Cerebrotendinous xanthomatosis

A rare genetic disorder affecting cholesterol metabolism

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive genetic disorder characterized by the abnormal storage of cholesterol and cholestanol in various tissues, leading to a range of clinical manifestations. This condition is caused by mutations in the CYP27A1 gene, which encodes the enzyme sterol 27-hydroxylase, crucial for the normal metabolism of cholesterol.

Pathophysiology

CTX results from a deficiency in the enzyme sterol 27-hydroxylase, which is involved in the conversion of cholesterol to bile acids. The lack of this enzyme leads to the accumulation of cholestanol and cholesterol in various tissues, including the brain, tendons, and lungs. This accumulation causes the formation of xanthomas, which are cholesterol-rich deposits, and contributes to neurological and systemic symptoms.

Clinical Features

The clinical presentation of CTX is highly variable, but common features include:

• Neurological symptoms: Progressive cognitive decline, ataxia, seizures, and peripheral neuropathy.
• Tendon xanthomas: These are cholesterol deposits that typically occur in the Achilles tendon and other tendons.
• Juvenile cataracts: Early onset cataracts are often one of the first signs of the disease.
• Diarrhea: Chronic diarrhea is a common gastrointestinal symptom.
• Skeletal abnormalities: Osteoporosis and other bone-related issues may occur.

Diagnosis

Diagnosis of CTX is based on clinical evaluation, biochemical testing, and genetic analysis. Key diagnostic tests include:

• Biochemical tests: Elevated levels of cholestanol in the blood and cerebrospinal fluid.
• Genetic testing: Identification of mutations in the CYP27A1 gene.
• Imaging studies: MRI of the brain may show characteristic changes such as white matter abnormalities.

Treatment

The primary treatment for CTX is the administration of chenodeoxycholic acid (CDCA), which helps to normalize bile acid synthesis and reduce the accumulation of cholestanol. Early treatment can significantly improve symptoms and prevent disease progression. Additional treatments may include statins to lower cholesterol levels and supportive therapies for neurological symptoms.

Prognosis

With early diagnosis and treatment, individuals with CTX can have a significantly improved quality of life. However, if left untreated, the disease can lead to severe neurological impairment and reduced life expectancy.

Genetics

Autosomal recessive inheritance pattern

CTX is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the disease. Carriers, who have only one copy of the mutation, typically do not show symptoms.

Related pages

• Xanthoma
• Cholesterol metabolism
• Genetic disorders