An anti-neutrophil antibody associated with a propylthiouracil-induced lupus-like syndrome

A 15-year-old woman with thyrotoxicosis controlled by propylthiouracil presented with chills, fever, splenomegaly, anemia, thrombocytopenia, leukopenia, hypergammaglobulinemia, immune complexes, a positive anti- nuclear antibody test, and a cellular marrow with normal maturation. Anti-neutrophil antibody was detected by cytotoxicity testing. The activity was restricted to the IgM fraction and was absorbed optimally at 4 degrees C. The antibody activity was recovered in both heat and ether eluates made from granulocytes. Lymphocytes, platelets, and red blood cells failed to absorb reactivity. The antibody did not inhibit superoxide production or bacterial killing. Propylthiouracil was discontinued and all signs and symptoms resolved.     

Hypomorphic PCNA mutation underlies a human DNA repair disorder

Numerous human disorders, including Cockayne syndrome, UV-sensitive syndrome, xeroderma pigmentosum, and trichothiodystrophy, result from the mutation of genes encoding molecules important for nucleotide excision repair. Here, we describe a syndrome in which the cardinal clinical features include short stature, hearing loss, premature aging, telangiectasia, neurodegeneration, and photosensitivity, resulting from a homozygous missense (p.Ser228Ile) sequence alteration of the proliferating cell nuclear antigen (PCNA). PCNA is a highly conserved sliding clamp protein essential for DNA replication and repair. Due to this fundamental role, mutations in PCNA that profoundly impair protein function would be incompatible with life. Interestingly, while the p.Ser228Ile alteration appeared to have no effect on protein levels or DNA replication, patient cells exhibited marked abnormalities in response to UV irradiation, displaying substantial reductions in both UV survival and RNA synthesis recovery. The p.Ser228Ile change also profoundly altered PCNA’s interaction with Flap endonuclease 1 and DNA Ligase 1, DNA metabolism enzymes. Together, our findings detail a mutation of PCNA in humans associated with a neurodegenerative phenotype, displaying clinical and molecular features common to other DNA repair disorders, which we showed to be attributable to a hypomorphic amino acid alteration.     

Increased inflammatory markers in children with familial hypercholesterolaemia

BACKGROUND: While data are abundant on increased levels of inflammatory markers in adult patients with hypercholesterolaemia, such data in children are limited. Therefore, we sought to investigate the degree and character of inflammation in children with heterozygous familial hypercholesterolaemia (FH) by measuring levels of neopterin, high-sensitivity C-reactive protein (hsCRP), and soluble CD40 ligand (sCD40L). MATERIALS AND METHODS: In the present study, we compared the concentration of inflammatory markers in children suffering from heterozygous FH (n = 207) with those in unaffected siblings (n = 84). Furthermore, we investigated the effect of 2-year treatment with pravastatin (20-40 mg qd) or placebo on plasma levels of those markers. RESULTS: Our main finding was that serum levels of neopterin and hsCRP were significantly higher in FH children compared with healthy siblings, whereas sCD40L was not. Body mass index and high-density lipoprotein cholesterol levels were significant independent predictors of hsCRP and neopterin. Furthermore, pravastatin therapy decreased neopterin, but not hsCRP and sCD40L, in the FH children, but these changes were not different from the placebo group. CONCLUSION: These findings indicate low-grade monocyte/macrophage hyperactivity in the early stages of atherogenesis, but our findings also suggest that inflammation as well as anti-inflammatory effects of statins are less prominent features of atherosclerosis in FH children than in FH adults.     

GATA2 mutation underlies hemophagocytic lymphohistiocytosis in an adult with primary cytomegalovirus infection

We report a case of a 27-year old woman with persistent fever and pancytopenia who had multiple episodes of a hemophagocytic lymphohistiocytosis (HLH) like condition. The criterion for HLH was satisfied; primary cytomegalovirus (CMV) infection was identified as the cause. Further examination revealed a GATA binding protein 2 mutation. Reports of GATAs deficiency presenting with HLH after primary CMV infection is very limited. As early recognition and diagnosis will improve patients' outcomes, internists and infectious disease specialists should be aware of this disease.     

Lung transplantation for Williams-Campbell syndrome with a probable familial association

Williams-Campbell syndrome is a rare disorder characterized by deficiency of subsegmental bronchial cartilage and development of airway collapse and bronchiectasis that may subsequently progress to respiratory failure and death. There are only 2 published reports suggesting a familial association, and only one report of lung transplantation being used as a therapeutic modality. Due to postoperative airway complications, transplantation has not been recommended for this disease. We report the first lung transplant with prolonged survival, approaching 10 years, in a patient with Williams-Campbell syndrome, and provide further evidence to support a familial association.     

