Three cases of cerebraltendinous xanthomatosis caused by compound heterozygous mutation of CYP27A1 gene / 中华神经科杂志

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive genetic disease caused by mutation of CYP27A1 gene. This article reported three cases with clinical phenotypes of CTX and CYP27A1 gene mutation and analyzed the pedigree with a literature review. All the three CTX cases had c.379C>T (p.Arg127Trp) missense mutation on exon 2 of CYP27A1 gene. They all had compound heterozygous mutation and two cases had new type of exon and intron compound mutation. This article enriched the types of CYP27A1 gene mutations in CTX patients. The primers of CYP27A1 gene should also cover more gene sequences including intron regions.

Xantoma del tendón de aquiles bilateral: debut de xantomatosis cerebrotendinosa / Bilateral achilles tendon xanthoma: cerebrotendinous xanthomatosis debut

OBJETIVO Presentación de un inusual caso de xantomatosis cerebrotendinosa en un paciente de edad cuya primera manifestación fueron xantomas bilaterales del tendón de Aquiles. MATERIAL Y MÉTODOS Mujer de 62 años, que presenta tumoraciones, que presenta tumoraciones sólidas y polilobuladas, en la cara posterior de ambos tendones de Aquiles de 8 años de evolución. El diagnóstico se realizó mediante el hallazgo de hiperlipidemia y estudio genético. Se realió la exóresis quirúrgica parcial de las tumoraciones. RESULTADOS A los 5 años de la cirugía del pie izquierdo y 4 años del pie derecho la paciente estaba asintomática. Presentaba una fuerza para la flexión plantar bilateral de 5/5, pudiendo caminar y subir escaleras sin molestias. Presentaba una escala AOFAS de 85 y 90 puntos en el pie izquierdo y derecho, respectivamente. No hubo recidivas. DISCUSIÓN Los xantomas son depósitos de colesterol en el tejido conectivo de la piel, tendones o fascia, como resultado de una hiperlipoproteinemia. La importancia del caso radica en su sospecha diagnóstica, ya que la xantomatosis cerebrotendinosa suele manifestarse en pacientes de menos de 30 años de edad y en los que se ha recomendado la resección radical de las tumoraciones, e incluso del tendón, debido a las frecuentes recidivas. CONCLUSIÓN En pacientes de mayor edad con lesiones que infiltran el tendón, se puede optar por un tratamiento menos agresivo con un buen resultado clínico.

OBJETIVE Presentation of an unusual case of cerebrotendinous xanthomatosis in an elderly patient whose first manifestation was bilateral Achilles tendon xanthomas. MATERIAL AND METHODS 62-year-old woman presenting solid and polylobed tumors on the posterior aspect of both Achilles tendons for eight years. The diagnosis was made by means of hyperlipidemia and a genetic study. Surgical partial excision of the tumors was performed. RESULTS Five years after surgery on the left foot and four years after the right foot, the patient was asymptomatic. Bilateral plantar flexion force was 5/5, The patient was able to walk and climb stairs without discomfort. AOFAS score was 85 and 90 on the left and right feet, respectively. There were no recurrences. DISCUSSION Xanthomatosis is a genetic alteration with deposits of cholesterol in connective tissue of the skin, tendons or fascia, because of hyperlipoproteinemia. The importance of the present case lies in its diagnostic suspicion, since cerebrotendinous xanthomatosis manifests usually in patients under 30 years of age and in whom radical resection of tumors, and even of the tendon, has been recommended due to frequent recurrences . CONCLUSION In older patients with tumors that infiltrate the tendon, a less aggressive treatment can be chosen with a good clinical result.

Xantomatosis cerebrotendinosa: Reporte de un caso en el Perú: Evaluación clínica integral y estudios de neuroimágenes / Cerebrotendinous Xanthomatosis: Report of a case in Peru: Comprehensive clinical evaluation and neuroimaging studies

Se presenta el caso de una paciente de 73 años de edad que, a los 30 años aproximadamente, comenzó a quejarse de dolor al caminar, localizando la molestia a nivel de las regiones aquilianas, con subsecuente aumento de volumen; al paso del tiempo, estas molestias la obligaron a efectuar consulta médica. Los análisis de laboratorio mostraron severa dislipidemia mixta. Al lado de información de significativa declinación cognitiva, provista por familiares (vgr., (i.e., olvidos frecuentes, desorientación, atención disminuida, concentración pobre), hubo evidencia de ánimo fluctuante, labilidad emocional, crisis ansiosas evolucionando hacia ataques de pánico. El test minicognitivo de Folstein, mostró severo estado demencial y en el examen neurológico se constataron ataxia cerebelosa y signos de piramidalismo parcial. El examen oftalmológico puso en evidencia xantelasmas, cataratas y un denso arco senil. El estudio del cerebro con resonancia magnética (RM) mostró el daño encefálico y signos sugestivos de depósitos del colastenol en el SNC. La presencia de xantomas , los hallazgos oftalmológicos, la demencia definidamente progresiva y la ataxia cerebelosa fueron hallazgos clínicos que permitieron establecer el diagnóstico de xantomatosis cerebrotendinosa.

