Lack of association between Kawasaki syndrome and Chlamydia pneumoniae infection: an investigation of a Kawasaki syndrome cluster in San Diego County

BACKGROUND: The etiology of Kawasaki syndrome (KS), the leading cause of acquired coronary artery disease in children, is unknown. Recent studies have suggested that Chlamydia pneumoniae, a common respiratory pathogen associated with an increased risk of heart disease, might lead to KS. OBJECTIVE: To assess whether KS was associated with an elevated risk of having a current or antecedent infection with C. pneumoniae. METHODS: Blood, urine and pharyngeal specimens from KS patients in San Diego County, CA, during a period of high KS incidence were analyzed for evidence of recent C. pneumoniae infection by culture, PCR and serology. Specimens collected from two control groups, family members of KS patients and age-matched children attending outpatient clinics for well child visits, were similarly analyzed. RESULTS: Thirteen cases were identified. Forty-five outpatient controls and an average of three family members per patient were enrolled in the study. All specimens tested negative for the presence of C. pneumoniae by PCR and culture except for one blood specimen from the mother of a case-patient. Serologic analysis of patients and a subset of outpatient and family controls revealed no evidence of current C. pneumoniae infection; 4 of 13 adult family controls had IgG titers consistent with past exposure to C. pneumoniae. Case patients were no more likely than outpatient controls to have had a respiratory illness in the preceding 2 months (11 of 13 patients vs. 35 of 45 controls; odds ratio, 1.57; 95% confidence interval, 0.3 to 11.9). CONCLUSIONS: We found no evidence that C. pneumoniae infection was associated with KS.     

An evaluation of hospitalizations for Kawasaki syndrome in Georgia

OBJECTIVE: To evaluate and describe the epidemiologic characteristics of Kawasaki syndrome (KS) hospitalizations in Georgia. DESIGN: We reviewed hospital discharge data and corresponding medical records for Georgian patients discharged with a KS diagnosis during 1997 and 1998. RESULTS: During the study period, 233 KS hospital discharges were recorded in Georgia; 177 (76%) were for children younger than 5 years. Twenty-one (9%) of 233 of the hospital discharges represented multiple hospitalizations. Medical records for 211 KS discharges (91%), representing 197 patients (93%), were reviewed. For those 189 patients whose medical records were reviewed and had sufficient information, 139 (74%) either had a documented illness that met the Centers for Disease Control and Prevention (CDC) definition for KS (n = 135) or had coronary artery abnormalities without meeting the CDC definition for KS (atypical KS; n = 4). Eight patients had only a history of KS. Excluding multiple hospitalizations and patients with only a history of KS, 158 hospitalizations were for patients younger than 5 years (14.0 per 100 000 children); 110 of these patients met the KS or atypical KS definition (9.8 per 100 000 children). CONCLUSIONS: Hospital discharge data are useful for KS surveillance. However, analysis of hospital discharge data may slightly overestimate the KS hospitalization rates because some discharges may represent multiple hospitalizations or hospitalizations of patients with only a history of KS. The incidence and epidemiology of KS in Georgia are consistent with findings from other continental US studies. Physicians should exercise their best clinical judgment in identifying and treating patients with KS who may not meet standard case definitions.     

Spatial and temporal clustering of Kawasaki syndrome cases

BACKGROUND: The etiology of Kawasaki syndrome (KS) remains unknown despite 30 years of intensive search for an agent. Epidemiologic clues to a possible infectious etiology include the seasonal distribution of cases, the previous occurrence of epidemics, the clinical features of the syndrome that mimic other infectious rash/fever illnesses in children, the self-limited nature of the illness, and the peak age incidence in the toddler years. METHODS: We examined the epidemiology and spatial and temporal distribution of KS cases in San Diego County, California during the 6-year period from 1998 to 2003. Clustering in space and time was analyzed using geo-referenced data with the K-function, the local G-statistic, and Knox statistic. RESULTS: A total of 318 patients were identified through active surveillance. The overall annual incidence was 21.7/100,000 in children <5 years, with rates in whites, white Hispanics, and Asian/Pacific Islanders of 15.3, 20.2, and 45.9/100,000, respectively. The Knox test showed significant clustering of cases within the space-time interval of 3 km and 3-5 days. CONCLUSIONS: This is the first study of KS cases to use geo-referenced point pattern analysis to detect spatial and temporal clustering of KS cases. These data suggest that an infectious agent triggers the immunologic cascade of KS.     

