Cerebrotendinous xanthomatosis presenting with schizophrenia-like disorder:A case report

BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a rare autosomal recessive lipid-storage disorder caused by mutations in CYP27A1.Psychiatric manifestations in CTX are rare and nonspecific,and they often lead to considerable diagnostic and treatment delay.CASE SUMMARY A 33-year-old female patient admitted to the psychiatric ward for presentation of delusions,hallucinations,and behavioral disturbance is reported.The patient presented with cholestasis,cataract,Achilles tendon xanthoma,and cerebellar signs in adulthood and with intellectual disability and learning difficulties in childhood.After the characteristic CTX findings on imaging were obtained,a pathological examination of the Achilles tendon xanthoma was refined.Replacement therapy was then initiated after the diagnosis was clarified by genetic analysis.During hospitalization in the psychiatric ward,the nonspecific psychiatric manifestations of the patient posed difficulty in diagnosis.After the patient’s history of CTX was identified,the patient was diagnosed with organic schizophrenia-like disorder,and psychotic symptoms were controlled by replacement therapy combined with antipsychotic medication.CONCLUSION Psychiatrists should be aware of CTX,its psychiatric manifestations,and clinical features and avoid misdiagnosis of CTX for timely intervention.

Dyslipidemia and H pylori in gastric xanthomatosis

AIM： To investigate the relationship among gastric xanthomatosis （GX）, Hpylori, dyslipidemia, and gastritis in Korea, a well-known Hpylori endemic area.METHODS： A total of 771 patients who had undergone gastroduodenoscopy by one endoscopist were included in this study. Among them, 54 patients with GX were assessed for Hpylori infection and their endoscopic characteristics and serum lipid profiles. The findings were compared with 54 age- and sex-matched control subjects without GX.RESULTS： The prevalence of GX was 7% （54/771） with no sex difference. GX was mainly single （64.8%） and located in the antrum （53.7%）. The mean diameter was 7 ± 3 mm. Mean body mass index （BMI） of patients with GX was 23.1 ± 2.8 and no one was above 30. Compared with the controls, lipid profiles of GX group showed significantly lower HDL-cholesterol （48.8 ± 12.3 vs 62.9 ± 40.5, P = 0.028） and higher LDL-cholesterol （112.9 ± 29.9 vs 95.9 ± 22.4, P = 0.032）. The level of total serum cholesterol, triglyceride and the existence of dyslipoproteinemia were not related to the presence of GX. However, GX showed a close relationship with endoscopically determined atrophic gastritis and histologic severity （24/53, 44.4% vs 8/54, 14.8%, P = 0.0082）. H pylori infection and bile reflux gastritis were not significantly related with GX.CONCLUSION： The prevalence of GX is 7% and it may be an increasing entity in Korea. Moreover, dyslipidemia and atrophic gastritis are found to be related to GX, but lip, H pylori infection is not.

Chinese patient with cerebrotendinous xanthomatosis confirmed by genetic testing: A case report and literature review

BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a treatable autosomal recessive inherited metabolic disorder.It results from a deficiency of sterol 27-hydroxylase(CYP27A1),which is a mitochondrial cytochrome P450 enzyme that catalyzes the hydroxylation of cholesterol and modulates cholesterol homeostasis.Patients with CYP27A1 deficiency show symptoms related to excessive accumulation of cholesterol and cholestanol in lipophilic tissues such as the brain,eyes,tendons,and vessels,resulting in juvenile cataracts,tendon xanthoma,chronic diarrhea,cognitive impairment,ataxia,spastic paraplegia,and peripheral neuropathy.CTX is underdiagnosed as knowledge of the disorder is mainly based on case reports.CASE SUMMARY A Chinese family with CTX consisting of one patient and four heterozygous carriers was studied.The patient is a 47-year-old male,who mainly had psychiatric signs but without some cardinal features of CTX such as cataracts,cerebellar ataxia,pyramidal signs and chronic diarrhea.There was a significant increase in the concentration of free fatty acid compared to normal range.Doppler ultrasound of the urinary system showed multiple left kidney stones,a right kidney cyst,and a hypoechoic area in the bladder,which could move with body position.Sagittal and axial magnetic resonance imaging(MRI)of the right ankle joint showed apparent enlargement of the right Achilles tendon and upper medial malleolus flexor tendon,abnormal thickening of the plantar fat,and a small amount of exudation around the fascia in front of the Achilles tendon.Cerebral MRI suggested white matter(WM)demyelination and slight cerebral atrophy.The diagnosis was confirmed by targeted sequencing,which identified compound heterozygous mutations in exon 2 and intron 7 of the CYP27A1 gene(c.435G>T,c.1263+1G>A).Treatment for 3 wk with a combination of lipid-lowering and antipsychotic therapy improved his psychiatric symptoms and normalized the levels of serum free fatty acid.Sediments in the bladder disappeared after therapy.CONCLUSION CYP27A1 genetic analysis should be the definitive method for CTX diagnosis.This case suggests that urinary system diseases may be neglected in CTX patients.The clinical,biological,radiological,and genetic characteristics of CTX are summarized to promote early diagnosis and treatment of this disease.

