ABSTRACT
Purpose: Xanthomatous hypophysitis (XHP) is an extremely rare form of primary hypophysitis for which there is a lack of clinical experience. A comprehensive understanding of its clinical characteristics, diagnosis and treatment is needed. Methods: Here, we report a case study and conduct a systematic review of XHP. Thirty-six cases were included, and their clinical manifestations, endocrine assessment, imaging features, treatment and follow-up data were collected and analyzed. Results: The mean age at diagnosis was 39.1 years, and females were predominant (75.0%). The most common symptom was headache (68.6%), and 66.7% of female patients presented menstrual disorders. The most common pituitary dysfunction was growth hormone (GH) deficiency. More than half of patients exhibited central diabetes insipidus (CDI). The majority of patients had an imaging presentation of a cystic lesion with peripheral enhancement. Pituitary stalk thickening was observed in half of the patients. Total lesion resection was achieved in 57.1% of cases. The recurrence rate after partial resection and biopsy was significantly higher than that after total lesion resection (57.1% vs. 0.0%, P = 0.0147). The most common pituitary hormone abnormalities to resolve after surgery were hyperprolactinemia (100.0%) and GH deficiency (91.7%). The typical pathological feature was inflammatory infiltration of foamy histiocytes, which showed positivity for CD68. Conclusion: Diagnosis of XHP is difficult when relying on clinical symptoms and imaging features. Therefore, surgical histopathology is necessary. Based on the available evidence, total lesion resection is recommended for treatment. However, the long-term prognosis for this rare disease remains unclear.
Subject(s)
Hypophysitis/diagnosis , Pituitary Gland/diagnostic imaging , Xanthomatosis/diagnosis , Adolescent , Adrenocorticotropic Hormone/blood , Adult , Aged , Child , Female , Follicle Stimulating Hormone/blood , Human Growth Hormone/blood , Humans , Hypophysitis/blood , Hypophysitis/diagnostic imaging , Insulin-Like Growth Factor I/metabolism , Luteinizing Hormone/blood , Male , Middle Aged , Thyrotropin/blood , Xanthomatosis/blood , Xanthomatosis/diagnostic imaging , Young AdultABSTRACT
Gallbladder cancer (GBC) is the most common biliary tract malignancy worldwide. Although a growing number of studies have explored the mechanism of GBC, thus far, few molecules have been discovered that can be utilized as specific biomarkers for the early diagnosis and therapeutic treatment of GBC. Recent studies have shown that exosomes not only participate in the progression of tumors, but also carry specific information that can define multiple cancer types. The present study investigated the expression profiles of coding (or messenger) ribonucleic acids (mRNAs) and non-coding RNAs (ncRNAs, including long non-coding RNAs [lncRNAs] and circular RNAs [circRNAs]) in plasma-derived exosomes from GBC patients. Using high-throughput RNA sequencing and subsequent bioinformatic analysis, a number of differentially expressed (DE) mRNAs, lncRNAs, and circRNAs were identified in GBC exosomes, compared to their expressions in xantho-granulomatous cholecystitis (XGC) exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were then conducted to investigate the potential functions of these DE RNAs. Furthermore, the interaction networks and competing endogenous RNA networks of these DE RNAs and their target genes were investigated, revealing a complex regulatory network among mRNAs and ncRNAs. In summary, this study demonstrates the diagnostic value of plasma-derived exosomes in GBC and provides a new perspective on the mechanism of GBC.