Cardiac arrest induced by blunt trauma in children.

BACKGROUND: There is incomplete knowledge regarding the outcome of children who suffer a cardiac arrest after blunt trauma. We sought to determine mechanisms of injury, mortality, and rate of organ donation in this population of children. METHODS: Since 1984, all traumatically injured children in San Diego County, California, have been treated at San Diego Children's Hospital. This review encompasses 10,979 pediatric trauma patients evaluated from August 1, 1984 through September 30, 1996. All patients who did not meet the following two criteria were eliminated from the review: 1) a mechanism of blunt trauma, and 2) cardiopulmonary resuscitation performed by a trained medical provider prior to arriving or on arrival to the hospital. A chart review of this set of patients was undertaken to determine mechanism of injury, severity of injury, mortality, and rate of organ donation. RESULTS: In this large metropolitan county, 65 children suffered cardiac arrest following blunt trauma. Accidents involving motor vehicles were the mechanisms responsible for 80% of these injuries. The average Injury Severity Score was 50.3. Mortality was largely related to severe head injury as manifested by a mean Abbreviated Injury Score for head and neck equal to 5.9. All but one of these patients died despite resuscitation. Ninety-four percent of these children died within the first 24 hours of injury. The single survivor was discharged in a vegetative state. Solid organs were obtained from 9% of the patients. CONCLUSION: The outcome from blunt cardiac arrest in children is rapidly and nearly uniformly fatal despite resuscitation. Because severe head injuries resulting in brain death are the leading cause of mortality, a significant percentage of organ donations are obtained from these patients.     

Relationship of climate, ethnicity and socioeconomic status to Kawasaki disease in San Diego County, 1994 through 1998

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in children in the United States. By monitoring trends in patient numbers and demographics during a 5-year period, we were able to explore the relationship between climate, ethnicity, socioeconomic status and susceptibility to KD. METHODS: We conducted active surveillance for all patients hospitalized with KD in San Diego County from 1994 through 1998. Data on seasonal variation in monthly rainfall and temperature were obtained from the US Meteorological Service. Patient sex, age, date of admission and self-reported ethnicity were identified from patient medical records. Socioeconomic status was assessed on the basis of insurance status among patients hospitalized at a single institution. RESULTS: During the 5-year period there were 169 cases of KD in San Diego County. The overall annual incidence of KD in children < 5 years of age ranged from 8.0 to 15.4/100 000. KD incidence was inversely associated with average monthly temperature (r = -0.47, P < 0.001) and positively associated with average monthly precipitation (r = -0.52, P < 0.001). Asian/Pacific Islanders < 5 years of age were 2.7 times as likely and Hispanics were one-third as likely to be hospitalized for KD than children from all other ethnic groups combined. Children with private or military insurance in all ethnic groups were more likely to have a diagnosis of KD than children with government assistance or no insurance. After controlling for insurance status, only Asian/Pacific Islanders remained at increased risk (rate ratio, 2.14) for KD relative to all other ethnic groups combined. CONCLUSION: KD is a common childhood vasculitis of unknown etiology. The skewed ethnic distribution and seasonality are consistent with the hypothesis that KD is an infectious disease that is influenced by environmental and genetic factors.     

Pneumocystis is not a direct cause of sudden infant death syndrome

We compared the frequency of Pneumocystis in 126 sudden infant death syndrome (SIDS) cases with a control group of 24 infants from the San Diego SIDS/SUDC Research Project who died of accidental or inflicted injuries. Cysts were identified in 33% of SIDS cases and 29% of controls. We conclude that Pneumocystis is not a direct cause of SIDS.     

