Japanese neonate with congenital chloride diarrhea caused by SLC26A3 mutation

Congenital chloride diarrhea (CCD) beginning in utero is a rare autosomal recessive inherited disorder characterized by impairment of Cl^?/HCO₃^? exchange in an otherwise normal distal ileum and colon. Life‐long secretory diarrhea is caused by mutations in solute carrier family 26, member 3, (SLC26A3), which disrupt epithelial Cl^?/HCO₃^? transport in the ileum and colon. Although 55 mutations in SLC26A3 have been identified throughout the world, few Japanese cases have been confirmed on genetic analysis. We report the successful treatment of a Japanese neonate with CCD caused by SLC26A3 mutation.     

Treatment of an infant with congenital sodium diarrhea by oral rehydration

We have been following a male case of congenital sodium diarrhea (CNaD), who had a distended abdomen, passed watery stools with high sodium concentration, and showed metabolic acidosis in the first week of life. He also showed hyponatremia, low urine sodium, high serum aldosterone and high renin activity. Other possible causes of secretory diarrhea were ruled out. The initial effective treatment was oral supplements of water and electrolytes lost in the fecal fluid: with this he gained weight, and hyponatremia and metabolic acidosis were corrected. Loperamide hydrochloride was administered to increase intestinal absorption of sodium, as the serum prostaglandin was high. Watery diarrhea then improved, but as he passed acholic stools, we stopped and postponed the treatment for a while; the stools then became watery again. Although diarrhea has persisted, he has not shown any abnormalities in growth or psychomotor development for the first two years of life.     

先天性失氯性腹泻1例临床及基因分析

目的探讨先天性失氯性腹泻的临床特征及其基因变异特点。方法回顾分析1例先天性失氯性腹泻患儿的临床资料及基因分析结果。结果出生15天的女性患儿因出生后皮肤巩膜黄染而入院,入院后患儿偶有腹泻,伴反复腹胀;多次血气、血电解质分析示低钾、低钠、低氯血症及代谢性碱中毒;临床诊断为Bartter综合征,予氯化钠及氯化钾等治疗,血气及电解质基本稳定。基因检测发现患儿SLC26A3基因分别来自母亲和父亲的c.269_270 dupAA、c.735+4_735+7del复合杂合变异,其中c.735+4_735+7del为新的变异,尚未有文献报道。结论确诊临床罕见的先天性失氯性腹泻。     

Mutant neurogenin‐3 in a Turkish boy with congenital malabsorptive diarrhea

Congenital diarrheal disorders are caused by disruption in nutrient digestion, absorption, or transport, enterocyte development and functioning, or enteroendocrine functioning. Many additional rare forms of congenital diarrhea are expected to be linked to genes associated with appropriate intestinal fluid and electrolyte balance. Neurogenin‐3 mutation, a very rare form of congenital diarrhea, disrupts enteroendocrine cell differentiation and is characterized by malabsorption and the absence of pancreatic islet cells. Diabetes mellitus is typically associated with malabsorptive diarrhea at early onset or at later presentation in neurogenin‐3 mutation. Here, we describe the case of an infant with homozygous neurogenin‐3 mutation who had severe malabsorptive diarrhea and episodes of hyperchloremic metabolic acidosis after birth. Remarkably, cholestyramine was effective at reducing stool volume and frequency and improved the consistency of the stools; diabetes was not present in this patient.     

Extremely rare cause of congenital diarrhea: Enteric anendocrinosis

Congenital diarrheal disorders consist of a variety of chronic enteropathies. There are approximately 30 different diseases that can be classified into four groups according to the mechanisms involved in pathogenesis: (i) absorption and transport of nutrients and electrolytes; (ii) enterocyte differentiation and polarization; (iii) enteroendocrine cell differentiation; and (iv) modulation of the intestinal immune response. Affected patients often present with life‐threatening diarrhea, in the first few weeks of life. A new disorder, enteric anendocrinosis, which is characterized by severe malabsorptive diarrhea and a lack of intestinal enteroendocrine cells has recently been described in six patients with recessively inherited mutations in the Neurogenin‐3 gene. In this report we describe a seventh case with a review of the literature.     

A female infant successfully treated by ganciclovir for congenital cytomegalovirus infection

An 11 month old female infant, diagnosed as having congenital cytomegalovirus (CMV) infection and suffering from pneumonia and intractable diarrhea, was treated with 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG), intravenously for 8 weeks. Watery diarrhea ceased and pneumonia associated with massive endotracheal aspirates was reduced. No leukopenia, thrombocytopenia or other side effects were observed during the therapy. The clinical findings suggest that DHPG might be an effective and safe agent for the treatment of both intestinal and lower respiratory CMV infection in young infants.     

先天性糖基化障碍1例临床和基因分析

目的探讨甘露糖磷酸异构酶(MPI)基因突变所致先天性糖基化障碍(CDG)的临床和基因突变特点。方法回顾分析1例因肝肿大而被发现的MPI基因缺陷所致CDG患儿的临床资料,以及患儿及其父母基因检测结果。结果患儿,女,1岁左右发现肝脏进行性肿大,伴慢性腹泻、反复呼吸道感染等;体格检查发现肝脏肋下4 cm、脾脏肋下1 cm;腹部MRI提示肝大伴弥漫性密度改变。采用高通量测序法,发现患儿MPI基因(NM_002435. 2)第4号外显子存在2个杂合错义变异c.391GA,p.Asp131Asn和c.455GA,p.Arg152Gin,均为人群中极低频率的变异;家系分析显示父亲携带c.391GA,p.Asp131Asn错义变异,母亲携带c.455GA,p.Arg152Gin错义变异,确诊为CDG-Ib型。结论 CDG是一组由常染色体隐性遗传引起的糖蛋白合成缺陷的代谢性疾病,基因检测有助于明确诊断。     

