Cerebrotendinous xanthomatosis

Diagnosis and Testing

How do I get tested for cerebrotendinous xanthomatosis?

A doctor may suspect a diagnosis of cerebrotendinous xanthomatosis because of the symptoms a person has. An infant with chronic diarrhea that doesn't respond to treatment or cataracts in young children, or cholestatic liver disease in infants without an apparent cause. Unexplained neurological disease in adolescents or adults can also be a sign. Even if a diagnosis isn't suspected, these symptoms might lead to a patient being referred to a specialist. A referral to local genetics clinic or a genetic metabolic specialist may also be made. Unfortunately, the symptoms of this disorder are so varied that a delay in diagnosis of many years is common. The mean age of diagnosis is around 35-37 years of age.

A suspected diagnosis should lead to biochemical testing. This type of testing measures the levels of certain chemicals in blood and urine samples. This includes measuring cholestanol concentration in the blood plasma or bile alcohol levels in the urine or blood plasma. These chemicals are found in high concentrations in people with cerebrotendinous xanthomatosis. A diagnosis can be confirmed by molecular genetic testing. This type of testing looks for the gene changes that cause the disorder. Both biochemical and molecular genetic testing must be done at specialized laboratories that have experience with cerebrotendinous xanthomatosis and related disorders.

Physicians have created a suspicion index, which assigns weighted scores indicators of cerebrotendinous xanthomatosis such as family history characteristics and common systemic and neurological features of the disorder. The indicators are classified as very strong (score 100), strong (50) or moderate (25).

A genetics professional nearby can discuss information and testing for CTX. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

References
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More Diagnosis and Testing Content

Is there newborn testing for cerebrotendinous xanthomatosis?

Is there more than one test for cerebrotendinous xanthomatosis?

Who else in my family should I test for cerebrotendinous xanthomatosis?

What tests support a diagnosis of cerebrotendinous xanthomatosis?

Can cerebrotendinous xanthomatosis be detected before birth?

Is there newborn testing for cerebrotendinous xanthomatosis?

Cerebrotendinous xanthomatosis is not one of the disorders that is routinely screened for in newborns. Newborn screening is a way for doctors to test newborn babies for certain inherited disorders. During newborn screening, a tiny sample of blood, called a dried blood spot, is taken from a newborn. This blood sample is run through a machine like a tandem mass spectrometer. This machine can separate and measure certain substances based upon their molecular weight.

Researchers have developed a test that can detect cerebrotendinous xanthomatosis by studying a dried blood spot. The test would detect high levels of a specific chemical, called 7α,12α-dihydroxy-4-cholesten-3-one or 7α12αC4. This chemical is a bile acid precursor. A precursor is a substance from which another substance is formed, usually through a chemical (metabolic) reaction. This test is still in the developmental stage. A potential newborn screening test is important because cerebrotendinous xanthomatosis can be treated and certain symptoms may be prevented if people are diagnosed and treatment is begun early enough.

More information about newborn screening is available from the National Newborn Screening & Global Resources Center in Austin, Texas or the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia.

References
  • Bleyle S, Huidekoper H, Vaz FM, et al. Update on newborn dried bloodspot testing for cerebrotendinous xanthomatosis: An available high-throughput liquid-chromatography tandem mass spectrometry method. Mot Genet Metab Rep. 2016;7:11-15.
  • DeBarber AE, Luo J, Star-Weinstock M, et al. A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns. J Lipid Res. 2014;55(1):146-54.
Is there more than one test for cerebrotendinous xanthomatosis?

Cerebrotendinous xanthomatosis can be diagnosed by blood or urine tests. Doctors will test blood samples for cholestenol concentration. Blood samples or plasma (the fluid part of blood) may have high levels of cholesterol as well. The plasma will also contain high levels of bile acid precursors. A precursor is a substance from which another substance is formed, usually through a chemical (metabolic) reaction. The concentration of bile alcohols will be high in urine and plasma samples as well as in the bile. These blood and urine tests are best done at a laboratory that is experienced in performing such tests.

