The following symptoms may occur in the course of CTX:
Cholestatic jaundice
Scientific reports indicate the occurrence of prolonged neonatal jaundice or cholestasis in newborns. It may therefore be the first symptom of a disease. Some retrospective studies have found that 8-16% of CTX patients had neonatal cholestatic jaundice.
Cataract
CTX patients present a high occurrence of idiopathic bilateral cataracts. Studies report its incidence of 75-80%. It is probably slightly more common in women. Cataracts can occur as early as in the first years of life. When considering most of the reports, it would seem that it is mainly diagnosed around 17. However, some develop cataracts only in late adulthood.
Tendon xanthomas
They manifest as enlargement and swelling of the tendon area, commonly of the Achilles tendon. However, they were also reported in patellar and elbow tendons. Xanthomas are found mostly after 20, being a rare finding in a pediatric population. In addition, this clinical manifestation is more likely to occur in a non-Asian population (89%) than in an Asian population (63%). It should also be noted that treatment with CDCA does not reduce the of already developed xanthomas in most cases. However, it inhibits their development and recurrence after surgical removal.
Diarrhea
Chronic diarrhea is the group of symptoms that may appear in the neonatal period. What’s more, it may also be the only symptom of the disease over a long period. Thus this clinical manifestation may be overlooked since a patient who has been used to this type of bowel movement for many years may not report it as disturbing. Less frequently, chronic diarrhea may not appear until adulthood. Information about chronic diarrhea incidence from 20-80% can be found. However, if a distinction is made between the non-Asian and Asian populations, the occurrence of the symptom can be assessed as 60-92% and 4-23%, respectively. Therefore, chronic diarrhea can be expected more often in patients of non-Asian origin. It is also a symptom that disappears quickly in many patients after starting treatment.
Cognitive impairment and psychiatric manifestations
Intellectual disability is one of the most common symptoms. It is a trait of CTX in about 70% of cases. Usually, it present along with developmental delay, but sometimes it can take the form of early dementia. Other manifestations that nearly half of the CTX patients face are behavioral and psychiatric symptoms. Reports have shown that the behavioral changes take mostly a form of aggressivity, irritability, and agitation. Such symptoms in pediatric cases led to attention deficit hyperactivity disorder or autism spectrum disorder diagnosis. Unfortunately, only with proper treatment of underlying disease could these behavioral changes be resolved. Other relatively common psychiatric symptoms are depression and anxiety. At last, in rare cases, psychotic symptoms in CTX were the cause of schizophrenia diagnosis.
Epilepsy
It is not a common manifestation in the disease course, with incidence reported 10-32% (rather near the lower spectrum). Usually, seizures start at a young age, but they can also occur in adulthood like other signs. Epilepsy in CTX patients is almost always accompanied by some degree of intellectual disability. Fortunately, in many known cases, CTX treatment also resolved seizures. Others responded quite well to classical anticonvulsants.
Ataxia, spastic paraparesis and speech impairment
Cerebellar symptoms in CTX patients can manifest as problems with coordination of movements and imbalance (called ataxia), speech impairment, or nystagmus (involuntary, rhythmic eye movements). In some cases, studies report an increase in muscle tone. All these symptoms are mostly leading to an unsteady gait. The incidence of those symptoms differs in studies, but mostly it is over 60%. Speech impairment can be found in 19-36% of CTX patients. Unfortunately, it can turn into problems with swallowing food with disease progression.
Polyneuropathy
About half of CTX patients will develop clinical or electrophysiological signs of polyneuropathy. Polyneuropathy is a set of symptoms associated with damage to many peripheral nerves. It primarily causes movement disorders and sensory disturbances.
Parkinsonism
Parkinsonism is a rare symptom in CTX patients, occurring in approximately 10%. Most commonly, symptoms of parkinsonism begin around the age of 40. Moreover, it is the first and only symptom of the underlying disease in some rare cases. Unfortunately, in cases of developed parkinsonism, CDCA treatment is seldom successful, and the L-dopa effectiveness is ambiguous.
Early osteoporosis and skeletal deformities
CTX patients may present with repeated fractures due to underlying early osteoporosis. Diagnosis is made by evaluation of bone mineral density. Osteoporosis incidence is around 23%, probably around 1.5 times more often in women. Another bone-related problem is skeletal deformities. The most prevalent is kyphosis (exaggerated, forward rounding of the back) and pes cavus (high arch in a foot). The latter is probably underdiagnosed, but it can be found in 40% of CTX patients (more commonly males).
CYP27A1