阿奇霉素治疗先天性弓形虫病16例随访报告

目的　探讨阿奇霉素治疗先天性弓形虫病的疗效。方法　对有弓形虫病临床表现者 ,检查血弓形虫 (TOX)DNA ,循环抗原 (CAG) ,IgM三项 ,其中一项或一项以上阳性者 ,并排除其它的先天性感染疾病而确定诊断。用阿奇霉素 10mg/kg·d服用 6天 ,停 8天 ,服 2个月 ,间隔 1个月 ,视需要是否继续用药。疗程 2～ 8个 ,平均 5个疗程。随访 2 5～ 5年 ,平均 4年。结果　全部患儿均有效 ,病情逐步好转。 12例治疗 9个月～ 1 5年后复查弓形虫 4项 ,10例全部阴转 ,2例TOX IgG转为阳性。其余 4例作临床随访 ,症状消失。结论　 16例先天性弓形虫感染患儿服用阿奇霉素治疗 ,效果显著 ,未见明显毒副作用 ,患儿依从性好     

Linear growth in early treated children with congenital hypothyroidism

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment ( r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine <40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment ( r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year ( r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.     

Right foot congenital infantile fibrosarcoma treated only with chemotherapy

Congenital infantile fibrosarcoma (CIF) is a rare tumor in childhood. The 5‐year survival rate for CIFs is high and has been reported between 84% and 93%, but limb‐amputation/disarticulation is still a major problem. We report the case of a male newborn with a mass in his right foot. X‐ray and MRI revealed a mass destroying all tarsal, metatarsal, and phalangeal bones. The patient was treated only with VAC chemotherapy and is able to walk normally. Pediatr Blood Cancer 2010;54:618–620. © 2009 Wiley‐Liss, Inc.     

马鞍山、苏州地区5岁以下腹泻儿童轮状病毒G、P分型研究

目的 研究马鞍山和苏州地区5岁以下腹泻儿童轮状病毒G型和P型的分型。方法 对马鞍山和苏州地区5岁以下急性腹泻儿童粪便标本1267份，采用酶联免疫吸附试验和巢式-聚合酶链式反应检测轮状病毒感染和血清型。结果 轮状病毒阳性标本378份，主要来自2岁以下婴幼儿；血清型G型是优势株共250株，其中G1100株，G28株，G3111株，G43株，G93株，混合感染4株，未能分型21株(8．40％)；马鞍山以G1型为主(58．54％)，苏州以G3型为优势株(47．85％)；P基因型两地区流行株为P[4]和P[8]，分别占52．33％和47．67％，G1P[4]成为仅次于G1P[8]的GP组合。结论 在苏州和马鞍山地区5岁以下儿童轮状病毒腹泻中，流行的血清型分别为G3和G1，P基因型流行株为P[4]和P[8]。     

先天性失氯性腹泻相关SLC26A3 c.392C>G(p.P131R)突变体细胞模型的建立及其作用机制的初步研究

目的 建立先天性失氯性腹泻（CCD）相关SLC26A3 c.392C > G（p.P131R）突变体细胞模型并初步研究其生物学功能。方法 根据GenBank中SLC26A3基因序列,设计特异性识别SLC26A3基因392位点的上下游单导RNA（sgRNA）,与酶切后的pSpCas9-puro载体混合构建真核重组表达质粒（pSpCas9-SLC26A3）。将重组质粒和供体DNA模板单链DNA寡核苷酸（ssODN）共转染至Caco-2细胞,采用Taqman基因型分析和Sanger测序鉴定SLC26A3 c.392C > G（p.P131R）在Caco-2细胞中的表达。以野生型Caco-2细胞为正常对照组,以成功表达SLC26A3 c.392C > G（p.P131R）的Caco-2细胞为P131R组,两组细胞分别经100 ng/mL TNF-α诱导并命名为TNF-α组和TNF-α+P131R组,通过电-细胞-基质阻抗传感（ECIS）分析检测上述4组肠上皮细胞单层屏障功能的变化;通过Western blot检测正常对照组和P131R组细胞SLC26A3蛋白的表达变化。结果 成功构建了真核重组表达质粒（pSpCas9-SLC26A3）。Taqman基因型分析和Sanger测序均验证SLC26A3 c.392C > G（p.P131R）表达的Caco-2细胞模型构建成功。ECIS分析显示：与正常对照组相比,P131R组肠上皮细胞单层通透性明显增加（P < 0.05）;同时P131R组细胞经TNF-α诱导后的细胞膜通透性增加更为显著（P < 0.05）。Western blot结果显示：与正常对照组相比,P131R组细胞SLC26A3蛋白的相对表达水平显著降低（P=0.001）。结论 SLC26A3 c.392C > G（p.P131R）可引起SLC26A3蛋白表达下降,从而增加肠上皮细胞单层通透性,引起相关腹泻的发生。     

Sustained attention problems in children with early treated congenital hypothyroidism

Sustained attention was studied in 48 children with early treated congenital hypothyroidism and 35 healthy controls, using a computer-paced and a self-paced continuous performance task. The performance of the patients, particularly those in the low T4 group (38 patients with T4 levels < 50 nmol/1 at neonatal screening), declined in the final stage of the computer-paced task, suggesting a problem in remaining attentive over time. The performance of all children declined in the first and improved in the final stage of the self-paced task. This pattern was most pronounced in the low T4 group, reflecting greater variability in their task performance over time, again indicating a problem in sustaining attention. No correlation was found between onset of treatment and sustained attention. The small size of the intermediate T4 group (10 patients with T4 levels ≥ 250 nmol/1 at neonatal screening) made the results more difficult to interpret and may have concealed a problem with sustained attention in this group.