Cerebrotendinous Xanthomatosis (CTX)
https://cerebellumandataxias.biomedcentral.com/articles/10.1186/s40673-021-00128-2
Cerebrotendinous Xanthomatosis (CTX) is a rare condition caused by mutations in the gene CYP27A1. This gene contains instructions for making the protein CYP27A1, which is required for bile acid production. Bile acids have numerous functions in the body, but are principally needed for aiding in the digestion of dietary fats and helping to eliminate cholesterol from the body. When CYP27A1 does not function properly, a chemical known as ‘cholestanol’ accumulates and causes damage to various bodily tissues, including the eyes, part of the brain and tendons. CTX is a serious disorder. However, it is treatable, with best results achieved when the condition is identified as early as possible. This is complicated by the fact that CTX can manifest in diverse ways, with even affected identical twins experiencing different symptoms. Typical symptoms of CTX include: infantile-onset diarrhoea, childhood and juvenile onset cataracts, tendon xanthomata (nodules which form under the skin over tendons, usually the Achilles tendon and in the hands and feet), and either childhood or adult-onset neurological problems. These symptoms may occur in CTX patients to varying degrees and in varying combinations. This article describes the experience of four patients affected by CTX in detail, including both their current and historical symptoms, and the treatments they have received/are receiving. All four patients had extremely different experiences of CTX, and between them had a median age of diagnosis of 39 years, despite some having had symptoms since childhood. Typically, CTX is diagnosed based on the presence of early-onset cataracts, tendon xanthomata and progressive ataxia (uncoordinated movement and speech). However, in the patients described in this paper, this ‘triad’ of symptoms was only present in one out of the four individuals. Unlike many complex conditions affecting the central nervous system, CTX is treatable, with administration of chenodeoxycholic acid (CDCA) being able to either reverse, stabilise or slow the progression the of the disease. Based on the descriptions of the first symptoms reported by the patients described in this paper, the authors conclude that when considering a diagnosis, spastic paraparesis (partial paralysis of the lower limbs), early-onset cataracts, and behavioural/cognitive problems more typically associated with autism spectrum disorders should be considered indicative of CTX, and cholestanol levels in both the blood and cerebrospinal fluid should tested as part of the diagnostic workup. Moving forward, the increased availability of genetic testing should also facilitate earlier diagnosis of CTX.