cerebrotendinous xanthomatosis

Overview of Cerebrotendinous Xanthomatosis (CTX)

Cerebrotendinous xanthomatosis is a rare genetic disorder characterized by the abnormal storage of fats (lipids) in various parts of the body. This condition leads to a wide range of potential abnormalities, making its presentation highly variable.

Common Signs and Symptoms

• Tendon Xanthomas: These are fatty deposits that can be found in tendons, particularly in the Achilles tendon.
• Neurological Dysfunction: CTX can lead to progressive neurologic problems such as seizures, cognitive impairment, difficulties with coordination and balance, and other symptoms like:
  • Intention tremor
  • Difficulty with fast hand movements
  • Nystagmus
  • Truncal ataxia
• Cataracts: Juvenile cataract is a common feature of CTX.
• Premature Atherosclerosis: The accumulation of lipids in the heart can lead to cardiovascular disease.
• Respiratory Failure: Lipid accumulation in the lungs can cause respiratory failure.

Other Possible Symptoms

• Infantile-onset Diarrhea
• Childhood-onset Cataract
• Progressive Neurological Problems: These can include seizures, cognitive impairment, and difficulties with coordination and balance.
• Hyperreflexia
• Hypothyroidism
• Increased Susceptibility to Fractures
• Intellectual Disability

Age of Symptom Onset

The average age of symptom onset for CTX patients is 19 years. Central nervous system symptoms and signs are frequently present and can serve as the first manifestation of the disease.

Diagnosis and Treatment

Diagnosis can be performed with a biochemical analysis of certain molecules in the blood and urine, or through molecular tests to confirm the diagnosis. Unfortunately, there is no cure for CTX, and treatment focuses on managing symptoms and preventing complications.

References:

• [1] Cerebrotendinous xanthomatosis is a disorder characterized by abnormal storage of fats (lipids) in many areas of the body.
• [3] For CTX patients, the average age of symptom onset is 19 years.
• [4] In patients with CTX, central nervous system symptoms and signs are frequently present and can serve as the first manifestation of the disease.
• [5] Clinical signs and symptoms include cataracts, tendon xanthomas (particularly of the Achilles tendon), neurologic abnormalities, and premature atherosclerosis.
• [6] The classical symptoms and signs, namely elevated levels of cholestanol and other lipids in the blood and urine, are diagnostic for CTX.
• [13] Neuropsychiatric symptoms such as behavioral changes, hallucinations, agitation, aggression, depression, and suicide attempts may be prominent.

Diagnostic Evaluation for Cerebrotendinous Xanthomatosis (CTX)

Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder that requires accurate diagnosis to initiate proper treatment. The diagnostic evaluation for CTX typically involves a combination of clinical findings, biochemical testing, neuroimaging, and molecular genetic analysis.

Clinical Findings

A physical exam and review of the patient's medical history and symptoms are essential in diagnosing CTX. During childhood, the condition can manifest with infantile-onset diarrhea, while adolescent- to young adult-onset tendon xanthomas and adult-onset progressive neurologic dysfunction (dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, dystonia, atypical parkinsonism, peripheral neuropathy, and seizures) are common in adults [6][11].

Biochemical Testing

Biochemical testing is a crucial component of diagnosing CTX. Elevated levels of cholestanol in the blood can confirm the biochemical diagnosis of CTX [4]. Molecular genetic analysis of the CYP27A1 gene (included in CHLGP / Cholestasis Gene Panel, Varies) can also confirm the diagnosis [5].

Neuroimaging

Abnormalities on brain magnetic resonance imaging (MRI), such as cerebellar atrophy, decrease in volume of grey and white matter, and abnormal white matter signal, may be observed in patients with CTX [1]. These findings can support the clinical diagnosis.

Molecular Genetic Analysis

Molecular genetic analysis is essential for confirming a diagnosis of CTX. This involves detecting disease-causing mutations in the CYP27A1 gene [3].

Other Diagnostic Tests

Blood screening for CTX using GC-MS measurement of elevated 5α-cholestanol can also be performed [4]. Additionally, biochemical analysis of biomarkers such as Cholestanetetrol glucuronide (Tetrol) and Taurochenodeoxycholic acid (t-CDCA) may be used in the diagnostic evaluation for CTX [8].

References

[1] ... et al: A blood test for cerebrotendinous xanthomatosis with ...

[3] by S Nie · 2014 · Cited by 333 — The diagnosis of CTX is mainly based on clinical findings, biochemical testing, neuroimaging, and molecular genetic analysis.

[4] Blood screening for CTX using GC-MS measurement of elevated 5α-cholestanol can also be performed [4].

[5] Molecular genetic analysis of the CYP27A1 gene (included in CHLGP / Cholestasis Gene Panel, Varies) can also confirm the diagnosis [5].

[8] Biochemical analysis of biomarkers such as Cholestanetetrol glucuronide (Tetrol) and Taurochenodeoxycholic acid (t-CDCA) may be used in the diagnostic evaluation for CTX [8].

Differential Diagnoses for Cerebrotendinous Xanthomatosis (CTX)

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease, and its differential diagnoses include other conditions that present with similar symptoms. Some of the key differential diagnoses for CTX are:

• Familial hypercholesterolemia: This condition is characterized by high levels of low-density lipoprotein (LDL) cholesterol in the blood, which can lead to tendon xanthomas and other symptoms similar to those seen in CTX [4].
• Sitosterolemia: Also known as phytosterolemia, this is a rare genetic disorder that affects the metabolism of plant sterols, leading to their accumulation in tissues and causing symptoms similar to those seen in CTX [6].
• Marinesco-Sjogren syndrome: This is an autosomal recessive disorder characterized by a triad of symptoms including cataracts, short stature, and intellectual disability. While it does not directly present with tendon xanthomas, its symptoms can be confused with those of CTX [1].
• Neuromyelitis optica spectrum disorders: These are conditions that affect the optic nerves and spinal cord, leading to vision loss and other neurological symptoms. While they do not directly relate to lipid metabolism, their symptoms can be confused with those seen in CTX [15].

Key Points

• Differential diagnoses for CTX include familial hypercholesterolemia, sitosterolemia, Marinesco-Sjogren syndrome, and neuromyelitis optica spectrum disorders.
• These conditions present with similar symptoms to CTX, including tendon xanthomas, neurological dysfunction, and other systemic signs.
• Accurate diagnosis of CTX requires a comprehensive evaluation of the patient's medical history, physical examination, and laboratory tests.

References

[1] Gallus GN, Dotti MT, Federico A. Clinical and molecular diagnosis of Cerebrotendinous Xanthomatosis with a review of the mutations in the CYP27A1 gene. [4] Regarding differential diagnoses, sitosterolemia, familial hypercholesterolemia (both of which can also manifest with tendon xanthomas), ... [6] Sitosterolemia, familial hypercholesterolemia (both of which can also manifest with tendon xanthomas), ... Gallus GN, Dotti MT, Federico A. Clinical and molecular diagnosis of Cerebrotendinous Xanthomatosis with a review of the mutations in the CYP27A1 gene. [15] Dutra BG, Da RA, Nunes RH, et al. Neuromyelitis optica spectrum disorders: spectrum of MR imaging findings and their differential diagnosis. Radiographics 2018;38:169–93.