重视炎症性肠病的皮肤表现

炎症性肠病（inflammatory bowel disease, IBD）患者皮肤表现类型多样,包括炎症累及皮肤的IBD特异性皮肤表现及反应性皮肤表现;与IBD并发的皮肤表现,以及继发于其他原因而出现的IBD继发性皮肤表现。溃疡性结肠炎（ulcerative colitis, UC）患者以结节性红斑、坏疽性脓皮病为多见;克罗恩病（Crohn's disease, CD）患者以皮肤的脓肿和瘘管多见。IBD皮肤表现可以出现在IBD诊断之前、之后或同时,部分特殊类型皮肤表现的出现对IBD诊断具有提示意义。IBD皮肤损害的治疗应以控制IBD病情为基础,根据皮肤损害的类型针对性治疗。     

Usher's syndrome with unusual otologic manifestations.

Usher's syndrome is characterized by a congenital hearing loss and retinitis pigmentosa. Ocular symptoms and signs are usually established at adolescence, and the hearing loss, the onset of which is at a young age, generally remains stable. The following case is of interest, therefore, because the hearing loss that had been present since birth progressed suddenly to total bilateral deafness in adulthood. There were no ocular symptoms at any time; the classic findings of retinitis pigmentosa were disclosed only on routine examination of the eyes.     

Hereditary thrombocytopenia with familial novel mutation in MYH9 gene: A familial case report

One of the rarest types of hereditary thrombocytopenia is the MYH9-related disorder. This spectrum of disorders is characterized by large platelets with or without leukocyte inclusion bodies, a decrease in the total number of platelets, and autosomal dominant inheritance. Proteinuric nephropathy that frequently progresses to end-stage renal failure, as well as the beginning of progressive high-frequency sensorineural hearing loss in young adults, is also associated with MYH9-related disorder. In this case report, we presented three family members who had thrombocytopenia and in whom a heterozygous novel 22 bp deletion (c.4274_4295del) was detected which is located in exon 31 of the MYH9 gene. There was no evidence of bleeding in the family members we presented and thrombocytopenia was detected incidentally. Additionally, renal failure, hearing loss, presenile cataracts, and clinical symptoms were not detected in these family members. This novel mutation detected in the MYH9 gene has not been reported in the literature before.     

Sweet's syndrome associated with systemic inflammatory response syndrome

Septic shock is characterised by infection causing a systemic inflammatory response, end-organ failure and acute circulatory collapse. Treatment consists of antimicrobial therapy and the supportive management of multi-organ failure. We report a case of what we believed to be septic shock due to pyelonephritis in a patient whose condition continued to deteriorate despite conventional treatment until the diagnosis of Sweet's syndrome was made. Once she was started on high dose steroids, her condition improved and she made a full recovery. We believe this to be the first case of a severe systemic inflammatory response syndrome associated with Sweet's syndrome. Received: 20 January 1998 Accepted: 12 June 1998     

A single factor underlies the metabolic syndrome: a confirmatory factor analysis

OBJECTIVE: Confirmatory factor analysis (CFA) was used to test the hypothesis that the components of the metabolic syndrome are manifestations of a single common factor. RESEARCH DESIGN AND METHODS: Three different datasets were used to test and validate the model. The Spanish and Mauritian studies included 207 men and 203 women and 1,411 men and 1,650 women, respectively. A third analytical dataset including 847 men was obtained from a previously published CFA of a U.S. population. The one-factor model included the metabolic syndrome core components (central obesity, insulin resistance, blood pressure, and lipid measurements). We also tested an expanded one-factor model that included uric acid and leptin levels. Finally, we used CFA to compare the goodness of fit of one-factor models with the fit of two previously published four-factor models. RESULTS: The simplest one-factor model showed the best goodness-of-fit indexes (comparative fit index 1, root mean-square error of approximation 0.00). Comparisons of one-factor with four-factor models in the three datasets favored the one-factor model structure. The selection of variables to represent the different metabolic syndrome components and model specification explained why previous exploratory and confirmatory factor analysis, respectively, failed to identify a single factor for the metabolic syndrome. CONCLUSIONS: These analyses support the current clinical definition of the metabolic syndrome, as well as the existence of a single factor that links all of the core components.     

Autosomal dominant familial Mediterranean fever-like syndrome with amyloidosis

We report a pedigree in which a syndrome that resembled familial Mediterranean fever occurred in four family members over three successive generations. All four patients had systemic amyloidosis. Typically, patients with familial Mediterranean fever show an autosomal recessive inheritance pattern. The disorder commonly afflicts Sephardic Jews, Arabs, and persons of Turkish descent. Colchicine therapy dramatically reduces the attack rate of serositis. The family described herein is unique because of their European ethnicity and the autosomal dominant inheritance pattern. Unlike typical familial Mediterranean fever, colchicine had no influence on the attacks and did not prevent amyloidosis in the three patients who received this treatment.     

Novel stop mutation causing familial hypercholesterolemia in a Costa Rican family

Combined heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis of the promoter and coding region of the low density lipoprotein receptor (LDLR) gene revealed a novel C to T mutation at nucleotide position 2056 in a Costa Rican patient with heterozygous familial hypercholesterolemia (FH). This nonsense mutation, Q665X, results in a termination codon in the epidermal growth factor (EGF) precursor homology domain of the mature LDLR.     

