collodion, congenital nonbullous ichthyosiform erythroderma, with hepatic steatosis proximal myopathy, partial areflexia of plantar reflexes, and demonstration of lipid droplets on electron microscopy. Jordan's anomaly a hitherto described screening test for this condition observed on light microscopy of peripheral cells of probands as well as heterozygous carriers[7] was negative in our case; however it is possible electron microscopy of peripheral cells may have revealed lipid droplets.[8] Electron microscopy of peripheral blood cells was not done. Parents were unwilling for mutation analysis. He showed a good response on acitretin and has been placed on follow-up.

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Conflicts of interest

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