Selective immunoglobulin M deficiency associated with disseminated molluscum contagiosum

A 16-year-old girl with disseminated molluscum contagiosum (MC) was found to have a very low level of serum IgM, elevated levels of IgG and IgA, and a high level of IgE. She had normal numbers of peripheral blood IgM⁺, IgG⁺ and IgA⁺ B-lymphocytes but their terminal differentiation into plasma cells could not be induced by pokeweed mitogen (PWM) in vitro. On the other hand, the patient's T-cells showed normal helper functions in the PWM system and normal interferon (IFN) production in vitro. However, the IgM⁺ B-cells can be induced to differentiate into IgM secreting cells by Epstein-Barr virus (EBV), suggesting that the genetic mechanism for synthesis of the component immunoglobulin proteins is present. T-cell functions were impaired, as shown by delayed type cutancous hypersensitivity (DTH) and mitogen response. The data suggest that the selective IgM deficiency of the patient is due mainly to defects in B-cells at the terminal differentiation stage, but immunological abnormalities are present in both B and T-cell systems. Neutrophil functions examined were normal. MC was treated by intravenous injection of IFN without any side effects; however, no clinical improvement was achieved.Abbreviations MC molluscum contagiosum - IFN interferon - DTH delayed type cutaneous hypersensitivity - MNC mononuclear cells - FCS fetal calf serum - PBL peripheral blood lymphocytes - sIg surface Ig - PWM pokeweed mitogen - PHA phytohaemaggulutinin - Con A Concanavalin A - DHEA-SO₂ dehydroepiandrosterone sulphate - E₂ Oestradiol-17 - E₃ Oestriol - TRH thyloid-releasing hormone - PRL prolactin - FITC fluorescein isothiocyanate - FL cells human fibroblasts - EBV Epstein-Barr virus     

Clinical presentations and laboratory investigations in respiratory chain deficiency

Respiratory chain deficiencies have long been regarded as neuromuscular diseases. In fact, oxidative phosphorylation, i.e., ATP synthesis by the respiratory chain not only occurs in the neuromuscular system, indeed, a number of nonneuromuscular organs and tissues are dependent upon mitochondrial energy supply. For this reason, a respiratory chain deficiency can theoretically give rise to any symptom, in any organ or tissue, at any age with any mode of inheritance, due to the twofold genetic origin of respiratory enzymes (nuclear DNA and mitochondrial DNA).     

短链酰基辅酶A 脱氢酶缺乏症患儿临床特点及基因变异分析

目的探讨新生儿短链酰基辅酶A脱氢酶缺乏症(SCADD)基因型与表型的关系。方法回顾分析2015年至2018年,在青岛地区296 627例新生儿中筛查发现的7例SCADD患儿的临床资料。结果研究期间初次筛查可疑阳性人数为4 864例,初筛阳性率为0.16%;经基因检测确诊7例SCADD患儿,确诊阳性率为1/42375。7例患儿中,男性4例、女性3例,基因检测发现5种已知变异、4种未知变异,分别为c.1029+89_90insC、c.1031AG、c.1157GA、c.164CT和c.989GA,c.1130CT、c.1186GA、c.445AT和c.949AG。结论 SCADD基因型与血尿串联质谱筛查结果一致,但与临床表型关系不明确,早期诊断和治疗有助改善预后。     

Primary immune regulatory disorders for the pediatric hematologist and oncologist: A case‐based review

An array of monogenic immune defects marked by autoimmunity, lymphoproliferation, and hyperinflammation rather than infections have been described. Primary immune regulatory disorders pose a challenge to pediatric hematologists and oncologists. This paper focuses on primary immune regulatory disorders including autoimmune lymphoproliferative syndrome (ALPS) and ALPS‐like syndromes, immunodysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) and IPEX‐like disorders, common variable immunodeficiency (CVID), CVID‐like, and late‐onset combined immunodeficiency (CID) disorders. Hyperinflammatory disorders and those associated with increased susceptibility to lymphoid malignancies are also discussed. Using a case‐based approach, a review of clinical pearls germane to the clinical and laboratory evaluation as well as the treatment of these disorders is provided.     

Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia and developmental delay: successful correction with umbilical cord blood transplantation

Purine nucleoside phosphorylase deficiency is a primary immunodeficiency syndrome characterized by the triad of recurrent infection, neurologic dysfunction, and autoimmunity. This patient presented atypically with few infections and normal T-cell function. Progressive lymphopenia, ataxia, and developmental delay led to diagnosis. Umbilical cord blood transplantation corrected the immunodeficiency.     