Subject(s)
Cholecystitis/metabolism , Exosomes/metabolism , Gallbladder Neoplasms/metabolism , RNA , Transcriptome/genetics , Xanthomatosis/metabolism , Cholecystitis/blood , Cholecystitis/diagnosis , Cholecystitis/genetics , Exosomes/chemistry , Gallbladder Neoplasms/blood , Gallbladder Neoplasms/diagnosis , Gallbladder Neoplasms/genetics , Humans , Protein Interaction Maps/genetics , RNA/blood , RNA/genetics , RNA/metabolism , Xanthomatosis/blood , Xanthomatosis/diagnosis , Xanthomatosis/geneticsSubject(s)
Atherosclerosis/epidemiology , Eyelid Diseases/diagnosis , Myocardial Ischemia/epidemiology , Xanthomatosis/diagnosis , Atherosclerosis/blood , Atherosclerosis/prevention & control , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cosmetic Techniques/instrumentation , Eyelid Diseases/blood , Eyelid Diseases/epidemiology , Eyelid Diseases/surgery , Humans , Laser Therapy/instrumentation , Laser Therapy/methods , Myocardial Ischemia/blood , Myocardial Ischemia/prevention & control , Risk Factors , Treatment Outcome , Xanthomatosis/blood , Xanthomatosis/epidemiology , Xanthomatosis/surgeryABSTRACT
BACKGROUND: Typhoid (Salmonella typhi and paratyphi) carriers and gall bladder cancer (GBC) are endemic in northern India. Results of previous studies about association of typhoid carriers with GBC are inconsistent. We studied antibodies against Salmonella typhi and paratyphi in serum samples of patients with GBC. METHODS: We performed modified Widal test for antibodies against Salmonella typhi (Vi and O) and Salmonella paratyphi (AO and BO) antigens in patients with GBC (n=100), xanthogranulomatous cholecystitis (XGC, n=24), chronic cholecystitis (CC, n=200) and healthy controls (HC, n=200). RESULTS: Serum antibodies against Salmonella were more frequently positive in GBC (22%) and XGC (29%), particularly in males in age ≥50 years (GBC: 47% and XGC: 50%) vs. HC (0) (p <0.01). Vi antibody was more common in GBC (13%, OR:9.8) and XGC (8%, OR:5.9) than HC (2%). O antibody was more common in GBC (8%, OR: 8.6) and XGC (8%, OR: 9.0) than HC (1%). O antibody was also more common in males with GBC (12%) than CC (1%) and HC (1%) (P=0.02 and p <0.001, respectively). AO (6%) and BO (4%) antibodies were detected in GBC, particularly in males, than HC (0), (p <0.01). Salmonella antibodies were more frequent in GBC with GS than those without GS (50% vs. 20%, OR=3.94, P=0.01). CONCLUSIONS: Salmonella carrier state was more common in GBC and XGC, particularly in elderly males than HC. The Vi antibody was more common in GBC and XGC than HC. Salmonella infection was more common in GBC with GS than those without GS.
Subject(s)
Antibodies, Bacterial/blood , Cholecystitis/microbiology , Gallbladder Neoplasms/microbiology , Salmonella Infections/epidemiology , Salmonella paratyphi A/immunology , Salmonella typhi/immunology , Xanthomatosis/microbiology , Adult , Aged , Case-Control Studies , Cholecystitis/blood , Cholecystitis/complications , Chronic Disease , Female , Gallbladder Neoplasms/blood , Gallbladder Neoplasms/pathology , Humans , Male , Middle Aged , Salmonella Infections/diagnosis , Xanthomatosis/blood , Xanthomatosis/complicationsABSTRACT
Diffuse (generalized) plane xanthoma is a rare normolipemic xanthomatosis, frequently associated with multiple myeloma and monoclonal gammopathy. Its clinical presentation is well described, and in most cases, clinical suspicion is immediate. Rarely, it can clinically present with a diffuse and uniform yellowish discoloration, and in this context, several investigations are required to identify the correct diagnosis. We describe a case characterized by progressive diffuse yellow-orange discoloration lasting about 3 years and classified as carotenoderma in which reflectance confocal microscopy addressed the diagnosis and drove the correct selection of the biopsy site. Definitive diagnosis of diffuse (generalized) plane xanthoma was confirmed later by histological examination.