Molecular genetic testing can be used to confirm a diagnosis of cerebrotendinous xanthomatosis. These tests involve studying the CYP27A1 gene for changes that cause the disorder. This can include targeted mutation analysis, where specific, known changes in a gene are looked for; sequence analysis, where a part or sequence of DNA within a gene is examined; or deletion/duplication analysis, where missing or extra regions of DNA are looked for within a specific gene. Molecular genetic testing must be done at specialized laboratories.

A genetics professional nearby can discuss information and testing for CTX. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

References
  • Federico A, Dotti MT, Gahl W. Cerebrotendinous Xanthomatosis. GeneReviews website. http://www.ncbi.nlm.nih.gov/books/NBK1409/ Updated August 1, 2013. Accessed April 10, 2016.
  • Berginer VM, Salen G, Patel SB. Cerebrotendinous Xanthomatosis. In: Rosenberg RN, Pascual JM, eds. Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease. 5th edition. Philadelphia, PA:Elsevier, Inc.;2015.
Who else in my family should I test for cerebrotendinous xanthomatosis?

In a family with cerebrotendinous xanthomatosis, other testing can be done to see whether at-risk family members are carriers for the disorder. However, the specific gene changes in that family must be known. If known, all siblings of an affected child can be tested to see whether they have the disorder or whether they are carriers. A newborn child in such a family must be tested either through a test that looks for a gene change (if known for that family) or tests that can measure certain chemical levels in the body. A genetic counselor or physician with experience in cerebrotendinous xanthomatosis can provide advice about how a diagnosis can impact other family members.

Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

References
What tests support a diagnosis of cerebrotendinous xanthomatosis?

People with cerebrotendinous xanthomatosis will undergo neurological examination including specialized x-ray techniques, electroencephalography, and nerve conduction studies. These tests may be done after a diagnosis is made to assess how far along the disease is, or before a diagnosis is known when doctors are trying to figure out what is wrong with a person. These tests may reveal changes that are not specific to cerebrotendinous xanthomatosis, but can be seen in many different neurological disorders.

Computed tomography, or a CAT scan, and magnetic resonance imaging, or an MRI, are specialized imaging techniques that allow doctors to view structures in the body. Doctors use these tests because they can reveal areas in the brain that are damaged in cerebrotendinous xanthomatosis. For example, some areas of the brain may appear lighter in color than the surrounding tissue. This is called hyperintensity and indicates damage to that area of the brain. In some people damage can be seen in the white matter or in a cluster of nerve cells called dentate nuclei.

Individuals often have an abnormal electroencephalography or EEG. This is a painless test that records the electrical activity in the brain. Electrodes are placed on the scalp and record the electrical waves during periods of activity. In some people with cerebrotendinous xanthomatosis the electrical waves may be slow with occasional bursts of activity.

A nerve conduction study measures how fast nerve impulses pass through a nerve. If this test shows the nerve impulses traveling slowly, then damage to the nerves is present.

References
  • Berginer VM, Salen G, Patel SB. Cerebrotendinous Xanthomatosis. In: Rosenberg RN, Pascual JM, eds. Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease. 5th edition. Philadelphia, PA:Elsevier, Inc.;2015.
  • Nie S, Chen G, Cao X, Zhang Y. Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. 2014 Nov 26;9:179.
  • Cerebrotendinous Xanthomatosis. National Organization for Rare Disorders website. http://rarediseases.org/rare-diseases/cerebrotendinous-xanthomatosis/. Updated 2014. Accessed April 10, 2016.
Can cerebrotendinous xanthomatosis be detected before birth?

Some parents may choose to have their child tested for cerebrotendinous xanthomatosis before the child is born. This is known as prenatal diagnosis. This is only possible in families with a child who already has a diagnosis of cerebrotendinous xanthomatosis and in whom the disease-causing gene change is known. A sample of tissue for testing can be taken from the placenta. This test is called chorionic villus sampling. Another test is called amniocentesis, which involves taking a sample of the amniotic fluid that surrounds and protects a developing fetus. Cells known as amniocytes are taken from the fluid and studied. Prenatal diagnosis must be done at a research or clinical laboratory.

Genetic counselors can help you learn more about prenatal testing. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

References

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