Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.
Humans ; Male ; Adult ; Female ; Xanthomatosis, Cerebrotendinous/pathology* ; Pedigree ; Cholestanetriol 26-Monooxygenase/genetics* ; Mutation ; Ataxia

Cerebrotendinous xanthomatosis is a rare autosomal recessive disease that involves multiple organs, including the peripheral nervous system. The present study is the first to report the ultrasonographic findings of peripheral nerves in a patient with cerebrotendinous xanthomatosis. The patient presented with bilateral Achilles tendon enlargement and foot hypesthesia. Sonographic examination revealed hypoechoic, swollen peripheral nerves with enlarged bilateral Achilles tendons. Since the ultrasonographic findings revealed peripheral involvement, the diagnosis of cerebrotendinous xanthomatosis was established after laboratory and genetic studies along with clinical findings.
Achilles Tendon ; Diagnosis ; Foot ; Humans ; Hypesthesia ; Peripheral Nerves ; Peripheral Nervous System ; Polyneuropathies* ; Ultrasonography* ; Xanthomatosis, Cerebrotendinous*

OBJECTIVETo analyze a case of cerebrotendinous xanthomatosis (CTX) with mental retardation as the initial neurological symptom.

METHODSMedical imaging, histopathological assay and genetic testing were carried out to analyze the patient.

RESULTSNeurological manifestations of the 27-year-old male patient were initiated by mental retardation and subsequently memory lapses, ataxia, spastic paraplegia and fuzzy language. Other symptoms included cataract, xanthomatosis in Achilles tendon, kidney stones and high arches. The total bile acid in serum has risen to 14.7 umol/L. There were symmetrical abnormal signals in bilateral cerebellar dentate nuclei, hypointensities on T1WI and DWI and mixed signals on T2WI. Cholesterol crystallization and cholesterol granulomatous inflammation were found upon pathological examination of the Achilles tendon. The patient was found to have carried a compound heterozygous mutation of the CTX gene, which consisted of two novel mutations including c.379C>T (p.Arg127Trp) in exon 2 and c.1174G>A (p.Glu392Lys) in exon 6 of the CYP27A1 gene.

CONCLUSIONClinicians should be alert to cerebrotendinous xanthomatosis when the patient has mental retardation caused by genetic and metabolic factors beginning at a young age, particularly accompanied with tendinous xanthomatosis and cataracts. CTX can be readily diagnosed by histopathological assay and sequencing of the CYP27A1 gene.

Adult ; Cholestanetriol 26-Monooxygenase ; genetics ; Humans ; Intellectual Disability ; etiology ; Male ; Xanthomatosis, Cerebrotendinous ; complications ; genetics

No abstract available.
Magnetic Resonance Imaging* ; Xanthomatosis, Cerebrotendinous*

No abstract available.
Magnetic Resonance Imaging* ; Xanthomatosis, Cerebrotendinous*

No abstract available.
Cholestanol ; Spinal Cord* ; Xanthomatosis, Cerebrotendinous*

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease caused by sterol 27-hydroxylase (CYP27) deficiency. We report two CTX siblings that were presented with typical manifestations such as achilles tendon xanthomas, mental retardation, progressive gait ataxia, and upper motor signs. Their parents and other three sisters were healthy. Serum cholesterol level was within normal limits for both siblings. The older brother has been treated conservatively with muscle relaxant and dopamine agonist because the disease was so progressive, but the younger sister has been treated with 250 mg/day chenodeoxycholic acid (CDCA) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (simvastatin 40 mg/day) to prevent the progressive neurologic dysfunction.
Achilles Tendon ; Chenodeoxycholic Acid ; Cholestanetriol 26-Monooxygenase ; Cholesterol ; Coenzyme A ; Dopamine Agonists ; Gait Ataxia ; Humans ; Intellectual Disability ; Muscles ; Neurologic Manifestations ; Oxidoreductases ; Parents ; Siblings ; Xanthomatosis ; Xanthomatosis, Cerebrotendinous

Cerebrotendinous xanthomatosis is a rare, inherited lipid-storage disease clinically characterized by tendon xanthoma, progressive neurologic dysfunction(cerebellar ataxia, spinal cord involvement, mental retardation), premature atherosclerosis and cataracts. Substantial elevation of serum cholestanol and urinary bile alcohols with low to normal plasma cholesterol concentrations establishes the diagnosis. Up to now, there have not been any reported case of cerebrotendinous xanthomatosis in Korea. So, we report herein a 36-year-old Korean woman with the clinical features of cerebrotendinous xanthomatosis.
Adult ; Ataxia ; Atherosclerosis ; Cataract ; Cholestanol ; Cholestanols ; Cholesterol ; Diagnosis ; Female ; Humans ; Korea ; Plasma ; Spinal Cord ; Tendons ; Xanthomatosis ; Xanthomatosis, Cerebrotendinous*

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive lipid-storage disease with abnormal deposition of cholesterol and cholestanol in multiple tissues. The disease is caused by mutations in the sterol 27-hydroxylase and characterized by tendon xanthoma, premature cataracts and various neurological manifestations in the central and peripheral nervous systems. A 47-year-old man presented with unsteadiness of gait and weakness on extremities. He had a bilateral cataract extraction at the age of 30 years. Physical examination revealed bilateral elongated mass on Achilles tendons. On neurologic examination, dysarthria, spastic quadriparesis and exaggerated deep tendon reflexes were noted. Surgical excisional biopsy of Achilles tendon revealed a crystalline clefts surrounded by many multinucle-ated giant cells. A moderate degree of cerebral and cerebellar cortical atrophy and focal high signal intensities in sub-cortical white matter were noted on T2-weighted magnetic resonance images. Serum cholestanol was elevated (22 Mg/ml ; normal <2 Mg/ml), while serum cholesterol was normal (186 mg/dl ; normal <250 mg/dl). With clinical, radiologi-cal and biochemical findings, we confirmed a rare case of cerebrotendinous xanthomatosis.
Achilles Tendon ; Atrophy ; Biopsy ; Cataract ; Cataract Extraction ; Cholestanetriol 26-Monooxygenase ; Cholestanol ; Cholesterol ; Crystallins ; Dysarthria ; Extremities ; Gait ; Giant Cells ; Humans ; Middle Aged ; Neurologic Examination ; Neurologic Manifestations ; Peripheral Nervous System ; Physical Examination ; Quadriplegia ; Reflex, Stretch ; Tendons ; Xanthomatosis ; Xanthomatosis, Cerebrotendinous*

Cerebrotendinous Xanthomatosis is a rare inherited autosomal recessive disorder characterized by an increased plasma cholestanol level and the accumulation of sterol in tendon and nervous system. The primary biochemical abnormality is a defect in the synthesis of bile acid due to a lack of hepatic mitochondrial sterol-26-hydroxylase activity. The clinical symptoms usually begin in the 2nd decade and include cataract, xanthoma, and progressive neurological dysfunction. There are variable abnormal findings in the eletrophysiologic and radiologic evaluation. The usual treatment consists of long-term administration of the chenodeoxycholic acid (CDCA or UDCA) or cholic acid, which may correct the biochemical abnormality. We report a case of Cerebrotendinous Xanthomatosis in a 32 year old male patient suffered from gait disturbance and tendon xanthoma in both achilles tendons and left knee area.
Achilles Tendon ; Adult ; Bile ; Cataract ; Chenodeoxycholic Acid ; Cholestanol ; Cholic Acid ; Gait ; Humans ; Knee ; Male ; Nervous System ; Plasma ; Tendons ; Xanthomatosis ; Xanthomatosis, Cerebrotendinous*