Subject(s)
Microscopy, Confocal , Multiple Myeloma/diagnosis , Pigmentation Disorders/pathology , Skin Pigmentation , Skin/pathology , Xanthomatosis/pathology , Aged , Biomarkers/blood , Carotenoids/blood , Diagnostic Errors , Female , Humans , Multiple Myeloma/complications , Pigmentation Disorders/blood , Predictive Value of Tests , Xanthomatosis/blood , Xanthomatosis/etiologyABSTRACT
BACKGROUND AND AIMS: Homozygous familial hypercholesterolemia (hoFH) may cause life-threatening atherosclerotic cardiovascular disease in childhood. Lipoprotein apheresis (LA) is considered a pivotal treatment option, but data on its efficacy, safety and optimal performance are limited. We therefore established an international registry on the execution and outcomes of LA in HoFH children. Here we report LA policies and short-term outcomes. METHODS: We approached centers worldwide, involved in LA in children with hoFH for participation. We collected information on clinical and treatment characteristics on patients aged 0-19 years between November 2016 and November 2018. RESULTS: We included 50 children, treated at 15 sites. Median (IQR) LDL-C levels at diagnosis, on medication and on LA were 19.2 (16.2-22.1), 14.4 (10.8-16.7) mmol/L and 4.6 mmol/L, respectively. Median (IQR) time between diagnosis and start of LA was 2.8 (1.0-4.7) years. Six (12%) patients developed cardiovascular disease during that period. Most children received LA either weekly (43%) or biweekly (37%). Seven (17%) patients reached mean LDL-C levels <3.5 mmol/L, all of them treated at least weekly. Xanthomas were present in 42 (84%) patients at diagnosis and disappeared completely in 19 (45%) on LA. Side effects of LA were minor. There were significant differences in LA conduction between sites in terms of frequency, responsible medical specialities and vascular access. CONCLUSIONS: LA is a safe treatment and may effectively lower LDL-C in children with HoFH. However, there is room for improvement with respect to time of onset and optimization of LA therapy in terms of frequency and execution.
Subject(s)
Blood Component Removal , Cholesterol, LDL/blood , Hyperlipoproteinemia Type II/therapy , Adolescent , Age Factors , Biomarkers/blood , Blood Component Removal/adverse effects , Cardiovascular Diseases/blood , Cardiovascular Diseases/prevention & control , Child , Child, Preschool , Down-Regulation , Female , Genetic Predisposition to Disease , Heart Disease Risk Factors , Homozygote , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/genetics , Infant , Infant, Newborn , Male , Phenotype , Registries , Time Factors , Treatment Outcome , Xanthomatosis/blood , Xanthomatosis/prevention & control , Young AdultABSTRACT
BACKGROUND: The association between dyslipidemia and xanthelasma palpebrarum (XP) remains controversial, and no definite evidence has indicated atherosclerosis risk in patients with XP. OBJECTIVE: The present study was a systematic review and meta-analysis to elucidate the association of serum lipid profiles and risk of atherosclerotic diseases with XP. METHODS: We systematically searched for the eligible comparative studies published before April 15, 2019, in the databases of PubMed, Web of Science, Embase, and Cochrane Library. A random-effects model was used to calculate the standard mean difference with 95% confidence interval for each pooled estimate. RESULTS: The qualitative analyses included 15 case-control studies with 854 patients with XP. Compared with the controls, the patients with XP had significantly higher serum levels of total cholesterol and low-density lipoproteins, significantly higher apolipoprotein B levels, and relatively lower apolipoprotein A1 levels, and the carotid intima-media thickness was significantly higher. CONCLUSION: Patients with XP had significantly higher serum levels of atherogenic low-density lipoproteins and bore significantly higher risk of atherosclerosis than the controls. Careful monitoring and targeted intervention for prevention of cardiovascular diseases is essential for these patients.