Progressive ataxia of cerebrotendinous xanthomatosis with a rare c.255+1G>T splice site mutation:A case report

BACKGROUND Cerebrotendinous xanthomatosis is an autosomal recessive disorder of lipid metabolism caused by the mutation of the CYP27A1 gene encoding sterol 27-hydroxylase,an essential enzyme for the conversion of cholesterol to chenodeoxycholic and cholic acids.Cerebrotendinous xanthomatosis is a rare neurological dis-ease with a wide range of clinical symptoms that are easily misdiagnosed.CASE SUMMARY Here we report the clinical,biochemical,and molecular characterization of a 33-year-old female patient with cerebrotendinous xanthomatosis.The patient developed ataxia and had the typical symptoms of juvenile cataracts,tendon xanthomata,and progressive nervous system dysfunction.Magnetic resonance imaging of the brain revealed bilateral dentate nucleus lesions and white matter abnormalities.This patient was misdiagnosed for 2 years resulting in severe neurological complications.After 2 years of chenodeoxycholic acid treatment,she still presented with ataxia and dysarthria.The pathogenic sites of CYP27A1 were identified as c.255+1G>T and c.1263+1G>T,which were both caused by shear denaturation.CONCLUSION Cerebrotendinous xanthomatosis requires a multidisciplinary diagnosis that must be made early to avoid progressive neurological degeneration.c.1263+1G>T is a known mutation,but c.255+1G>T is a rare mutation site.

CYP27A1 mutation in a case of cerebrotendinous xanthomatosis:A case report

BACKGROUND Cerebrotendinous xanthomatosis(CTX)is a rare autosomal recessive metabolic disease caused by mutations in CYP27 A1.It has a low incidence rate,insidious onset,and diverse clinical manifestations.It can be easily misdiagnosed and can go unrecognized by clinicians,leading to delayed treatment and worsened patient outcomes.CASE SUMMARY A 38-year-old male was admitted to our hospital with a history of unabating unstable posture and difficulty in walking for more than 30 years.Subsequently based on the patient’s medical history,clinical symptoms,magnetic resonance imaging and gene sequencing results,he was finally diagnosed with CTX.Due to the low incidence rate of the disease,clinicians have insufficient knowledge of it,which makes the diagnosis process more tortuous and prolongs the diagnosis time.CONCLUSION Prompt diagnosis and treatment of CTX improve patient outcomes.

Enlarged cauda equina nerve roots in Cerebrotendinous Xanthomatosis

CXT is a rare inherited autosomal recessive lipid storage disease due to the impaired metabolic pathway of cholesterol secondary to a deficiency in 27- sterol hydroxylase, an enzyme in the synthesis of chenodeoxycholic acid (CDCA), a primary bile acid. Abnormal bile acid synthesis leads to elevated plasma Cholestanol (a derivative of cholesterol) accumulation, especially in the lens, central nervous system (CNS) and tendons.