The case of a 73 years-old woman that, since approximately the age of 30 years started to complain of pain when walking, is presented. The symptom was mainly located in the acchillean regions which, as time advanced, showed gradual volume increase and, finally, forced her to seek medical evaluation. Accompanying relatives reported a several years’ history of gradually increasing cognitive difficulties (i.e., forgetfulness, disorientation, poor attention and concentration), fluctuating mood (from periods of good humor switching to sudden episodes of sadness and crying spells), emotional lability and anxiety crises evolving into brief panic attacks. The Mini-cognitive Fenton Test confirmed severe dementia and the neurological evaluation showed cerebellar ataxia and partial pyramidalism. The ophthalmological examination revealed xanthelasmas, cataracts and dense arcus senilis. Xanthomas were detected in the Achillean tendons of both lower extremities. Auxiliary laboratory and densitometric tests demonstrated mixed dyslipidemia and dorsal-lumbar osteoporosis, respectively, and magnetic resonance imaging of the brain (RMC) confirmed SNC damage and suggested deposits of cholestenol, thus confirming the diagnosis of Cerebroitendinous Xanthomatosis.

Sonographic Findings of Polyneuropathy Associated With Cerebrotendinous Xanthomatosis: A Case Report

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.

A case report on cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare hereditary neuro-metabolic disease in which deposition of cholesterol and cholestanol occurs in various tissues including CNS. It is characterized by juvenile cataract, tendon xanthomas and progressive neurological defects. It is one of a group of neurologic disorder collectively referred to as leukodystrophy, which predominantly affects the CNS white matter. We are presenting a patient with cerebrotendinous xanthomatosis, who is now 36 years old, and shows the natural course of disease in an untreated patient. He presented with xanthomas on Achilles tendon, elbow and knees and showed cerebellar and pyramidal signs. He had recurrent seizures and was mentally subnormal.

Cerebrotendinous Xanthomatosis With Spinal Cord Syndrome

No abstract available.

Mutation analysis of CYP27A1 gene in a patient with cerebrotendinous xanthomatosis / 中国神经精神疾病杂志

Objective To investigate the causative mutations of CYP27A1 gene in a sporadic cerebrotendinous xanthomatosis patient. Methods Genomic DNA was extracted from peripheral blood of the patient and her parents. All exons and splice sites of CYP27A1 gene were amplified by polymerase chain reaction (PCR) followed by Sanger sequenc-ing. 105 healthy unrelated subjects were also sequenced for the novel mutation in CYP27A1. Results A novel splice site mutation c.446+1G>T, a novel missense mutation c.877A>T(p.Met293Leu) and a known missense mutation c.1016C>T (p.Thr339Met) of CYP27A1 gene were identified in the patient. The mother carriers the two novel mutations and the fa-ther the c.1016C>T(p.Thr339Met) mutation. The two novel mutations were absent in 105 control subjects, respectively. Conclusions Our study detected two novel mutations, c.446+1G>T and c.877A>T, as well as a known mutation c.1016C>T, of CYP27A1 in a sporadic cerebrotendinous xanthomatosis patient. Our data provide novel information for the mutational spectrum of the gene, which is applicable in the genetic testing and diagnosis. The data also provide in-sight into the pathogenesis of the disease.

Two Siblings with Cerebrotendinous Xanthomatosis / 대한피부과학회지

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.

Cerebrotendinous xanthomatosis.

We describe two adolescent Indian siblings with cerebrotendinous xanthomatosis with cognitive impairment, progressive neurological deterioration, juvenile cataracts and chronic diarrhea. Both patients had bilateral Achilles tendon xanthomata. Rapid progression of disease was an unusual finding in these cases. Magnetic resonance imaging showed characteristic signal alterations in cerebellar hemispheres, brainstem and posterior cerebral white matter.

Xantomatose cerebrotendínea: relato de dois casos / Cerebrotendinous xanthomatosis: a two-case report

Xantomatose cerebrotendínea é rara condição de natureza genética, na qual se observa redução na atividade da enzima hepática 27-hidroxilase, envolvida no metabolismo e excreção do colesterol. Consequentemente, depósitos de material lipídico (colesterol/colestanol) acumulam-se em diferentes regiões do organismo, principalmente tendões, sistema nervoso central e cristalino. Relatamos dois casos da doença em duas irmãs, mostrando os principais achados de imagem.

Cerebrotendinous xanthomatosis is a rare genetic disorder characterized by a decrease in activity of the hepatic sterol 27-hydroxylase involved in the cholesterol metabolism and excretion. Consequently, lipid (cholesterol/cholestanol) deposition is observed in different regions of the body, especially tendons, central nervous system and eye lens. The present report describes the cases of two sisters affected by this disease, highlighting the main imaging findings.

A Case of Cerebrotendinous Xanthomatosis / 대한피부과학회지

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.

A Case of Cerebrotendinous Xanthomatosis

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.

A Case of Cerebrotendinous Xanthomatosis

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.