Subject(s)
Atherosclerosis/epidemiology , Eyelids/pathology , Lipoproteins, LDL/blood , Xanthomatosis/complications , Atherosclerosis/blood , Atherosclerosis/etiology , Atherosclerosis/prevention & control , Case-Control Studies , Humans , Risk Factors , Xanthomatosis/blood , Xanthomatosis/pathologySubject(s)
Hyperlipoproteinemia Type II/complications , Skin Diseases/diagnosis , Xanthomatosis/diagnosis , Child , Cholesterol/blood , Hand , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/diagnosis , Male , Skin Diseases/blood , Skin Diseases/etiology , Xanthomatosis/blood , Xanthomatosis/etiologyABSTRACT
BACKGROUND: Achilles tendons are the most common sites of tendon xanthomas that are commonly caused by disturbance of lipid metabolism. Achilles tendon thickening is the early characteristic of Achilles tendon xanthomas. The relationship between Achilles tendon thickness (ATT) and LDL-C levels, and risk factors of ATT in patients with hypercholesterolemia, have thus far been poorly documented. METHODS: A total of 205 individuals, aged 18-75 years, were enrolled from March 2014 to March 2015. According to the LDL-C levels and the "Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults", all subjects were divided into 3 groups: normal group (LDL-C < 3.37 mmol/L, n = 51); borderline LDL-C group (3.37 mmol/L ≤ LDL-C ≤ 4.12 mmol/L, n = 50); and hypercholesterolemia group (LDL ≥ 4.14 mmol/L, n = 104). ATT was measured using a standardized digital radiography method and the results were compared among the 3 groups. The correlation between ATT and serum LDL-C levels was analyzed by Pearson's correlation, and the risk factors of ATT were determined by the logistic regression model. RESULTS: ATT in borderline LDL-C group was 8.24 ± 1.73 mm, markedly higher than 6.05 ± 0.28 mm of normal group (P < 0.05). ATT in hypercholesterolemia group was 9.42 ± 3.63 mm which was significantly higher than that of normal group (P < 0.005) and that of borderline LDL-C group (P < 0.05). There was a positive correlation between the serum LDL-C levels and ATT (r = 0.346, P < 0.001). The serum LDL-C level was a risk factor (OR = 1.871, 95% CI: 1.067-3.280) while the levels of HDL-C (OR = 0.099, 95% CI: 0.017-0.573) and Apo AI (OR = 0.035, 95% CI: 0.003-0.412) were protective factors of ATT. CONCLUSIONS: ATT might serve as a valuable auxiliary diagnostic index for hypercholesterolemia and used for the assessment and management of cardiovascular disease.
Subject(s)
Achilles Tendon/pathology , Cholesterol, LDL/blood , Hypercholesterolemia/pathology , Xanthomatosis/epidemiology , Adolescent , Adult , Aged , Female , Humans , Hypercholesterolemia/blood , Male , Middle Aged , Risk Factors , Xanthomatosis/blood , Young AdultABSTRACT
BACKGROUND: Familial hypercholesterolemia is a monogenic autosomal dominant dyslipidemia characterized by a permanent and isolated increase of cholesterol carried by low-density lipoproteins. The prevalence of its heterozygous form is estimated between 1/500 and 1/250, and in the absence of specific treatment, this form is responsible for an increase by a factor of 13 of the risk of premature coronary artery disease compared to patients non-affected by the disease. OBJECTIVES: To perform an inventory of the knowledge of heterozygous familial hypercholesterolemia in France for physicians involved in the management of the disease. METHODS: A survey was conducted (by phone and internet) among a representative sample of 495 physicians (cardiologists, endocrinologists/diabetologists, gynecologists, general practitioners) who, in parallel, completed 579 patient records. RESULTS: Thirty-two percent (95% CI [27.8; 36.2]) of physicians reported the difference between polygenic hypercholesterolemia and familial hypercholesterolemia. The presence of tendinous xanthomas, a key element of diagnosis, was spontaneously mentioned by 44% (95% CI [34; 54.2]) of cardiologists. Six percent (95% CI [2.2; 12.6]) of them gave a correct estimate of the prevalence of familial hypercholesterolemia. The likelihood of transmission of heterozygous familial hypercholesterolemia, when one parent is affected, was known for 59% (95% CI [48.7; 68.7]) of surveyed cardiologists. A cascade screening was performed systematically by 4% (95% CI [1.1; 9.9]) of them. Eighteen percent (95% CI [11; 26.9]) of cardiologists gave an accurate estimation of cardiovascular risk of heterozygous familial hypercholesterolemia. Fifty-seven percent (95% CI [46.7; 66.8]) of cardiologists admitted being misinformed about the heterozygous familial hypercholesterolemia and 83% (95% CI [74.1; 89.7]) expressed a need for information about this disease. CONCLUSION: The lack of knowledge of heterozygous familial hypercholesterolemia and its associated cardiovascular risk is probably the cause of a diagnostic default leading to inappropriate management of this disease.
