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Clinical report: A patient with a late diagnosis of cerebrotendinous xanthomatosis and a response to treatment
Author(s) -
Alhariri Ahmad,
Hamilton Katherine,
Oza Vikash,
Cordoro Kelly,
Sobreira Nara L.,
Malloy Mary,
Slavotinek Anne
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38314
Subject(s) - cerebrotendinous xanthomatosis , cholestanol , chenodeoxycholic acid , cyp27a1 , xanthoma , nonsense mutation , medicine , compound heterozygosity , gastroenterology , endocrinology , bile acid , pediatrics , allele , mutation , missense mutation , biology , genetics , cholesterol , gene , sterol
Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive, inborn error of bile acid metabolism characterized by diarrhea in infancy, juvenile cataracts in childhood, tendon xanthomas developing in the second to third decades of life, and progressive neurologic dysfunction in adulthood. The condition is caused by mutations in the CYP27A1 gene that result in decreased production of chenodeoxycholic acid (CDCA) and elevated levels of cholestanol and bile alcohols. We present a 36‐year‐old male of Han ethnicity who developed xanthomas of his Achilles tendons and suffered neurocognitive declines and gait deterioration in his second decade. The diagnosis of CTX was confirmed by marked elevation of the serum cholestanol level. Sequencing of CYP27A1 showed a paternally inherited splice mutation, c.446 + 1G>T, and a maternally inherited nonsense mutation, c.808C>T, predicting p.(Arg270*). Despite the advanced disease in this patient, treatment with CDCA reduced the xanthoma size and improved his cognition and strength, and the patient made significant gains in his ambulation and coordination. We report this case to illustrate the potential benefits of therapy in patients with CTX who have advanced disease at the time of diagnosis.