The genetics of autism

Autism is a complex, behaviorally defined, static disorder of the immature brain that is of great concern to the practicing pediatrician because of an astonishing 556% reported increase in pediatric prevalence between 1991 and 1997, to a prevalence higher than that of spina bifida, cancer, or Down syndrome. This jump is probably attributable to heightened awareness and changing diagnostic criteria rather than to new environmental influences. Autism is not a disease but a syndrome with multiple nongenetic and genetic causes. By autism (the autistic spectrum disorders [ASDs]), we mean the wide spectrum of developmental disorders characterized by impairments in 3 behavioral domains: 1) social interaction; 2) language, communication, and imaginative play; and 3) range of interests and activities. Autism corresponds in this article to pervasive developmental disorder (PDD) of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and International Classification of Diseases, Tenth Revision. Except for Rett syndrome--attributable in most affected individuals to mutations of the methyl-CpG-binding protein 2 (MeCP2) gene--the other PDD subtypes (autistic disorder, Asperger disorder, disintegrative disorder, and PDD Not Otherwise Specified [PDD-NOS]) are not linked to any particular genetic or nongenetic cause. Review of 2 major textbooks on autism and of papers published between 1961 and 2003 yields convincing evidence for multiple interacting genetic factors as the main causative determinants of autism. Epidemiologic studies indicate that environmental factors such as toxic exposures, teratogens, perinatal insults, and prenatal infections such as rubella and cytomegalovirus account for few cases. These studies fail to confirm that immunizations with the measles-mumps-rubella vaccine are responsible for the surge in autism. Epilepsy, the medical condition most highly associated with autism, has equally complex genetic/nongenetic (but mostly unknown) causes. Autism is frequent in tuberous sclerosis complex and fragile X syndrome, but these 2 disorders account for but a small minority of cases. Currently, diagnosable medical conditions, cytogenetic abnormalities, and single-gene defects (eg, tuberous sclerosis complex, fragile X syndrome, and other rare diseases) together account for <10% of cases. There is convincing evidence that "idiopathic" autism is a heritable disorder. Epidemiologic studies report an ASD prevalence of approximately 3 to 6/1000, with a male to female ratio of 3:1. This skewed ratio remains unexplained: despite the contribution of a few well characterized X-linked disorders, male-to-male transmission in a number of families rules out X-linkage as the prevailing mode of inheritance. The recurrence rate in siblings of affected children is approximately 2% to 8%, much higher than the prevalence rate in the general population but much lower than in single-gene diseases. Twin studies reported 60% concordance for classic autism in monozygotic (MZ) twins versus 0 in dizygotic (DZ) twins, the higher MZ concordance attesting to genetic inheritance as the predominant causative agent. Reevaluation for a broader autistic phenotype that included communication and social disorders increased concordance remarkably from 60% to 92% in MZ twins and from 0% to 10% in DZ pairs. This suggests that interactions between multiple genes cause "idiopathic" autism but that epigenetic factors and exposure to environmental modifiers may contribute to variable expression of autism-related traits. The identity and number of genes involved remain unknown. The wide phenotypic variability of the ASDs likely reflects the interaction of multiple genes within an individual's genome and the existence of distinct genes and gene combinations among those affected. There are 3 main approaches to identifying genetic loci, chromosomal regions likely to contain relevant genes: 1) whole genome screens, searching for linkage of autism to shared genetic markers in populations of multiplex families (families with >1 affected family member; 2) cytogenetic studies that may guide molecular studies by pointing to relevant inherited or de novo chromosomal abnormalities in affected individuals and their families; and 3) evaluation of candidate genes known to affect brain development in these significantly linked regions or, alternatively, linkage of candidate genes selected a priori because of their presumptive contribution to the pathogenesis of autism. Data from whole-genome screens in multiplex families suggest interactions of at least 10 genes in the causation of autism. Thus far, a putative speech and language region at 7q31-q33 seems most strongly linked to autism, with linkages to multiple other loci under investigation. Cytogenetic abnormalities at the 15q11-q13 locus are fairly frequent in people with autism, and a "chromosome 15 phenotype" was described in individuals with chromosome 15 duplications. Among other candidate genes are the FOXP2, RAY1/ST7, IMMP2L, and RELN genes at 7q22-q33 and the GABA(A) receptor subunit and UBE3A genes on chromosome 15q11-q13. Variant alleles of the serotonin transporter gene (5-HTT) on 17q11-q12 are more frequent in individuals with autism than in nonautistic populations. In addition, animal models and linkage data from genome screens implicate the oxytocin receptor at 3p25-p26. Most pediatricians will have 1 or more children with this disorder in their practices. They must diagnose ASD expeditiously because early intervention increases its effectiveness. Children with dysmorphic features, congenital anomalies, mental retardation, or family members with developmental disorders are those most likely to benefit from extensive medical testing and genetic consultation. The yield of testing is much less in high-functioning children with a normal appearance and IQ and moderate social and language impairments. Genetic counseling justifies testing, but until autism genes are identified and their functions are understood, prenatal diagnosis will exist only for the rare cases ascribable to single-gene defects or overt chromosomal abnormalities. Parents who wish to have more children must be told of their increased statistical risk. It is crucial for pediatricians to try to involve families with multiple affected members in formal research projects, as family studies are key to unraveling the causes and pathogenesis of autism. Parents need to understand that they and their affected children are the only available sources for identifying and studying the elusive genes responsible for autism. Future clinically useful insights and potential medications depend on identifying these genes and elucidating the influences of their products on brain development and physiology.     