Subject(s)
Cardiology , Cholesterol, LDL/blood , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Hyperlipoproteinemia Type II/diagnosis , Hyperlipoproteinemia Type II/epidemiology , Physician's Role , Biomarkers/blood , Cholesterol, LDL/genetics , Coronary Artery Disease/blood , Coronary Artery Disease/genetics , France/epidemiology , Genetic Predisposition to Disease , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/genetics , Predictive Value of Tests , Prevalence , Risk Factors , Sensitivity and Specificity , Surveys and Questionnaires , Workforce , Xanthomatosis/bloodABSTRACT
BACKGROUND: Xanthelasma is the most common type of cutaneous xanthoma and often occurs on the eyelids. Xanthoma has been reported to be highly correlated with abnormal lipoprotein metabolism. AIMS: In this study, we wanted to investigate the effects of a high-cholesterol diet on xanthoma formation and lipoprotein metabolism in rabbits. METHODS: In animals fed with high-cholesterol diet, deteced plasma lipid [ie, total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (L-DLC)] levels and pathology of xanthoma. RESULTS: Plasma lipid levels were dramatically elevated within 8 weeks. In addition, high dietary cholesterol promoted xanthoma formation on the napex. Microscopic examination showed that foam cells laden with cholesterol deposits accumulated around the dermal capillaries and cutaneous appendages within the skin of the napex. CONCLUSION: These findings indicate a critical role for a high-cholesterol diet in the dysregulation of lipoprotein metabolism and the development of xanthoma in rabbits. The results suggest that abnormal lipid metabolism may increase the occurrence of xanthoma.
Subject(s)
Cholesterol, Dietary/adverse effects , Lipoproteins/blood , Xanthomatosis/etiology , Xanthomatosis/pathology , Animals , Biopsy, Needle , Cholesterol, Dietary/administration & dosage , Diet, High-Fat/adverse effects , Disease Models, Animal , Humans , Immunohistochemistry , Rabbits , Random Allocation , Reference Values , Xanthomatosis/bloodABSTRACT
AIM: To gain knowledge of xanthelasma, a large population-based study was conducted. METHODS: Patients who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China during Jan 2009 to Nov 2016 were included. General characteristics as well as clinical data were collected, including blood routine, serum biochemical analysis, endoscopic findinds, histological evaluation and comorbiditie. Statistical analyses was performed using SPSS 20.0 software for Windows (IBM Inc., Chicago, IL, United States) using Student's t-test, Mann-Whitney U test, χ2 test, univariable and multivariable logistic analysis. 2-tailed P value less than 0.05 was considered to be statistically significant. RESULTS: A total of 176006 endoscopies were retrieved and we included 1370 xanthelasma participants (703 men, 667 women) in this study. Prevalence of xanthelasma was 0.78% with average age of 56.6 ± 11.2 years. Chief complaint of xanthelasma consisted abdominal pain (24.2%), up-abdominal discomfort (14.1%), abdominal distention (10.1%), dyspepsia (9.1%), et al. Most xanthelasma occurred as single lesion in gastric antrum. Xanthelasma patients witnessed higher Helicobacter pylori (H. pylori) infection rate, more of other gastric lesions including atrophy, intestinal metaplasia and dysplasia (P < 0.01). In xanthelasma patients, serum carcinoembryonic antigen, triglyceride, fasting glucose, neutrophil, neutrophil-to-lymphocyte ratio were significantly higher, and high density lipoprotein-cholesterol, lymphocyte was lower (P < 0.05). Xanthelasma accompanied with more fatty liver disease and hepatic cyst, but fewer gallbladder polyp (P < 0.05). In logistic regression, it revealed that fasting plasma glucose (OR = 3.347, 1.170-9.575, P < 0.05), neutrophil (OR = 1.617, 1.003-2.605, P < 0.05), and carcinoembryonic antigen (OR = 2.011, 1.236-3.271, P < 0.01) were all independent risk factors in xanthelasma. CONCLUSION: Current study described a large xanthelasma cohort in Chinese population, revealed its relationship with H. pylori infection, carcinogenesis, metabolic dysfunction and inflammation as well.
