Presentation
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]
Entire Body System
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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]
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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]
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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]
Respiratoric
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Aspiration
After 2 years, she was bedridden and died of aspiration pneumonia. [ncbi.nlm.nih.gov]
Lens opacification may require extraction at that time and aspirated lens material may contain lipid-containing vacuoles. [disorders.eyes.arizona.edu]
Gastrointestinal
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Chronic Diarrhea
In Chinese CTX patients, xanthomatosis was the most common symptom while cataracts and chronic diarrhea were less frequent. [ncbi.nlm.nih.gov]
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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]
Musculoskeletal
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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]
Neurologic
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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]
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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]
Workup
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]
Treatment
Oral chenodeoxycholic acid (CDCA) can lead to clinical stabilization, but in a subgroup of patients the disease progresses despite treatment. [ncbi.nlm.nih.gov]
Prognosis
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
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]
Epidemiology
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]
Pathophysiology
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
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]