The genetics of neonatal hyperinsulinism

Congenital hyperinsulinism (CHI) is the most important cause of persistent hypoglycaemia in the neonate and infant. It is a clinically and genetically heterogeneous entity. The clinical heterogeneity is manifested by severity ranging from extremely severe life-threatening disease to very mild clinical symptoms which may even be difficult to identify. Furthermore, clinical responsiveness to medical and surgical management is extremely variable. Two histopathological forms have been described: a diffuse form of CHI and a focal form of CHI. Recent discoveries have begun to clarify the molecular aetiology of the disease and therefore the mechanisms responsible for its clinical heterogeneity are becoming clearer. Mutations in four different genes have been identified in patients with CHI. Most cases are caused by mutations in genes coding for either of the two subunits of the beta-cell K(ATP) channel (ABCC8 and KCNJ11). In the diffuse form of CHI, the hyperinsulinism is due to a recessive mutation of both alleles of these genes (rare dominant mutations have been described). In the focal form of CHI, two events intervene: first, the inheritance of a paternal ABCC8/KCNJ11 mutation; second, the focal reduction to homozygosity of the mutation during pancreatic development by a localized loss of the maternal 11p15 region. Others cases of CHI are due to rare mutations in the beta-cell enzymes glucokinase (only one family described) and glutamate dehydrogenase in hyperammonaemia-associated hyperinsulinism. However, in as many as 50% of cases, no genetic aetiology has yet been identified.     

Primary hyperparathyroidism: a rare endocrinopathy in children. Two case reports

Primary hyperparathyroidism (PHPT) is thought to be a common disease in adults. However, it is a rare endocrine disorder in children and adolescents. We report two cases of primary hyperparathyroidism in children diagnosed at the Department of Endocrinology and Diabetes (EU and D) in the Children's Hospital (ChH), Kielce. The clinical course of the disease in these cases was fundamentally dissimilar, which confirms the observation that this rare endocrinopathy in children presents various clinical profiles, leading to diagnostic difficulties. In the first case, the severe course of PHPT was observed with signs suggesting a hypercalcemic crisis. In the second case, the patient was in a good condition with a mild hypercalcemia and symptoms limited to the skeleton, due to early identification of the disease. We believe these cases indicate the significant role of calcemia determination as a screening test in the diagnosis of PHPT, including in children.     

The deafness,onycho-osteo-dystrophy,mental retardation syndrome

Summary Two new cases of the D.O.O.R. syndrome are reported. The patients described showed most of the characteristics described by Cantwell (1975) and some others that may represent additional clinical findings of this rare syndrome.     

Disease, frequency-dependent selection, and genetic polymorphisms: experiments with stripe rust and wheat

Abstract.— Pathogens have the potential to maintain genetic polymorphisms by creating frequency-dependent selection on their host. This can occur when a rare host genotype is less likely to be attacked by a pathogen (frequency-dependent disease attack) and has higher fitness at low frequency (negative frequency-dependent selection). In this study, we used wheat genotypes that were susceptible to different races of the pathogen Puccinia striiformis to test whether disease created frequency-selection on its host and whether such selection could maintain polymorphisms for resistance genes in the wheat populations. Four different two-way mixtures of wheat genotypes were planted at different frequencies in both the presence and absence of disease. Disease created frequency-dependent selection on its host in some populations. Unknown factors other than disease also created frequency-dependent selection in this system because, in some instances, rare genotype advantage was observed in the absence of disease. Although the pathogen created frequency-dependent selection on its host, this selection was not sufficient to maintain genetic polymorphism in the host populations. In all cases where frequency-dependent selection occurred only in the diseased plots, one of the two genotypes was predicted to dominate in the population and the same genotype was predicted to dominate in both the presence and absence of disease. Only in cases where frequency-dependent selection was not caused by disease was there evidence that genetic polymorphisms would be maintained in the population. The frequency-dependent selection described in this study is a consequence of epidemiological effects of disease and differs from the time-lagged frequency-dependent selection resulting from coevolution between hosts and parasites. The impact of this direct frequency-dependent selection on the maintenance of genetic polymorphisms in the host population is discussed.     