Subject(s)
Gastric Mucosa/pathology , Helicobacter Infections/epidemiology , Pyloric Antrum/pathology , Stomach Diseases/epidemiology , Xanthomatosis/epidemiology , Adult , Aged , Atrophy/blood , Atrophy/diagnostic imaging , Atrophy/epidemiology , Atrophy/pathology , Blood Glucose/analysis , Carcinoembryonic Antigen/blood , China/epidemiology , Female , Gastric Mucosa/diagnostic imaging , Gastroscopy , Helicobacter Infections/blood , Helicobacter Infections/diagnostic imaging , Helicobacter Infections/microbiology , Helicobacter pylori/isolation & purification , Humans , Male , Metaplasia/blood , Metaplasia/diagnostic imaging , Metaplasia/epidemiology , Metaplasia/pathology , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/pathology , Prevalence , Pyloric Antrum/diagnostic imaging , Retrospective Studies , Risk Factors , Stomach Diseases/blood , Stomach Diseases/diagnostic imaging , Stomach Diseases/microbiology , Xanthomatosis/blood , Xanthomatosis/diagnostic imaging , Xanthomatosis/microbiologySubject(s)
Bone Marrow Neoplasms , Hypertriglyceridemia , Tomography, X-Ray Computed , Xanthomatosis , Bone Marrow Neoplasms/blood , Bone Marrow Neoplasms/diagnostic imaging , Humans , Hypertriglyceridemia/blood , Hypertriglyceridemia/diagnostic imaging , Male , Middle Aged , Xanthomatosis/blood , Xanthomatosis/diagnostic imagingABSTRACT
BACKGROUND AND AIMS: There is controversy on the accuracy of different diagnostic criteria for familial hypercholesterolemia (FH). The aim of this study is to assess the performance of different clinical criteria used to identify individuals for FH genetic cascade screening in Brazil. METHODS: All index cases (IC) registered in the Hipercol Brasil program between 2011 and 2016 were analyzed. Inclusion criteria were age ≥18 years and elevated LDL-cholesterol (LDL-C) levels, with a conclusive result in the genetic test, whether positive or negative. Initially, we tested the multivariable association between clinical and laboratory markers and the presence of an FH causing mutation. Then, we analyzed sensitivity, specificity, positive and negative predictive values for the LDL-C quartile distribution, LDL-C as a continuous variable, as well as the performance measures for the Dutch Lipid Clinic Network (DLCN) score to identify a mutation. RESULTS: Overall, 753 ICs were included and an FH causing mutation was found in 34% (n = 257) of the subjects. After multivariable analysis, LDL-C as a continuous variable, tendon xanthomas and corneal arcus were independently associated with the presence of FH mutations. LDL-C values ≥ 230 mg/dL (5.9 mmol/L) had the best tradeoff between sensitivity and specificity to diagnose a mutation. The DLCN score presented a better performance than LDL-C to identify a mutation, area under the ROC curve were 0.744 (95% CI: 0.704-0.784) and 0.730 (95% CI: 0.687-0.774), respectively, p=0.014. CONCLUSIONS: In our population, LDL ≥230 mg/dL is a feasible criterion to indicate ICs to genetic testing.
