Unexplained neonatal respiratory distress due to congenital surfactant deficiency

Genetic abnormalities of pulmonary surfactant were identified by DNA sequence analysis in 14 (12 full-term, 2 preterm) of 17 newborn infants with fatal respiratory distress of unknown etiology. Deficiency of adenosine triphosphate-binding cassette protein, member A3 (n = 12) was a more frequent cause of this phenotype than deficiency of surfactant protein B (n = 2).     

Strong evidence for autosomal dominant inheritance of severe congenital neutropenia associated with ELA2 mutations

OBJECTIVE: To investigate cases of severe congenital neutropenia (SCN) to ascertain SCN inheritance after determining that the same sperm donor was used by 4 different families to impregnate mothers. STUDY DESIGN: Because the donor sperm was not available, alternative methods were used to determine whether the sperm donor transmitted SCN. DNA isolated from leukocytes was used to sequence the ELA2 gene in the affected children and their mothers. ELA2 was amplified by polymerase chain reaction (PCR), and the product was sequenced. PCR was also performed with genomic DNA from the mothers and affected children using a set of 22 microsatellite PCR primers on chromosomes 14 and 19 to establish linkage to the paternal allele. RESULTS: None of the mothers had a mutation in ELA2, but all 5 affected children had the same mutation affecting the fourth exon at site S97L. Linkage mapping analysis confirmed that all affected children had the same paternal allele on chromosome 19, which contains ELA2. CONCLUSIONS: Our findings indicate that the father provided consistent haplotypes leading to the expression of SCN in all affected children, supporting an autosomal dominant inheritance in which ELA2 mutations occur.     

Autosomal dominant transmission of a syndrome of anal, ear, renal, and radial congenital malformations

Capillary blood samples obtained from a warmed distal phalanx of the right hand were compared with either temporal or right radial arterial blood samples for PO2, PCO2, and pH in 33 critically ill newborn infants. The blood pressure and skin temperatures of each infant and the ambient oxygen concentration were recorded at the time the blood was sampled. Sixty-eight paired PO2 analyses yielded a regression line close to the line of identity. The mean difference between digital capillary and arterial PO2 was 11.3 +/- 1.4 mm Hg (r = 0.92). The results were similar for the paired PCO2 analyses (r = 0.84) and for the paired pH analyses (r = 0.94). The correlation between arterial PO2 and digital capillary PO2 deteriorated when the systolic blood pressure of the patient was below 35 mm Hg. There was no correlation between skin temperature and capillary-arterial PO2 differences. The frequency of retrolental fibroplasia leading to blindness was not different from that in nurseries that sample umbilical arterial blood routinely.     

Secondary transmission of varicella vaccine virus in a chronic care facility for children

A 16-year-old varicella-seronegative resident at a chronic care facility received varicella vaccine; 15 days later he developed severe varicella. Subsequently, a 13-year-old resident and a 39-year-old health care worker developed mild varicella. We demonstrate that vaccine-strain virus was transmitted to both persons, and that transmission included at least 2 variant vaccine strains.     

Herpes simplex virus type 2 acute retinal necrosis 9 years after neonatal herpes

Many cases of acute retinal necrosis caused by HSV-2 have been reported in children, teenagers, and young adults as a result of reactivation of congenital or neonatal infections, which may have been subclinical. Pediatricians should be aware of this entity and alert to recurrences that may be delayed by years.     