The risk of celiac disease in 107 families with at least two affected siblings

OBJECTIVES: Screening for celiac disease (CD) in the apparently healthy members of 107 nuclear families with two affected siblings (sib pair) and estimating the risk of CD in siblings and parents. METHODS: One hundred seven families from Sweden and southern Norway with at least two affected children were investigated. Frozen sera from 187 of the 192 healthy parents and from 94 of 95 siblings without diagnosed CD were examined for total immunoglobulin A (IgA) and anti-endomysial antibodies (EMA). Individuals with positive antibody titers underwent small intestinal biopsy. RESULTS: Positive test for EMA was found in 6 of 94 (6.3%) siblings without previously diagnosed CD and in 8 of 189 (4.2%) parents. CD was confirmed by small intestinal biopsy in all siblings and seven parents. The estimated risk for CD in multiply affected families was 26.3% for siblings and 12.9% for parents. An unexpected male preponderance was found among the new CD cases (10 males, 3 females). CONCLUSION: The risk of CD in the members of nuclear families with two affected children is approximately three times higher than that when only one child is affected. The high male preponderance of new cases is unexpected and could not be explained fully by more silent disease in males as compared with females. Considering the high level of knowledge about CD in these families, the number of undiagnosed cases is surprisingly high. The authors suggest that serologic screening should be offered to all first-degree relatives of patients with CD.     

Infant sleep position: associated maternal and infant factors.

OBJECTIVE: To determine the maternal and infant characteristics associated with the back sleep position for infants to guide efforts to increase its use and reduce the risk of Sudden Infant Death Syndrome. METHODS: Cross-sectional survey of 3349 mothers delivering in California, February-May 1999. RESULTS: Fifty-two percent of infants were placed in the back sleep position. Factors associated with a lower likelihood of using the back position included all levels of maternal education less than college (eg, for education eighth grade or less--adjusted odds ratio [OR] 0.59; 95% confidence interval [CI], 0.40-0.86); income at or below federal poverty level (OR, 0.65; 95% CI, 0.47-0.90); multiparity (OR, 0.80; 95% CI, 0.67-0.95); race/ethnicity African American (OR, 0.49; 95% CI, 0.37-0.65) and Asian/Pacific Islander (OR, 0.65; 95% CI, 0.48-0.89); speaking a non-English language (OR, 0.69; 95% CI, 0.55, 0.86); and infant age over 7 months (OR, 0.70, 95% CI, 0.52-0.96). Women in Los Angeles (OR, 0.57; 95% CI, 0.42-0.77) and urban areas other than San Diego (OR, 0.70; 95% CI, 0.53-0.92) were less likely to use the back position than those in San Francisco. CONCLUSIONS: Greater efforts are needed to promote the back sleep position among families with mothers who lack education beyond some college; live in poverty; and who are African American, Asian/Pacific Islander, multiparous, or non-English speaking.     