The non-producer plasma cell myeloma. Report of a case and review of the literature

A case of non-producer multiple myeloma (MM) is described and compared with the previous reports. Some recurrent clinical traits seem to characterize this disease. It is interesting that reported cases seem to show a low aggressivity. Some biological problems connected with this form of disease are discussed.     

一例喉真菌病病例报道并文献复习

目的:探讨喉真菌病的临床特征、诊断要点和治疗方案。方法:回顾我院收治的一例喉真菌病患者的临床病例资料,并对1992年至今国内外报道的类似病例33例进行文献复习。本研究共纳入患者34例,男性16例,女性18例,年龄14-67岁,临床表现以声嘶为主,可伴有咽痛、咽干等咽喉不适感,其中有16例患者被误诊为急性喉炎,27例患者有不同程度的抗生素和(或)糖皮质激素使用史。结果:34例患者中,13例通过病理确诊为喉真菌病。所有患者均予抗真菌药物治疗,其中有1例同时行手术治疗,均治愈。结论:喉真菌病临床罕见,症状无特异性,易误诊,但病理学检查可靠,全身或局部使用抗真菌药物疗效佳,预后良好。     

高通量测序技术在罕见病分子诊疗中的 应用及临床实例分析

罕见病病种繁多,且表型复杂多样,不仅仅体现在疾病间的不同,同一种疾病的不同患者在表型上也可能大相径庭。这种普遍存 在的遗传异质性和临床异质性,使罕见病的诊疗极具挑战。近年来,在后人类基因组计划时代,各种测序技术快速发展,使得大规模测 序如疾病目标基因集测序、全外显子组测序、全基因组测序等成为了现实。高通量测序技术可实现对多个靶基因进行高通量平行测序, 有效节约了成本与时间,越来越广泛地应用到临床疾病分子诊疗领域。分析传统测序技术与高通量测序技术的优缺点,介绍罕见病诊疗 中常用的高通量测序策略,并结合临床实例,综述高通量测序技术在罕见病诊疗中的应用。     

Apollo, sudden death, and Homer's "Odyssey": a warning from the past that we may be unable to eradicate coronary artery disease

Over recent years there has been a gratifying decrease in the incidence of recorded deaths from coronary artery disease in the Western world. The common view is that coronary artery disease is a recent phenomenon, that we have been subject to an epidemic in the mid-20th century that is now tailing off, and that with appropriate risk modification we may eradicate this disease or make it very rare. However, this article examines the cases of sudden, nontraumatic death described in Homer's Odyssey, which dates from c. 800 BCE. The results suggest that a high incidence of death from coronary artery disease may not be a recent phenomenon. Together with other described evidence, this study casts doubt on the view that coronary artery disease is a modern epidemic that can be eradicated.     

Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients

Alström syndrome (AS, OMIM ID 203800) is a rare childhood multiorgan disorder, which is widely studied in non-Arab ethnic patients. The clinical and molecular basis of AS and the mode of disease inheritance in consanguineous Arab populations is not well investigated. Therefore, to identify the molecular basis of AS in familial forms, the present study performed whole exome sequencing of 5 AS patients belonging to 2 different Bedouin families from Saudi Arabia. The present study identified the AS causative rare biallelic mutations in ALMS gene:T376S in exon 5 and S909* in exon 8 for family A and an R2721* in exon 10 (R2721*) for family B. ALMS1 targeted genetic sequencing of healthy population controls and family members has confirmed its extremely rare frequency and autosomal recessive mode of inheritance. The truncating mutations S909* and R2721* could cause the loss of CC domains and ALMS motif on C-terminal end of the protein and creates unstable protein, which eventually undergoes intracellular degradation. The premature protein truncating mutations described in our study may eventually provide further insight into the functional domains of the ALMS1 protein and contribute to the understanding of the phenotypic spectrum of AS. Whole exome sequencing based molecular diagnosis is expected to rule out ambiguity surrounding clinical diagnosis of suspected AS cases.     