Hepatic steatosis and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Taiwanese infants

OBJECTIVES: To explore the prevalence of hepatic steatosis and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Taiwanese infants with idiopathic intrahepatic cholestasis. STUDY DESIGN: The liver specimens from 69 infants with idiopathic intrahepatic cholestasis were reviewed (1993-2004); 11 of them (14.7%) had hepatic steatosis. Six patients with hepatic steatosis participated in the genetic study for the SLC25A13 gene under parental consent. RESULTS: Infants with cholestasis and hepatic steatosis had lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than those with cholestasis alone. Three of the six infants in the genetic study had homozygous 851del4 mutation; for the others, homozygous 1638ins23 mutation, compound heterozygous 851del4/IVS6+5G-->A mutation, and heterozygous IVS6+5G-->A mutation were found for each one. Eleven of the total 12 alleles (91.7%) were demonstrated to have SLC25A13 gene mutations. CONCLUSIONS: Metabolic and genetic studies for NICCD should be performed in Asian infants with idiopathic intrahepatic cholestasis and hepatic steatosis. The 851del4 mutation on the SLC25A13 gene accounts for the major genotype expression of patients with NICCD in Taiwan.     

Homozygosity for TNSALP mutation 1348c>T (Arg433Cys) causes infantile hypophosphatasia manifesting transient disease correction and variably lethal outcome in a kindred of black ancestry

OBJECTIVE: To determine the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP) defect underlying transiently reversible and variably lethal infantile hypophosphatasia (HPP) in a kindred and to characterize HPP prevalence in black people. STUDY DESIGN: In 1986, we reported temporary correction of severe HPP in an American kindred of black ancestry where "infantile" HPP was fatal in 2 of 3 affected individuals representing 2 sibships. This transient improvement in 1 patient followed efforts to increase TNSALP activity endogenously and suggested dysregulation of the gene (TNSALP). Here, we sequenced the coding exons and splice sites of the kindred's TNSALP alleles and reviewed our 30-year experience with HPP to assess its prevalence in black people. RESULTS: Homozygosity for TNSALP missense mutation 1348C>T (Arg433Cys) accounted for this kindred's infantile HPP. The TNSALP promoter sequence was normal. Modeling of TNSALP(433Cys) suggested compromise of the catalytic site. Ethnicity was identified for the 119 families with HPP studied in St. Louis, and race was ascertained for an additional 159 of our 235 consult and HPP families worldwide. In this experience, only this family was of black ancestry. CONCLUSIONS: Infantile HPP from homozygous TNSALP(433Cys) can remit and thus harbor clues regarding the phenotypic variation and perhaps treatment of HPP.     

Hypothalamo-pituitary hypothyroidism detected by neonatal screening for congenital hypothyroidism using measurement of thyroid-stimulating hormone and thyroxine

The optimal strategy in neonatal screening for congenital hypothyroidism is still a subject of controversy. In Kanagawa Prefecture in Japan, simultaneous thyroid-stimulating hormone (TSH) and T4/fT4 determination has been used, while the results of our program may provide valuable information. Cumulative findings were analysed to determine the type and frequency of thyroid disorders in infants detected by simultaneous TSH and T4/fT4 determination, and the TSH and T4/fT4 screening strategy was validated. A total of 1284130 neonates were screened between October 1979 and September 1997 and infants followed because of low T4/fT4 without elevated TSH (T4 < 51.5 nmol/L or fT4 < 9 pmol/L and TSH < 15 mU/L) were retrospectively analysed. The first survey was carried out within 6 mo of birth and the second in 1998; 258 infants were diagnosed with congenital hypothyroidism at the first medical evaluation, 15 of them with hypothalamo-pituitary hypothyroidism. However, in the second survey, only 8 children were confirmed as having hypothalamo-pituitary hypothyroidism, therefore the incidence detected by the present strategy was 1/160516. Of 8 children with hypothalamo-pituitary hypothyroidism, mental retardation was prevented in 3 owing to early treatment. CONCLUSIONS: Simultaneous measurement of TSH and T4/fT4 is a useful strategy for detecting hypothalamo-pituitary hypothyroidism, but more studies are needed to show the cost-benefits of using this strategy.     

