*A unique case of xanthoma tendinosum

Abstract

Background/Synopsis

Tendon xanthomas are a rare physical finding most commonly associated with familial hypercholesterolemia (FH), but can be associated with other genetic diagnoses.

Objective/Purpose

We describe a patient with prominent xanthomas and the diagnostic approach.

Methods

Electronic medical records of the patient were reviewed.

Results

A 54-year-old man, non-smoker, of Greek ethnicity presented with large xanthomas on his Achilles tendons, knees, and metacarpal joints (Figure 1). He first noticed xanthomas in his thirties and was started on rosuvastatin due to paternal family history of early heart disease. The xanthomas progressed despite statin therapy. He did not participate in sports as a child due to associated fatigue. Besides mild memory issues, he had no complaints.

Although FH was the leading diagnosis in the differential for xanthomas, his untreated LDL-C was never higher than 120 mg/dL and was 58mg/dL on rosuvastatin 20mg daily. His lipoprotein(a) (Lp(a)) was in normal range and Lp(a) elevation is not known to be associated with xanthomas. Based on exertional dyspnea with aerobic exercise, a coronary CT angiography was performed showing mild non-obstructive coronary artery disease, and his echocardiogram was normal.

Phytosterolemia was excluded by normal plasma sitosterol concentration and absence of pathogenic variants in ABCG5 or ABCG8. Cerebrotendinous xanthomatosis (CTX) was also considered, however, he had no typical symptoms, normal cholestanol levels, a normal neurological evaluation and normal MRI of his brain, making CTX less likely. A 25 gene genetic panel revealed pathogenic homozygous variants in the CYP27A1 gene. Subsequent levels of plasma 7-alpha, 12-alpha-dihydroxy-4-cholesten-3-one and urine bile alcohols were consistent with CTX. He was started on chenodeoxycholic acid and aspirin in the setting of coronary disease.

Conclusions

CTX is a rare, recessive genetic lipid storage disorder. Mutations in the CYP27A1 gene cause sterol 27-hydroxylase deficiency which blocks bile acid synthesis and leads to accumulation of bile acid metabolites in tissues. Cholestanol is commonly elevated, but not always. CTX can affect many organ systems and diagnosis is challenging due to varied phenotypes. Early onset cataracts, diarrhea, and progressive neurological decline are common. Some patients develop atherosclerosis. Early diagnosis is key to preventing complications. To date, there are few known cases of CTX with normal cholestanol as seen in our patient, but almost all have large xanthomas. Screening for CTX in patients with xanthomas is recommended, with a normal cholestanol level being insufficient to exclude the diagnosis. Further studies are needed to better understand phenotypic variations in patients with genetically confirmed CTX.