Tuberculous orchiepididymitis, meningoencephalitis and hydrocephalus

Tuberculous meningoencephalitis (TBM) is a rare and serious, often fatal presentation of active tuberculosis and account for about 1% of cases. Early diagnosis and prompt treatment of TBM is essential to reduce morbidity and mortality. Here, we report a case of TBM in 60-year-old man. TBM was considered on the basis of clinical presentation, laboratory findings (hyponatraemia), cerebrospinal fluid studies, radiological findings (hydrocephalus on multi-slice computed tomography), and history of orchiepididymitis of unknown origin one year earlier, together with information that the patient originated from Kosovo where incidence of tuberculosis is still high. Mycobacterium tuberculosis was cultured from cerebrospinal fluid on Lowenstein-Jensen medium confirming diagnosis of TBM. Subsequently, acid-fast bacilli (AFB) staining on samples obtained after orchiectomy a year ago was performed, revealing AFB. Anti-tuberculosis therapy is still in course. This is the second case of tuberculous meningoencephalitis with the same disease pattern (i.e. tuberculous orchiepididymitis - meningoencephalitis) in our Department, and this fact was crucial for the presumptive diagnosis and urgent treatment of TBM. The former case was described five years ago.     

Chronic monocytic leukemia terminating in blastic transformation

Chronic monocytic leukemia (CMoL) is a rare disorder, closely related to malignant histiocytosis, but a separate entity. The clinical course of the patient described in this case report was characterized by persistent monocytosis without response to cytotoxic therapy, and a large number of infections. On two occasions a clone of cells containing an extra chromosome 20 was observed. The disease terminated in a phase with rapidly increasing numbers of immature monocytoid cells, corresponding to blastic transformation.     

A patient death attributable to implant-related primary anaplastic large cell lymphoma of the breast

Implant-related primary anaplastic large cell lymphoma (ALCL) of the breast is a rare clinical entity. With increasing attention being paid to this disease, most cases reported to date in the literature have demonstrated indolent clinical courses responsive to explantation, capsulectomy, chemotherapy, and/or radiotherapy. The authors describe a case of bilateral implant-related primary ALCL of the breast that proved refractory to both standard and aggressive interventions, ultimately resulting in patient death secondary to disease progression. The authors situate this case in the context of the current state of knowledge regarding implant-related primary ALCL of the breast and suggest that this entity is generally, but not universally, indolent in nature. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.     

Thyroid cancer in patients with hyperthyroidism

OBJECTIVE: The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. With the aim of assessing the clinical relevance of this association, we have retrospectively analyzed the incidence of thyroid cancer in 425 hyperthyroid patients seen and treated by surgery in our institutions. METHODS: Among these hyperthyroid patients, we observed 241 (56.7%) cases of multinodular toxic goiter, 120 (28.3%) of uninodular toxic goiter and 64 (15%) cases of Graves' disease. RESULTS: Thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients. Histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in 2 cases. Neoplasia was detected in 4 patients with nodular toxic goiter and in 3 with uninodular toxic goiter. None of the patients with Graves' disease had thyroid cancer. During the follow-up of 74 months (range 4-154), there were no deaths or any recurrences. CONCLUSION: Although the occurrence of thyroid cancer in hyperthyroid patients is a rare event, the presence of a 'cold' nodule in a hyperfunctioning thyroid should be carefully evaluated to exclude the presence of concurrent malignancy.     