Liver transplantation due to cerebrotendinous xanthomatosis end-stage liver disease

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disease characterized by an increase in plasma concentrations of cholestanol and storage of sterols in mul-tiple tissues, especially tendons and the nervous system (1)Neonatal cholestatic jaundice has been rarely reported, but patients may progress to cirrhosis if effective treatment is not provided. Mutations in theCYP27A1 gene leads to decreased synthesis of bile acid, excessive production of cholestanol, and consequent accumulation of cholestanol in tissues in patients with CTX (2)The liver is rarely affected in these patients;however, neonatal cholestatic jaundice can be self-limiting. Reports on liver transplantation for CTX are lacking. Liver transplantation not only cures the liver disease, but also introduces the normalCYP27A1 gene into the patient, which can be potentially beneficial.

Tumor biomarkers： help or mislead in the diagnosis of xanthogranulomatous cholecystitis？-analysis of serum CA 19-9,carcinoembryonic antigen, and CA 12-5

Background Xanthogranulomatous cholecystitis （XGC） is a rare type of gallbladder inflammation.Unlike other cholecystitis,it can be easily misdiagnosed as gallbladder cancer based on radiological images.In response to misdiagnosis,extended surgical treatments are inappropriately given to patients,which is not beneficial to their health and/or recovery.In this study,we set out to determine whether tumor biomarkers can help to avoid misdiagnosis in patients with XGC.Methods Between January 2005 and January 2012,a total of 37 preoperative patients at Sir Run Run Shaw Hospital were suspicious of having gallbladder cancer and was pathologically confirmed to be XGC after surgical operations.Before operations,all patients received a tumor biomarker test to verify diagnosis,which included serum CA 19-9,carcinoembryonic antigen （CEA）,and CA 12-5.Results A measured amount （54.05％） of cases （20 in 37） had at least one elevation over the thresholds of CA 19-9 （37 IU/L）,CEA （5 ng/ml）,and CA 12-5 （35 IU/L）,which increased the suspicion of malignancy and consequently enhanced the difficulty to make right diagnosis of XGC as benign.45.95％ of cases （17 in 37） had an elevation in CA 19-9.2.70％of cases （one in 37） had an elevation in CEA and 24.32％ of cases （nine in 37） had an elevation in CA 12-5.Analysis with Fisher＇s exact test discovered that the presence of common bile duct stone was a contributor to elevations of CA19-9 in patients with XGC.However,even in cases without common bile duct stones,42.86％ of patients （nine in 21） had elevations of at least one tumor biomarker.Among them,26.09％ of patients （six in 21） had elevations of CA 19-9,with the maximum of 536.29 IU/L.Conclusions The elevations of tumor biomarkers in XGC were frequent,suggesting their inabilities to clarify the disease＇s nature,especially when there was a suspicion of gallbladder cancer.Intraoperative frozen pathology of gallbladder might be a possible solution.However,it is against the en bloc surgical principle and has the potential to cause tumor cell spreading.More research should be conducted,such as the discovery of a novel biomarker,so that XGC can less likely be misdiagnosed as malignancy until the final pathological judgment.

Trauma-related xanthogranulomatous interstitial nephritis: a clinicopathological analysis

Objective: To investigate the pathogenesis, exact nature, histologic feature of xanthogranulomatous interstitial nephritis (XGIN) as well as its significance in clinical medicine. Methods: The medical histories concerned were collected with diagnostic images including CT scanning, ultrasonography, intravenous urography (IVU) and laboratory data being synthesized by comparison with what was discovered during operations and pathologic examinations. Results: All patients were ever struck on their loins or backs by blunt violence over 4-12 years. The diseases were clinically diagnosed as “renal cancer” before, during and after operations, and treated with radical nephrectomy. Located at cortical parts, the tumor focus had penetrated the renal capsules and invaded other organs. However, immunohistochemistry demonstrated that the lesions were xanthogranulomas, not tumors, in which there were stacks of foam cells and lymphocytes with vast extends of fibrotic tissues obliterating the cortical interstitial structures. Urinary tracts yielded no bacterium, obstruction or calculus. Conclusions: XGIN is likely to be one kind of immunologic mediated granuloma following blunt renal trauma. It is imperative to clarify pathogenesis and character of this lesion so as to find out any approach to diagnosis and cure of such an unusual nephropathy.