Subject(s)
Cholesterol, LDL/blood , DNA Mutational Analysis , Genetic Testing/methods , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/genetics , Mutation , Adult , Aged , Arcus Senilis/blood , Arcus Senilis/genetics , Area Under Curve , Biomarkers/blood , Brazil , Chi-Square Distribution , Clinical Decision-Making , Feasibility Studies , Female , Genetic Predisposition to Disease , Humans , Hyperlipoproteinemia Type II/diagnosis , Logistic Models , Male , Middle Aged , Multivariate Analysis , Patient Selection , Phenotype , Predictive Value of Tests , ROC Curve , Reproducibility of Results , Risk Factors , Up-Regulation , Xanthomatosis/blood , Xanthomatosis/geneticsABSTRACT
Essentials Diagnosis of sitosterolemia, a rare recessive or syndromic disorder, is usually delayed. Peripheral blood smear is extremely useful for establishing the suspicion of sitosterolemia. High-throughput sequencing technology enables the molecular diagnosis of inherited thrombocytopenias. Accurate characterization of sitosterolemia helps us determine appropriate management. SUMMARY: Background Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in the ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PSs) usually result in xanthomas and premature coronary atherosclerosis, although hematologic abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis. Objectives To report two novel ABCG5 variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL. Patient/Methods A 46-year-old female was referred to us with lifelong macrothrombocytopenia. She showed familial hypercholesterolemia-related xanthomas. Molecular analysis was performed with high-throughput sequencing. Plasma PS levels were evaluated with gas-liquid chromatography. The STSL landscape was reviewed with respect to specific online databases and all reports published since 1974. Results A blood smear revealed giant platelets and stomatocytes. Novel compound heterozygous variants were detected in exons 7 (c.914C>G) and 13 (c.1890delT) of ABCG5. The patient showed an increased plasma level of sitosterol. These findings support the diagnosis of STSL. In our review, we identified only 25 unrelated STLS patients who presented with hematologic abnormalities including macrothrombocytopenia. It remains unknown why only some patients develop hematologic abnormalities. Conclusions This is the first Spanish STSL patient to be reported and molecularly characterized. The early diagnosis of STLS is strongly supported by the presence of stomatocytes in blood smears. The definitive diagnosis of STSL by measurement of serum PS levels and molecular analyses prompted the use of ezetimibe therapy.
Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics , Hypercholesterolemia/genetics , Intestinal Diseases/genetics , Lipid Metabolism, Inborn Errors/genetics , Lipoproteins/genetics , Mutation , Phytosterols/adverse effects , Thrombocytopenia/genetics , Xanthomatosis/genetics , Anticholesteremic Agents/therapeutic use , DNA Mutational Analysis , Ezetimibe/therapeutic use , Female , Genetic Predisposition to Disease , High-Throughput Nucleotide Sequencing , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/diagnosis , Hypercholesterolemia/drug therapy , Intestinal Diseases/blood , Intestinal Diseases/diagnosis , Intestinal Diseases/drug therapy , Lipid Metabolism, Inborn Errors/blood , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/drug therapy , Middle Aged , Phenotype , Phytosterols/blood , Phytosterols/genetics , Sitosterols/blood , Spain , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Xanthomatosis/blood , Xanthomatosis/diagnosisABSTRACT
AIM: We studied the frequency of Achilles tendon xanthoma (ATX) in patients with acute coronary syndrome (ACS). Furthermore, we investigated the differences in clinical findings between ACS patients with and without ATX. METHODS: Patients with ACS (n=335) were admitted to the coronary care unit of Nippon Medical School between July 2011 and December 2014. Informed consent for the measurement of Achilles tendon thickness (ATT) on a radiograph was obtained from 228 patients without tendon rupture. ATT of each side was measured on the radiograph in patients with ACS and in those with acromegaly (n=18), non-familial hypercholesterolemia (non-FH; n=96), and familial hypercholesterolemia (FH; n=31). RESULTS: ATT of the right and left side in ACS patients were 6.9±1.3 and 7.0±1.6 (mm; mean± SD). In acromegaly, non-FH, and FH patients, ATT of the right/left side were 6.6±1.1/6.7±1.1, 6.2±0.9/6.6±1.0, and 9.4±3.3/10.0±3.1, respectively. ATX (ATT ≥9 mm) was found in 26 (11.4%) patients with ACS. Patients with acromegaly and non-FH had no ATX, whereas all patients with FH had ATX. No differences in age and serum lipid profiles were observed between ACS patients with and without ATX. The levels of body mass index and glycated hemoglobin of ACS patients with ATX were significantly greater than those in ACS patients without ATX (26.8±4.0 vs. 23.9±3.3, pï¼0.05, and 6.9±1.4% 6.3±1.3%, pï¼0.05, respectively). CONCLUSION: This is the first report in which the frequency of ACS patients with ATX was 11.4%. The serum lipid profiles of ACS patients with ATX were similar to those without ATX. In the future, ACS patients with ATX will be diagnosed as having FH.
