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CTX - Cerebrotendinous Xanthomatosis

CTX is one of the rare metabolic diseases. Sometimes the name Cerebral Cholesterinosis is used.

When we dissect the name we discover that this disease has to do with brains, tendons and with fat storage in tissues.

- Cerebro: brain
- Tendinum: tendon, tendinous refers to the tendons in the body
- Xanthomathosis: fat deposits; accumulation of cholesterol and cholestanol in the tissues of patients.

 

In the case of CTX, the enzyme that converts cholesterol into bile acids is missing. Bile acids are necessary for the absorption of fats. These fats are necessary for the body and are absorbed in the intestines. A certain protein (enzyme; sterol 27-hydroxylase) is not or hardly produced, so that chenodeoxycholic acid (CDZ) is also not properly produced. This leads to the precipitation, accumulation of fats in the brain, eye lenses and tendons with the symptoms listed below.

 

Symptoms

The disease can show signs in a child after birth, such as jaundice and chronic diarrhea. Children often don't get all the symptoms. About half of them develop diarrhea. Often it also turns out in older patients afterwards that diarrhea and poorer vision were the first symptoms of the disease. The disease is not always recognized. CTX is slowly progressive.

 

Complaints that may occur

  • Chronic diarrhea,
  • Impaired sight
  • Cataract in both eyes (juvenile cataract),
  • Optic nerve gets smaller in some of the people with CTX (optic atrophy),
  • Fat swelling in the tendons (does not always occur),
  • Fat deposits in the skin (xanthelesmata); small yellowish fat lumps, for example, on the eyelids,
  • Learning difficulties (sometimes as early as primary school age, more often as from secondary school age),
  • Balance problems (from puberty), falling, wide gait (ataxia),
  • Movement disorders (parkinsonism),
  • Gradually increasing stiff muscles with high muscle tone (spasticity) (dystonia),
  • Muscle weakness starting in feet and lower legs, later in hands, legs and arms,
  • Altered sensation, feeling less well in hands and feet,
  • Behavioral changes, gloominess, more irritable,
  • Psychoses, hallucinations,
  • Overstimulation
  • Dementia-like complaints and FTD,
  • Epilepsy
  • Arteriosclerosis,
  • Heart problems, chest pain, decreased pumping power causing fluid retention and fatigue,
  • Osteoporosis.

DNA research

When there is someone with CTX in a family, DNA research is done. By this it may be that CTX is discovered in brothers and sisters even before they get sick. Early treatment can have a lot of effect.
An error in the hereditary material can be discovered on the 2nd chromosome (2q35) at the CYP27A1 gene.

 

Autosomal recessive hereditary

In autosomal hereditary diseases, both parents often bear the error in the genetic material. Children of these parents have a 25% chance of getting this disease. 50% do not get sick but carry the gene. The remaining 25% do not get sick and are not carriers.

 

Treatment

For an explanation of the treatment, we refer to

the website about CTX.

 

Sources

- Cali JJ, Hsieh CL, Francke U, Russell DW: Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem. 1991, 266: 7779-7783.PubMed

- Chales G, Coiffier G, Guggenbuhl P: Miscellaneous non-inflammatory musculoskeletal conditions. Rare thesaurismosis and xanthomatosis. Best Pract Res Clin Rheumatol. 2011, 25: 683-701.PubMed

 

- Gallus GN, Dotti MT, Federico A: Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene. Neurol Sci. 2006, 27: 143-149.PubMed

 

- Guyant-Marechal L, Verrips A, Girard C, Wevers RA, Zijlstra F, Sistermans E, Vera P, Campion D, Hannequin D: Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype. Am J Med Genet A. 2005, 139A: 114-117.PubMed

- van Heijst AFJ, Verrips A, Wevers RA, Cruysberg JRM, Renier WO, Tolboom JJM: Treatment and follow-up of children with cerebrotendinous xanthomatosis. Eur J Pediatr. 1998, 157: 313-316.PubMed

 

- Lagarde J, Sedel F, Degos B: Blepharospasm as a new feature of cerebrotendinous xanthomatosis. Parkinsonism Relat Disord. 2013, 19: 764-765.PubMed

 

- Yahalom G, Tsabari R, Molshatzki N, Ephraty L, Cohen H, Hassin-Baer S: Neurological outcome in cerebrotendinous xanthomatosis treated with chenodeoxycholic acid: early versus late diagnosis. Clin Neuropharmacol. 2013, 36: 78-83.PubMed