Risk status at discharge and cause of death for postneonatal infant deaths: a total population study

OBJECTIVES: To obtain population-based, clinical information regarding potentially modifiable factors contributing to death during the postneonatal period (28 to 364 days), we examined all postneonatal infant deaths in four areas of the United States to determine: (1) the cause of death from clinical and autopsy data rather than vital statistics, (2) whether death occurred during initial hospitalization or after discharge, and (3) the portion of postneonatal mortality attributable to infants who left the hospital with identified high-risk medical conditions. DESIGN AND SETTING: Retrospective medical record review of all postneonatal infant deaths with birth weights greater than 500 g (total N = 386) born to mothers residing in: (1) the city of Boston (1984 and 1985, N = 55), (2) the city of St Louis and contiguous areas (1985 and 1986, N = 123), (3) San Diego County (1985, N = 112), and (4) the state of Maine (1984 and 1985, N = 96). Deaths were identified using linked birth and death vital statistics, and medical record audits of infants' and mothers' charts were performed. Causes of death were obtained from medical record review in conjunction with autopsy if performed (72%, N = 278), medical record alone (17%, N = 67), or vital statistics if no other source was available (11%, N = 41). The medical conditions at the time of discharge for each infant were reviewed and, if judged to confer an increased risk of morbidity or mortality, were classified as high risk. RESULTS: The causes of death were sudden infant death syndrome (47%, N = 181), congenital conditions (20%, N = 77), prematurity-related conditions (11%, N = 43), infections (9%, N = 34), external causes (including injuries, drownings, ingestions, and burns) (7%, N = 25), and other (6%, N = 23). In 24% of congenital and 25% to 44% of prematurity-related deaths, infection was the acute or associated cause of death. Infants born to black mothers were more likely than those born to white mothers to die during the postneonatal period of all major causes of death (7.3 per 1000 vs 3.0 per 1000). Overall, 18% (N = 68) of deaths occurred to infants who never left the hospital; 79% (N = 305) of the infants were discharged before death; and discharge status was unknown in 3% (N = 13). Eighty-one percent of all infants with prematurity-related postneonatal deaths were never discharged, and of the total infants who were initially discharged, only 1% (N = 4) subsequently died of prematurity-related causes. Of all postneonatal deaths, only 16% (N = 62) left the hospital with identified high-risk medical conditions. CONCLUSIONS: These findings suggest that the etiology of postneonatal mortality is heterogeneous, with significant complexity in attributing specific causes of death and making designations of "preventability." The vast majority of infants who died of prematurity-related postneonatal causes never left the hospital, and only a small percentage of all infants that left the hospital before death were identified as being at high medical risk. Therefore, strategies for further decreasing postneonatal mortality must link high-risk follow-up programs to more comprehensive strategies that address risk throughout pregnancy and early childhood.     

Kawasaki syndrome in Denmark

OBJECTIVE: To describe the epidemiologic characteristics of Kawasaki syndrome (KS) and to estimate national KS incidence rates among children in Denmark. METHODS: A retrospective population-based study using hospital discharge records with a KS diagnosis for children younger than 15 years selected from the Danish National Hospital Register for 1981-2004. Incidence rates were calculated using the number of KS patients and corresponding census data. RESULTS: During 1981-2004, 360 children younger than 15 years were hospitalized with KS in Denmark, with 73% younger than 5 years. In this age group, the average annual incidence of KS gradually increased from 1981 to 1999 and thereafter stabilized at 4.5 to 5.0 per 100,000 person-years. The incidence was greater for boys than for girls (RR = 1.6, 95% CI = 1.2-2.0) and was highest among infants younger than 1 year (4.5), declining with increasing age (P = 0.03). However, the age-specific decline in incidence was only observed for boys, whereas the incidence for girls remained unchanged by age. The median length of hospital stay was 12 days, and the incidence peaked in the winter months. CONCLUSIONS: Major epidemiologic characteristics identified among Danish childhood KS are consistent with those described in previous studies, such as highest incidence among young children and winter-seasonality. The KS incidence rate among children younger than 5 years in Denmark increased steadily during the early study period (coinciding with global recognition of KS) and seems to have stabilized from 1998-1999 onwards. Although the incidence among Danish children was lower than that reported for several other European countries, differences in methodology challenge definite comparisons.     

Children's visits to providers of complementary and alternative medicine in San Diego.

