A novel mutation in the sterol 27-hydroxylase gene of a woman with autosomal recessive cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX) (OMIM 213700; ORPHA 909) [1,2] is an autosomal recessive sterol storage disease caused by mutations of the sterol 27-hydroxylase-gene (CYP 27). The CYP27A1 gene is located on chromosome 2q33-qter and consists of 9 exons. Sterol 27-hydroxylase is a mitochondrial cytochrome P 450 enzyme that catalyzes the initial steps in the oxidation of side chain of sterol intermediates in the pathway leading to the formation of bile acids in the liver [3-5]. In CTX patients the ability to convert cholesterol to bile acids is impaired and the incomplete oxidation of the cholesterol side chain leads to the accumulation of cholesterol and abnormal tetra-and penta-hydroxylated bile alcohols in tendons, lenses, the central nervous system and lungs. Children with CTX will often have diarrhea of unknown cause and develop juvenile cataracts and tendon xanthomas [6]. Premature atherosclerosis has also been observed. The characteristic neurological features often leading to diagnosis in the second or third decade of life are pyramidal tract signs, cerebellar syndrome, peripheral neuropathy, epileptic seizures, speech- and swallowing-disorders.Currently, about 50 mutations of the CYP27A1 gene are known [7-11], mainly affecting the adrenodoxin-binding and heme binding-sites of the sterol 27-hydroxylase. Here we describe clinical findings, biochemical parameters and a novel mutation of the CYP27A1 gene in a woman with CTX.The patient, a 35 year-old german female, complained of a progressive disturbance of gait over the last 3 years. She had a history of recurrent diarrhea and bronchitis, growth retardation, a mild retardation of psychomotor development in infancy and bilateral juvenile cataracts. She attended a school for mentally and physically handicapped children. At age 24 a normal pregnancy and delivered an apparently healthy child. Another child died four days after birth. There was no information about the proband's father so that consanguinity or cl