Risks of alternative nutrition in infancy: a case report of severe iodine and carnitine deficiency

A 7.5-month-old infant with failure to thrive, developmental delay, muscular hypotonia, a visible goitre and severe osteopenia is described. Laboratory examination revealed a markedly increased serum TSH with low free T4, severe iodine and carnitine deficiency. The infant was breastfed until the age of 2.5 months and was then given a mixture of almond extract in water. The mother is a strict vegan and the father a lactovegetarian. The nutritional intake of the child was severely depleted in calories (–46%), calcium (–73%) and iodine (–88%). The restrictive alternative nutrition was responsible for the various deficiency disorders.     

Selective IgA deficiency: Clinical and immunological evaluation of 50 pediatric patients

Fifty children with IgA deficiency were followed for 1 to 4 years from 1975 to 1978. Thirty-five had complete deficiency of serum IgA (<2.5 IU/ml) and 15 partial deficiency (serum IgA below the 10th centile for age). Patients with another associated immunodeficiency, such as ataxia-telangiectasia, were not included. Most children with complete deficiency of IgA had recurrent respiratory and/or gastrointestinal infections, about half with onset in the first year of life, while partial deficiency of IgA has probably little if any importance for anti-infectious immunity but is important in the pathogenesis of atopy. Atopic diseases were frequent in both groups. Chromosomal abnormalities were found in 2 patients: trisomy 21 in one and in the other a ring chromosome 18. No important defects in cellular immunity were detected but some isolated, borderline abnormalities were often present.Dedicated to Prof. Dr. H.-R. Wiedemann on the occasion of his 65th birthday     

儿童嘌呤核苷磷酸化酶缺乏症1例报告并文献复习

目的分析总结儿童嘌呤核苷磷酸化酶缺乏症(PNPD)的临床特征。方法回顾分析1例PNPD患儿的临床资料,并复习相关文献。结果男性患儿,1岁9月龄,因面色苍白伴发热、咳嗽入院,既往有反复上呼吸道感染史,运动发育迟缓。血红蛋白88 g/L,网织红细胞11.35%,直接抗人球蛋白试验阳性,CD4~+/CD8~+ T细胞比值低,尿酸水平低。胸部CT示胸腺发育不良。基因测序发现患儿PNP基因存在c.722TC(p.I241T)纯合变异,其父母均为该变异携带者。患儿确诊为PNPD,于2岁3月龄死于多脏器严重感染。文献检索到78例PNPD病例,发病无性别差异,发生反复感染53例,神经功能障碍51例,自身免疫病21例,继发肿瘤性疾病6例。结论对反复感染、神经功能障碍、自身免疫性疾病、CD4~+/CD8~+T细胞比值降低、血尿酸水平低的患儿,需考虑基因缺陷致免疫缺陷病可能,基因序列分析可协助早期诊断。     

MHC class II deficiency cured by unrelated mismatched umbilical cord blood transplantation: Case report and review of 68 cases in the literature

Siepermann M, Gudowius S, Beltz K, Strier U, Feyen O, Troeger A, Göbel U, Laws HJ, Kögler G, Meisel R, Dilloo D, Niehues T. MHC class II deficiency cured by unrelated mismatched umbilical cord blood transplantation: Case report and review of 68 cases in the literature. Pediatr Transplantation 2011: 15: E80–E86. © 2010 John Wiley & Sons A/S. Abstract: MHC class II deficiency is a rare and fatal form of primary combined immunodeficiency caused by a lack of T‐cell‐dependent humoral and cellular immune response to foreign antigens, which can only be cured by allogenic stem cell transplantation. In the literature search, we identified 68 cases of HSCT in MHC class II deficiency in the last 14 yr. Pre‐ and post‐transplant MHC class II deficiency is complicated by overwhelming viral infections, a high incidence of GvHD, and graft failure with a poor overall survival rate below 50%. We report an eight‐month‐old boy presenting with severe respiratory infections and chronic diarrhea, whose sister died at the age of four yr from septicemia. MHC II deficiency was caused by an RFXANK‐mutation and treated successfully by 4/6 mismatched unrelated CBT after a myeloablative conditioning regimen based on anti‐thymocyte globulin, busulfane, fludarabine, and cyclophosphamide. At present, our patient is well with full immune reconstitution 3 yr after CBT. CB may represent an alternative source of stem cells for children with MHC class II deficiency without a suitable donor.     

