Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid disorder: phenotype Online Mendelian Inheritance in Man (OMIM)#213700, gene OMIM#606530 [
1]. It is caused by mutations in gene
CYP27A1 located on the chromosome 2q33-qter causing lack of enzyme mitochondrial sterol 27-hydroxylase [
1].
CYP27A1 plays a pivotal role in cholesterol side chain oxidation during the synthesis of chenodeoxycholic acid (CDCA) which is a bile acid [
2]. Therefore perturbations in
CYP27A1 gene result in reduced enzymatic activity causing impairment of cholesterol side chain oxidation finally culminating in excessive production and abnormal deposition of cholestanol in various tissues [
1,
2]. The classical triad of the syndrome consists of premature bilateral cataract, tendon xanthomas (predominantly involving tendo-Achilles) and various neurological abnormalities [
3]. A recent study by Appadurai
et al. [
2] stated that in the absence of epidemiological studies the disease is considered to be exceedingly rare but it is actually underreported. This group studied the Exome Aggregation Consortium (ExAC) cohort of 60,000 unrelated adults globally for the frequency of 57 reported pathogenic variants of
CYP27A1 along with 29 additional variants through bioinformatics; they estimated that the incidence of CTX ranged from 1:134,970 to 1:461,358 in Europe, 1:263,222 to 1:468,624 in Africa, 1:71,677 to 1:148,914 in the USA, 1:64,267 to 1:64,712 in East Asia, and 1:36,072 to 1:468,624 in South Asia [
2]. However, another recent study by Ragno
et al. stated that more than 300 cases have been reported so far with approximately 50 mutations with little correlation between genotype and phenotype [
4]. The mean age of onset of the symptoms is 19 years while the mean age at diagnosis is 35 years representing a lag of 16 years in the diagnosis [
5]. A recent study of 19 patients from 15 unrelated Italian families by Mignarri
et al. estimated the median age at diagnosis to be 32 years while the mean age was 32.5±10.4 years [
6]. Replacement therapy with CDCA delays or even reverses the progression of the disease [
3]; however, because there is a lag period between the onset of symptoms and the mean age of diagnosis [
1], early diagnosis is required to prevent devastating neurological sequelae and other complications such as premature atherosclerosis and osteoporosis. So a high index of suspicion should be kept in any patient encountered with the classical triad as illustrated in the present case report.