Cerebrotendinous Xanthomatosis: An Early Diagnosis by Biochemical Tests

Abstract

To the Editor:A 17-y-old girl born to non-consanguineously married couple presented with bilateral, painless achillestendon swellings for 6 mo. She had normal birth and developmental history. She was operated for developmental cataract at 8 y of age. She did not have chronic diarrhea as a young child and had no history suggestive of nervous system involvement. Examination revealed a thinly built girl with firm, non-tender, fusiform swellings of both Achilles tendons, measuring 5 cm × 3 cm. She had pseudophakia (implanted intraocular lens) of both eyes. There was no evidence of pyramidal tract or cerebellar involvement. Based on her clinical presentation, the diagnosis of cerebrotendinous xanthomatosis (CTX) was suspected. Fine needle aspiration cytology of tendo-achilles swellings (Fig. 1a) showed giant cells with lipoid deposits within consistent with xanthomas. Differential diagnoses considered were hypercholesterolemia and sitosterolemia. Serum cholesterol was normal (144 mg%) which excluded hypercholesterolemia. Sitosterolemia is an inherited sterol storage disease characterized by tendon xanthomas but cataract is characteristically not a feature. Her serum cholestanol was elevated at 29.4 microgram/mL (normal 4.2±1.2 microgram/mL). Other cholesterol metabolites, 7-dehydro cholesterol, 8-dehydro cholesterol and 8(9)cholestenol were mildly elevated which confirmed the diagnosis. MRI brain was unremarkable except for altered Welchers angle – the angle between a line extending across the anterior cranial fossa to the tip to the dorsum sellae and another line along the posterior margin of the clivus. It was 120° (normal 113 to 115) (Fig. 1b). This has not been described as a feature of CTX in the literature. However, the classical MRI findings of the disease were demonstrated in two cases reported from the same region [1]. Plain X-ray of long bones, thyroid function tests, nerve conduction studies, ECG and echocardiogram were normal. Diagnosis was made before the onset of neurological manifestations. Van-Bogaert et al. first described the CTX phenotype in 1937 [2]. The varied manifestations of the disease are described in Table 1. CTX is a lipid storage disease. CYP27A1 is the only causative gene. The gene codes for the mitochondrial sterol 21-hydroxylase enzyme, which catalyzes oxidation of sterol intermediates during bile acid synthesis [3]. Loss of enzyme causes accumulation of cholestanol in many tissues. Deficiency of cholic acid and chenodeoxycholic acid also occurs; this alters permeability of blood–brain barrier and accumulation of excess cholestenol in brain causing neuronal cells apoptosis [4]. Treatment of choice is chenodeoxy-cholicacid. Early treatment prevents neurological abnormalities [5]. HMG-CoA-reductase-inhibitors alone or along with chenodeoxy-cholic-acid are also useful [6]. M. L. Kulkarni (*) Department of Pediatrics, JJM Medical College, Davanagere, Karnataka 577004, India e-mail: kulkarniml@yahoo.com