Selective IgA deficiency with unusual features: Development of common variable immunodeficiency,Sjögren's syndrome,autoimmune hemolytic anemia and immune thrombocytopenic purpura

We report on a girl with selective IgA deficiency and persistently low complement component 4 (C4) levels compatible with heterozygous C4 deficiency. Deterioration of her serum immunoglobulin levels and transition to common variable immunodeficiency were observed within a 5 year follow-up. She also developed Sjögren's syndrome, autoimmune hemolytic anemia and immune thrombocytopenic purpura While these abnormalities have been described before in various combinations, to our knowledge, they have not been reported in a single individual.     

Long-term outcome of classical 21-hydroxylase deficiency: diagnosis, complications and quality of life

A nationwide search of patients with classical 21-hydroxylase deficiency (21-OHD) was performed in Finland to determine the long-term outcome of the disease. In total, 108 patients were found. Fifty-four patients (50%, 31F, 23M) had deficiency of a salt-wasting form and another 54 (50%, 29F, 25M) had a simple virilizing form of 21-OHD. A significant number of severe complications suggestive of glucocorticoid deficiency was found. There were five deaths (4.6% of all) possibly connected with cortisol deficiency. Ten additional patients (9.3% of all) had been acutely admitted 14 times in all due to symptoms of glucocorticoid deficiency. These symptoms included sudden loss of consciousness, convulsions and severe fatigue. Afterwards, permanent neurological defects were detected in two of these patients. Finally, a cross-sectional study was carried out to establish an estimate of the long-term outcome of the disease. Thirty-two (55%) of the 58 patients aged 16 y or more participated in this study. The patient group did not differ from the general Finnish population in terms of education. Three of the patients (5%) had retired prematurely. Surprisingly, the patients felt that their health-related quality of life, as reported in the RAND-36 questionnaire, was better than that of the general Finnish population ( p = 0.023). However, as a significant number of all patients did not participate in this study, the quality of life evaluation results must be interpreted with caution. In conclusion, a significant number of complications was found among patients treated for classical 21-OHD. Nevertheless, the disease has a favourable outcome in terms of quality of life.     

Aortic thrombosis in a neonate with hereditary antithrombin III deficiency: successful outcome with thrombolytic and replacement treatment

We report the case of a newborn male who presented an aortic thrombosis during the neonatal period and was subsequently diagnosed as having antithrombin III (AT III) hereditary deficiency type I. This hypercoagulable condition is known to predispose young adults to venous thrombosis, but in our patient the primary thrombotic incident affected the arterial vessels within the first few days of life. Combined treatment with thrombolytic agents and AT III concentrates recovered aortic permeability, suggesting that the use of AT III may be beneficial for the treatment of thrombotic complications during the first few days of life.     

Ornithine transcarbamylase deficiency in a male: strict correlation between metabolic control and plasma arginine concentration

In a male with a partial defect of ornithine transcarbamylase (OTC) we observed that maintenance of arginine supply was crucial for adequate metabolic control in conjunction with a low protein diet. The arginine supplement had to be given such that the concentrations of arginine and ornithine in plasma were above 50mol/l. It appears that arginine is needed not only as an essential amino acid for protein synthesis but also as a precursor of ornithine. In this patient the substitution thus aimed at increasing the intramitochondrial ornithine in order to reach a critical substrate concentration for the kinetically abnormal OTC.Abbreviation OTC ornithine transcarbamylase     

遗传性球形红细胞增多症合并G6PD 缺乏1 例报告

目的探讨遗传性球形红细胞增多症(HS)合并葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症的临床表现、发病机制和诊断经验。方法回顾分析1例5岁HS合并G6PD缺乏症患儿的临床表现、实验室检查,并复习国内外相关文献。结果患儿,男,5岁。因面色苍白伴黄疸,疑似地中海贫血就诊。红细胞计数2.65×10~(12)/L,血红蛋白70.50g/L,平均红细胞体积78.61 fl,平均球形红细胞体积66.26 fl,网织红细胞18%;镜检红细胞大小不等,以小细胞为主,球形红细胞约占15%;G6PD活性1.38 NBT;SDS-PAGE电泳和Western-blot均显示患儿带3蛋白部分缺失;基因结果显示,带3蛋白SLC4A1基因,一个位于4号外显子点突变c.113AC,另一个位于6号内含子c.349+27CT(IVS 6 nt+27 CT),确诊HS合并G6PD缺乏症。讨论临床上同时患有HS和G6PD缺乏症十分罕见,双重红细胞缺陷影响溶血诊断。