A 24-year-old male presents with several years of progressive bilateral growth near his achilles tendons. He complains of distal leg discomfort after working a long day in the grocery store; otherwise, this is not bothersome, except for the appearance.
His past medical history includes attention deficit disorder, irritable bowel syndrome with diarrhea since childhood, and bilateral cataracts requiring surgery at the age of 20. His diarrhea is somewhat improved with a gluten-free diet. An older sister also has diarrhea and cataracts without Achilles growth. His medications include omeprazole 20 mg daily. He denies any over-the-counter supplements or vitamins and denies tobacco, alcohol, or illicit drug use. A review of systems is remarkable for decreased concentration.
On exam, he is 67 inches tall and weighs 48 kg (BMI 16.5 kg/m2), his blood pressure is 125/78 mmHg, his heart rate is 58 bpm, and his respirations are 16/minute. He has a prominent forehead and clear lungs. He has normal S1 and S2 without murmurs, rubs, or gallops. There are no masses except for his Achilles and ankles, which are shown in Figures 1 and 2.
Figure 1
Figure 2
Which of the following is the best test to confirm the diagnosis?
Show Answer
The correct answer is: D. Serum cholestanol.
Elevated serum cholestanol levels will confirm the diagnosis of cerebrotendinous xanthomatosis (CTX). This patient's level is 35.64 mcg/ml (normal range 0.8-3.7 mcg/ml). CTX is a rare, autosomal recessive disorder of the CYP27A1 gene that results in diminished bile acid synthesis of sterol-27 hydroxylase.1 This deficiency results in elevated levels of cholesterol and cholestanol and subsequent deposition into various tissues. Elevated cholestanol and cholesterol deposits typically lead to infantile or childhood diarrhea, cataracts, and xanthomas in young adulthood, as well as premature atherosclerosis. Achilles xanthomas are the most common, but other xanthomas include extensor elbow, hand, neck, or patellar. A later stage of the disease results in cerebral deposits leading to paranoia, hallucinations, extrapyramidal symptoms, and various other neurologic manifestations.
CTX is treatable with bile acid replacement therapy in the form of chenodeoxycholic acid. Additional therapy with statins, LDL aphersis, or liver transplant has not shown significant benefit and limited data support their use.2
An MRI of the Achilles will probably show increased cholesterol deposits but will not provide a definitive diagnosis. Answer option B (lipid panel) is incorrect because most patients with CTX have normal or just slightly increased serum cholesterol levels. Answer option C (cardiac MRI) is not warranted with this presentation and answer option E (genetic testing for LDL receptor) would not be helpful.
References
Moghadasian MH, Salen G, Frohlich JJ, et al. Cerebrotendinous xanthomatosis a rare disease with diverse manifestations. Arch Neurol 2002;59:527-9.
Federico A, Dotti MT. Cerebrotendinous xanthomatosis: clinical manifestations, diagnostic criteria, pathogenesis, and therapy. J Child Neurol 2003;18:633-8.
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