Influence of timing and dose of thyroid hormone replacement on mental, psychomotor, and behavioral development in children with congenital hypothyroidism

OBJECTIVES: To evaluate the influence of initial and postinitial treatment factors on cognitive, psychomotor, and psychological outcome in schoolchildren with congenital hypothyroidism (CH). STUDY DESIGN: We studied 45 patients (19 with severe CH and 26 with mild CH) and 37 control children by correlating initial and postinitial treatment factors (free thyroxine and thyroid-stimulating hormone [TSH] concentrations, and the percentage of overtreatment and undertreatment periods) with the results of neuropsychological tests and behavior (as reported on the Teacher Report Form [TRF]). RESULTS: The global IQ of the children with CH was comparable to that of the controls; visuomotor and verbal scores were lower, and total TRF scores were higher. Ethnic group, previous development, and overtreatment predicted IQ and verbal scores, with higher scores seen for the overtreated patients than for the control children and those patients who had not been overtreated. As initial treatment was less satisfactory, total TRF scores were higher. CONCLUSIONS: Our study suggests that initial and postinitial suboptimal treatment of CH leads to abnormalities in IQ and specific fields. Overtreatment may advance cognitive development in 5-1/2- to 7-year-olds. Suboptimal initial treatment may lead to behavioral problems. We recommend that TSH concentrations be maintained within the normal range in patients with CH.     

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

OBJECTIVES: To test whether secretory immunoglobulin A (sIgA) to human immunodeficiency virus (HIV) antigens in breast milk of HIV-positive women is associated with protection against HIV transmission among breast-fed infants. STUDY DESIGN: Nested, case-control design in which HIV-specific sIgA was measured in breast milk collected from 90 HIV-positive women enrolled in a study in Lusaka, Zambia. Milk samples were selected to include 26 HIV-positive mothers with infected infants (transmitters) and 64 mothers with uninfected infants (nontransmitters). RESULTS: HIV-specific sIgA was detected more often in breast milk of transmitting mothers (76.9%) than in breast milk of nontransmitting mothers (46.9%, P = .009). There were no significant associations between HIV-specific sIgA in breast milk and other maternal factors, including HIV RNA quantities in breast milk, CD4 count, and plasma RNA quantities. CONCLUSIONS: HIV-specific sIgA in breast milk does not appear to be a protective factor against HIV transmission among breast-fed infants.     

CHAMP1基因新发突变致常染色体显性智力障碍40型1例

该患儿为6月龄男婴,表现为智力运动发育迟缓、竖头不稳、全身松软、双手不知主动抓物及特殊面容（眼距稍宽、内眦赘皮、稍内斜视、张口容貌、人中短、低位耳）。基因检测结果回报CHAMP1基因存在新发杂合移码突变,染色体位置为chr13:115089847,核酸改变为c.530delCinsTTT,导致氨基酸改变为p.S177Ffs^*2,从而确诊为CHAMP1基因突变致常染色体显性智力障碍40型。该病例报道提示,对于不明原因智力障碍的患儿,尤其是存在全身性肌张力低下、严重语言障碍者,应考虑CHAMP1基因突变的可能,应尽早进行遗传学检测。     

PLCE1 基因突变致激素耐药型肾病综合征1 例报告并文献复习

目的分析PLCE1基因突变致激素耐药型肾病综合征(SRNS)的临床特征和基因变异特点。方法回顾分析1例确诊的由PLCE1基因突变致SRNS患儿的临床资料,并复习相关文献。结果女性患儿,8岁11月龄,确诊原发性肾病综合征6年余,激素耐药型,病理为局灶节段性肾小球硬化(FSGS)。肾病综合征相关基因检测发现,患儿PLCE1基因存在2个杂合错义变异 c.577GA(p.V193I)和c.2770GA(p.G924S);Sanger 测序验证显示c.577GA(p.V193I)来自患儿母亲(杂合状态),患儿父母均无c.2770GA(p.G924S)变异,为新发变异。这2个变异均为已有报道的致病性突变。结论 PLCE1基因变异可导致常染色体遗传型SRNS。