Subject(s)
Achilles Tendon , Acute Coronary Syndrome/complications , Xanthomatosis/complications , Achilles Tendon/diagnostic imaging , Acromegaly/blood , Acromegaly/complications , Acromegaly/diagnostic imaging , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnostic imaging , Adult , Aged , Body Mass Index , Female , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Hypercholesterolemia/diagnostic imaging , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/complications , Hyperlipoproteinemia Type II/diagnostic imaging , Lipids/blood , Male , Middle Aged , Xanthomatosis/blood , Xanthomatosis/diagnostic imagingABSTRACT
BACKGROUND: Although many factors are involved in the etiology of xanthelasma palpebrum, lipid disorder is strongly associated with its induction. Xanthelasma palpebrum, the most common type of xanthoma, usually presents in middle-aged females and results in aesthetic problems. OBJECTIVE: To evaluate thelipid profile and important clinical aspects of xanthelasma palpebrum patients. METHODS: In this descriptive study, we enrolled 42xanthelasma palpebrumpatients, and 42 cases of non-inflammatory skin disorders as thecontrol group, matched for age and gender.The clinical characteristics of the patients and fasting serum lipid profile were recorded for both groups. The data obtained were analyzed using SPSS-16. RESULTS: Xanthelasma palpebrum was found more commonly in middle-aged females with disease onset of less than 1 year, and without significant familial history of xanthoma. Furthermore,xanthelasma lesionswere most often seen in the upper lid with mild extension and was rarely associated with systemic disease. There was no statistically significant difference between two groups regarding hypertriglyceridemia (p= 0.231) and hypercholesterolemia (p= 0.302). The mean serum levels of cholesterol (221.51±60.4 mg/dl), triglyceride (185.98±71.1 mg/dl) and VLDL (37.7±17.6 mg/dl) were significantly higher and themedian HDL (36.2 (31, 41) mg/dl) level was lower in thepatient group. CONCLUSION: In our study, hypercholesterolemia and hypertriglyceridemia did not reveal a significant difference between thepatient and control groups; however, mean serum values for cholesterol, triglyceride, VLDL and HDL showed a significant difference between the two groups. Therefore, in addition to lipid abnormality, other factors could be involved in the pathogenesis of xanthelasma palpebrum.
Subject(s)
Cholesterol/blood , Eyelid Diseases/blood , Eyelid Diseases/pathology , Triglycerides/blood , Xanthomatosis/blood , Xanthomatosis/pathology , Adult , Dyslipidemias/blood , Dyslipidemias/complications , Eyelid Diseases/etiology , Female , Humans , Male , Middle Aged , Reference Values , Severity of Illness Index , Statistics, Nonparametric , Xanthomatosis/etiologyABSTRACT
Tendinous xanthomas are often thought to be pathognomonic for familial hypercholesterolemia. In this report, we present the case of a young man with a normal lipid profile and Achilles tendon xanthoma. Biochemical and genetic studies confirmed the diagnosis of cerebrotendinous xanthomatosis in this patient. Cerebrotendinous xanthomatosis is a rare autosomal recessive disease associated with xanthoma in tendons and the brain as well as progressive neurologic deficits. Unfortunately, this rare form of reversible dementia is thought to be underdiagnosed. Early diagnosis and treatment of this disease with chenodeoxycholic acid is essential and has been shown to greatly improve the patient's symptoms and prognosis.