Recommended Criteria for Cardiac Catheterization in Patients with Aortic Valve Disease

Criteria for selection of patients with aortic valve disease for cardiac catheterization are described, based on a study of 81 cases. Children with aortic stenosis warrant catheterization at the time when the clinical diagnosis is made, but in adults this examination may be deferred until symptoms appear or left ventricular hypertrophy is recognized. In patients with pure aortic insufficiency catheterization may be deferred until symptoms appear. When severe stenosis and insufficiency co-exist, the valve is usually heavily calcified. Thirty-seven per cent of patients with aortic valve disease have co-existing mitral lesions and these patients are usually women, are fibrillating and, as a rule, have atrial enlargement in contrast to those with aortic valve disease only. On rare occasions, patients with mitral valve disease have clinically silent but angiographically demonstrable aortic insufficiency; therefore, aortography should precede open-heart correction of a mitral lesion so as to detect minor degrees of aortic insufficiency.     

"Scleroderma linearis: hemiatrophia faciei progressiva (Parry-Romberg syndrom) without any changes in CNS and linear scleroderma "en coup de sabre" with CNS tumor

Background

Hemifacial atrophy (Parry-Romberg syndrome) is a relatively rare disease. The etiology of the disease is not clear. Some authors postulate its relation with limited scleroderma linearis. Linear scleroderma "en coup de sabre" is characterized by clinical presence of most commonly one-sided linear syndrome. In a number of patients, neurological affection is the medium of the disease. The treatment of both scleroderma varieties is similar to the treatment of limited systemic sclerosis.

Case presentation

We present two cases of a disease: a case of a 49-year-old woman with a typical image of hemifacial atrophy, without any changes of the nervous system and a case of a 33-year-old patient with an "en coup de sabre" scleroderma and with CNS tumor.

Conclusion

We described typical cases of a rare diseases, hemifacial atrophy and "en coup de sabre" scleroderma. In the patient diagnosed with Parry-Romberg syndrome, with Borrelia burgdoferi infection and with minor neurological symptoms, despite a four-year case history, there was a lack of proper diagnosis and treatment. In the second patient only skin changes without any neurological symptoms could be observed and only a precise neurological diagnosis revealed the presence of CNS tumor.     

Kaposi's sarcoma and human chorionic gonadotropin: mechanisms,moieties and mysteries

Kaposi's Sarcoma (KS) is a highly angiogenic neoplasm associated with infection by the human gamma-herpesvirus, HHV-8 or Kaposi's sarcoma herpes virus (KSHV). When in 1872 the Hungarian scientist Moritz Kaposi described the sarcoma, which was later named after him, he was dealing with a rare dermatologic disease. Today, KS is a more common pathology due to its high incidence in AIDS, in immuno-suppressed transplantation patients and, in its endemic form, in Africa. The introduction of highly active antiretroviral therapy (HAART) has led to a drastic reduction of KS incidence in HIV-infected patients, but in some cases KS resists the treatment. KS is more common in men than in women. The observation of spontaneous remissions during pregnancy stimulated investigations into the potential anti-KS activity of the pregnancy hormone human chorionic gonadotropin (hCG). The variable effect in clinical trials using urinary preparations of the hormone (u-hCG) has led to the hypothesis that contaminating moieties present in these preparations may account for the anti-KS effect observed in vitro. While the discrepancy between laboratory tests and clinical trials remains a mystery, little is known about potential anti-KS mechanisms of the hormone itself and/or other active moieties present in u-hCG.     

Amyloidosis cutis dyschromica

Background

Amyloidosis cutis dyschromica is a rarely documented variant of cutaneous amyloidosis. To date, only 26 cases have been reported.

Objective

The purpose of this study was to improve the clinical and histopathological data for this variant of amyloidosis and to highlight the immunohistochemical features of the disease. The published cases were also reviewed.

Methods

We performed a retrospective review of patients with amyloidosis cutis dyschromica in a single centre. The clinical, histopathological and immunohistochemical features were documented and analysed.

