Symptoma

Cerebrotendinous Xanthomatosis

CTX

We present a case of a 25-year-old Asian Indian woman who presented with gait difficulty, fusiform swellings of bilateral tendo-Achilles and infrapatellar tendons, along with history of bilateral cataract surgery 1 year earlier. [ncbi.nlm.nih.gov]

  • Juvenile Cataract

    Frequently bilateral juvenile cataracts present in early childhood which provides ophthalmologists an opportunity to aid in early diagnosis and initiate treatment. [ncbi.nlm.nih.gov]

  • Family History of Mental Retardation

    Early identification of familial history with mental retardation, xanthomas and cognitive impairment might prevent the progression to this treatable type of dementia. [ncbi.nlm.nih.gov]

  • Death in Infancy

    Some early deaths in infancy have also been reported. The documents contained in this web site are presented for information purposes only. [orpha.net]

  • Chronic Diarrhea

    In Chinese CTX patients, xanthomatosis was the most common symptom while cataracts and chronic diarrhea were less frequent. [ncbi.nlm.nih.gov]

  • Recurrent Diarrhea

    Such juvenile lenticular findings should raise suspicion for this treatable metabolic disorder, especially when in the context of recurrent diarrhea during early childhood. [ncbi.nlm.nih.gov]

  • Osteopenia

    These siblings presented with elevated cholestanol levels and typical manifestations such as tendon xanthomas, cataracts, osteopenia, mental retardation, cerebellar ataxia and peripheral neuropathy. [ncbi.nlm.nih.gov]

    Osteopenia is evident by total body densitometry in untreated individuals. Individuals may have marked thoracic kyphosis. Endocrine abnormalities. [ctxinfo.org]

  • Spastic Gait

    The patient, a 46-year-old Japanese male, developed sensory disturbance of the lower legs at 39 and spastic gait at 46 years of age. [ncbi.nlm.nih.gov]

  • Hyperreflexia

    Clinical examination revealed spastic paraparesis with gait ataxia, hyperreflexia of deep tendon reflexes with bilateral Babinski and Hoffmann signs, and mental retardation (IQ: 50; MATTIS: 118/144). [nature.com]

Although seizures have been frequently noticed as part of CTX manifestations, there have not been reports of CTX being diagnosed in drug-resistant epilepsy diagnostic workup nor of seizure response to chenodeoxycholic acid treatment. [ncbi.nlm.nih.gov]

Results : Laboratory workup revealed cholestanol of 19.6 mmol/L (Reference: 2-12 mmol/L) increased cholestanol/cholesterol rate of 4.55 ( Reference : 0.16 /- 0.05 ) and increased cerebrospinal fluid albumin of 24.4 mg dL (Reference: up to 3.5). [mdsabstracts.org]

MRI studies of the brain are an important component of the diagnostic workup for CTX. It may show bilateral hyperintensity of the dentate nuclei and cerebral and cerebellar white matter. [eyewiki.aao.org]

Oral chenodeoxycholic acid (CDCA) can lead to clinical stabilization, but in a subgroup of patients the disease progresses despite treatment. [ncbi.nlm.nih.gov]

Spinal forms had a less severe prognosis. A delayed diagnosis could contribute to the lack of significant response to treatment. [ncbi.nlm.nih.gov]

Along with the current prevalence, the report also contains a disease overview of the risk factors, disease diagnosis and prognosis along with specific variations by geography and ethnicity. [businesswire.com]

Etiology CTX is caused by mutations in the sterol 27-hydroxylase gene ( CYP27A1 ; 2q33-qter). Sterol 27-hydroxylase catalyzes the first step in the oxidation of the side-chain of sterol intermediates in the bile acid synthesis (BAS) pathway. [orpha.net]

ETIOLOGY – GENETICS CYP27A1 gene codes for the mitochondrial enzyme sterol 27-hydroxylase, which is involved in bile acid synthesis. The CYP27A1 gene is located on chromosome 2q33-qter and contains nine exons. [flipper.diff.org]

Retrospective review of the clinical and epidemiological aspects and mutations of all the patients diagnosed since 1992 in the main reference centers for genetic testing of CTX in Spain. Twenty-five patients from 19 families were identified. [ncbi.nlm.nih.gov]

The Sigma-Tau TMP team was given two main goals: 1) gain an in-depth understanding of the epidemiology of CTX; and, 2) generate a road map for the possible adoption and implementation of a test for CTX in the existing newborn screening panel. [kgi.edu]

Summary Epidemiology More than 300 patients have been reported worldwide. Prevalence is estimated to be approximately 1/50,000 among Caucasians. [orpha.net]

In 1980, defects in mitochondrial sterol 27-hydroxylase were implicated in the biochemical pathophysiology of the disease by Oftebro et al. In 1991, mutations in the gene CYP27A1 were discovered as causative... [flipper.diff.org]

Pathophysiology The primary enzymatic defect in cerebrotendinous xanthomatosis is in mitochondrial sterol 27-hydroxylase, a key enzyme in the complicated process of bile acid synthesis from cholesterol. [emedicine.medscape.com]

In 1980, defects in mitochondrial 27-hydroxylase were implicated in the biochemical pathophysiology of the disease by Oftebro et al [7]. In 1991, mutations in the gene CYP27A1 were discovered as causative [8-10]. [faoj.org]

Cerebrotendinous xanthomatosis: pathophysiological study on bone metabolism. J Neurol Sci. 1993; 115 :67–70. [ PubMed : 8468594 ] Federico A, Dotti MT, Volpi N. Muscle mitochondrial changes in cerebrotendinous xanthomatosis. [ncbi.nlm.nih.gov]

Prevention is particularly significant in light of the availability of early genetic diagnosis and the devastating effects of this illness if not treated. [ncbi.nlm.nih.gov]