VHL综合征合并红细胞增多症超声表现1例

患者女,29岁,已婚未育.自诉口渴多饮,近1个月体质量减轻3 kg.体格检查:精神状态好,体质量指数19.0 kg/m2,血压、呼吸、心率正常,无头晕头痛,无恶心呕吐,无腹痛腹泻,无既往疾病史,无家族遗传病史.实验室检查:空腹血糖12.55 mmol/L,丙氨酸氨基转移酶55.1 U/L,余未见异常.超声检查:胰腺形态...     

Novel missense mutation in the CASR gene in a Chinese family with familial hypocalciuric hypercalcemia

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder characterized by asymptomatic and non-progressive hypercalcemia resulting from loss-of-function mutations of the CASR (calcium-sensing receptor) gene located on chromosome 3, or from mutations in two mapped but unidentified genes located on chromosome 19. METHODS: We report a middle-aged woman incidentally found to have FHH. To determine the molecular basis of FHH in this Chinese family, we performed direct DNA sequencing of the CASR gene of the proband. RESULTS: We found that the proband is heterozygous for a novel missense mutation P798T, confirming the diagnosis of FHH. Family screening showed that all of the offspring with biochemical features of FHH have the P798T mutation. The mutation, P798T, is located in the third intracellular loop of the CASR, possibly affecting the downstream calcium sensing pathway and therefore inactivating the receptor function. CONCLUSIONS: The molecular basis of FHH in a Chinese family was established. The developed mutation detection assay provides a reliable method for identifying FHH carriers.     

LHCGR基因突变所致家族性男性性早熟家系分析

目的:探讨1例家族性男性性早熟(familial male-limited precocious puberty,FMPP)患儿的临床特征,并对黄体生成素/人绒毛膜促性腺激素受体(luteinizing hormone/choriogonadotropin receptor,LHCGR)基因进行突变分析。方法:收集1例2岁5个月FMPP患儿的临床资料,包括性征、实验室相关检查结果等,并对患儿及其父母外周血白细胞LHCGR基因的11个外显子编码区进行测序。结果:患儿身高98 cm,双侧睾丸3.5 mL,阴茎长7 cm、横径2 cm,阴毛PH2期;血睾酮3.09 ng/mL,促黄体生成素基础值<0.1 mU/mL,卵泡刺激素基础值0.2 mU/mL,促性腺激素释放激素激发试验中促黄体生成素峰值0.88 mU/mL、卵泡刺激素峰值1.35 mU/mL,符合外周性性早熟表现。进一步行PCR扩增片段测序显示,LHCGR基因第11外显子1723A>C突变,导致575位氨基酸残基由异亮氨酸变为亮氨酸。患儿母亲检测到相同的基因突变位点,但未出现青春期发育异常。结论:FMPP是外周性性早熟罕见病因,本病例有典型的临床表现,检测发现LHCGR基因杂合突变c.1723A>C(p.Ile575Leu),母子具有相同基因型但表型不同,可能与女性雌激素的产生和卵泡发育需要LH和FSH的共同参与及青春期前女性性腺上不表达或低表达LHCGR有关。     

No certain predictors for mutation status in a Danish cohort with familial hypercholesterolemia: a descriptive study

OBJECTIVE: In order to enable clinicians to refer the right persons suspected of familial hypercholesterolemia (FH) for mutation screening, a retrospective study was conducted in a Danish FH cohort. DESIGN AND METHODS: The study comprised 643 probands and 395 relatives, of which 421 individuals had a pathogenic mutation, and 211 had cardiovascular disease (CVD). Logistic regression, Cox regression, and receiver operating characteristics (ROC) curves were used to find optimal predictive variables for mutation status and evaluate risk factors for CVD. RESULTS: Age alone had significant predictive power in both genders. ROC curves and area under the curve plots found no parameters capable of predicting mutation status. The only significant risk factor for CVD in both genders was mutation carrier status. CONCLUSIONS: No parameters could decipher mutation status a priori. All individuals fulfilling the FH criteria should therefore be referred in order to facilitate family tracing and genetic counseling.     

川崎病休克综合征合并巨噬细胞活化综合征超声表现1例

<正>患儿女,9岁,因“发热伴皮疹5 d,发现颈部包块4 d”入院。自诉5 d前无明显诱因出现发热,体温最高达41.2℃,抗感染治疗后症状改善不明显。体格检查：体温38.2℃、呼吸24次/min、血压100/70 mm Hg(1 mm Hg=0.133 kPa）;神志清,精神不佳;全身红色皮疹,躯干部较密集,红白相间分布;右侧颈部可见一直径约2 cm包块,质软,有触痛,局部皮温较高,浅表淋巴结未触及;双眼结膜充血,口唇充血皲裂,草莓舌,呼吸平稳,咽红,扁桃体Ⅰ度肿大,咽后可见少许脓性分泌物;双肺呼吸音粗,未闻及啰音;心率104次/min,律齐,心音有力,无杂音;腹软,肝、脾未触及,手部及双下肢小腿硬肿,四肢肌张力可,未引出病理反射。