Observations

We described 10 cases of amyloidosis cutis dyschromica. Six of them were female. Five patients were from the same family, and the other 5 were sporadic. The distinguishing features of the clinical presentation included generalised mottled hyper- and hypopigmented macules, which were asymptomatic or mild pruritic. The typical onset of the lesions occurred in childhood (n?=?7) and occasionally after puberty (n?=?3). No evidence of systemic amyloidosis deposition was observed in these cases of amyloidosis cutis dyschromica. Amyloid deposits were observed in the papillary dermis and were positive for the Congo red stain. An immunohistochemical study showed that the amyloid expresses cytokeratins CK34βE12 and CK5/6.

Conclusions

We described the largest series of amyloidosis cutis dyschromica to date and reviewed the published patients. This rare disease is featured by generalised mottled hyper- and hypopigmented lesions, and it is a rare variant of primary cutaneous amyloidosis without evidence of systemic amyloid deposition. Positive staining for the cytokeratins CK34βE12 and CK5/6 in amyloidosis cutis dyschromica suggests that the amyloid is derived from keratinocytes.

     

Rare causes of scoliosis and spine deformity: experience and particular features

Background

Spine deformity can be idiopathic (more than 80% of cases), neuromuscular, congenital or neurofibromatosis-related. However, there are many disorders that may also be involved. We present our experience treating patients with scoliosis or other spine deformities related to rare clinical entities.

Methods

A retrospective study of the records of a school-screening study in North-West Greece was performed, covering a 10-year period (1992–2002). The records were searched for patients with deformities related to rare disorders. These patients were reviewed as regards to characteristics of underlying disorder and spine deformity, treatment and results, complications, intraoperative and anaesthesiologic difficulties particular to each case.

Results

In 13 cases, the spine deformity presented in relation to rare disorders. The underlying disorder was rare neurological disease in 2 cases (Rett syndrome, progressive hemidystonia), muscular disorders (facioscapulohumeral muscular dystrophy, arthrogryposis) in 2 patients, osteogenesis imperfecta in 2 cases, Marfan syndrome, osteopetrosis tarda, spondyloepiphyseal dysplasia congenita, cleidocranial dysplasia and Noonan syndrome in 1 case each. In 2 cases scoliosis was related to other congenital anomalies (phocomelia, blindness). Nine of these patients were surgically treated. Surgery was avoided in 3 patients.

Conclusion

This study illustrates the fact that different disorders are related with curves with different characteristics, different accompanying problems and possible complications. Investigation and understanding of the underlying pathology is an essential part of the clinical evaluation and preoperative work-up, as clinical experience at any specific center is limited.     

非结核分枝杆菌肺病临床分离株的菌种鉴定及临床特征分析

为探究非结核分枝杆菌（nontuberculous mycobacterium,NTM）肺病临床分离株的菌种分布及临床特征, 对2017年5月―2018年10月就诊于复旦大学附属中山医院的90例NTM肺病患者的样本进行分析。采用快速全自动分枝杆菌培养和药物敏感检测系统（BACTEC MGIT960 System）或改良罗氏培养法对90例患者的采集样本进行培养,利用基质辅助激光解析/电离飞行时间质谱（matrix assisted laser desorption/ionization time of flight mass spectrometry,MALDI-TOF MS）进行菌种鉴定,并对回顾性分析收集的90例患者的临床资料进行分析。结果NTM菌种鉴定为9种,其中慢速生长分枝杆菌65例,以胞内分枝杆菌（54.4%,49/90）占多数;快速生长分枝杆菌25例,以脓肿分枝杆菌（22.2%,20/90）占多数。90例患者中确诊67例、疑似23例。确诊患者中少见菌种所占比例较低（6.0% vs 26.1%,P = 0.016）。确诊与疑似患者在临床表现方面未见显著差异,但确诊患者有抗NTM治疗史的比例显著高于疑似患者（85.1% vs 4.3%,P < 0.001）。确诊患者中,快速生长NTM肺病患者既往抗结核治疗史的比例显著高于慢速生长组（52.9% vs 24.0%,P = 0.036）。本研究结果为NTM肺病的临床诊治提供了数据参考。