OBJECTIVE: Increased attention has been focused on the growing use of complementary and alternative medicine (CAM); however, few studies have included children in the general US population. The present study investigated children's visits to CAM providers and factors associated with these visits. METHODS: Analysis of cross-sectional data from the 2001 United Way Outcomes and Community Impact Program telephone survey, a representative sample of households in San Diego County, California. We selected households with children younger than 19 years of age (N = 1104). Parents reported on children's CAM visits in the past year. RESULTS: Approximately 23% of parents reported that their child saw a CAM provider in the past 12 months. CAM care was sought for sick and routine care. Children of white parents had greater odds of having a CAM visit in the past year compared with children whose parents were Hispanic (adjusted odds ratio 1.71, 95% confidence interval [95% CI] 1.11-2.63). Children whose parents were college graduates had a greater likelihood of seeing a CAM provider than children of parents with high school education (adjusted odds ratio = 1.82, 95% CI 1.19-2.79). Children who were insured were also more likely to have CAM visits than uninsured children (adjusted odds ratio = 2.32, 95% CI 1.04-5.21). CONCLUSIONS: Visits to CAM providers were much more common among children in the general San Diego population compared with 1996 national estimates. Pediatric health care providers should remain aware that their patients may be using CAM so they can provide coordinated care.     

病灶多变的家族性部分性癫(癎)家系的临床研究

目的 探讨病灶多变的家族性部分性癫(FPEVF)家系的临床特征.方法 收集2008-2010年就诊于本院小儿神经专科门诊的2个FPEVF家系资料,建立家系系谱图,对先证者家系成员的临床特征、脑电图(EEG)、头颅MRI等进行总结分析.结果 1.FPEVF 2个家系共48名成员,存活44名,受累患者达21例(1例死亡).男12例,女9例;平均发病年龄5岁,起病年龄:家系A:1～7岁,家系B:2～10岁.2.发作前无明显诱发因素,白天夜间均有发作,临床表现为单纯部分性发作10例,复杂部分性发作6例,局灶继发全面性发作3例,亚临床发作2例,其中1例伴热性惊厥史.3.EEG检查19例,均有样放电,表现为频发尖波、棘波、尖慢波或棘慢波,其中起源于颞区、额颞区各5例,额区、额顶区各4例,颞枕区1例.4.存活患者20例的神经系统检查均正常,1例双侧海马异常,余MRI均正常.5.自行缓解6例,2例先证者经丙戊酸钠、托吡酯治疗,发作和EEG均有明显改善.结论 1.FPEVF是一种少见的家族性部分性癫综合征,呈常染色体不完全显性遗传,昼夜均可发作,临床多见部分性发作.2.具有明显的表型异质性和遗传异质性,临床易误诊为其他家族性部分性癫,家族史调查是诊断FPEVF的关键.3.不同家系成员脑电图部分性样放电起源于不同脑区,多见于额颞区,且大脑结构无异常.     

Survival and dominant transmission of "lethal" platyspondylic dwarfism of the "West coast" types

Torrance, San Diego, and Luton types ("West coast" types) of neonatal platyspondylic short-limbed dwarfism are suspected to be caused by dominant mutations that are obligatorily lethal. We report on an affected mother, who passed the disease to her daughter, confirming dominant disease transmission. Survival of the mother indicates a wider phenotypic spectrum.     

Survey of psychological support for bereaved families in Japan

Background:  The aim of the present study was to investigate the current conditions of psychological support for the families of children who died suddenly of disease or accident.
Methods:  A questionnaire survey was conducted in 2415 medical facilities across the country that have at least 100 beds and are staffed by pediatricians. Of these, 981 facilities (40.6%) responded to the questionnaire.
Results:  There were 653 infant deaths soon after admission in 254 facilities (25.9%). For pronouncement of death, approximately 43% of the pediatricians made no attempt to provide psychological support for the family members affected. In contrast, some 53% of the pediatricians did offer psychological support. In self-assessments, approximately 53% of the pediatricians stated that the support was 'not very satisfactory' or 'unsatisfactory', while only 28% considered that they were 'fully satisfied with the help being given'. Reasons for this response were appropriate specialized knowledge, and enough time for such tasks. The proportion of institutions that employed staff specializing in psychological support for families was only 7%. Approximately 83% of institutions without such specialist staff, however, acknowledged the need for them. The number of medical facilities that gave information regarding family support associations to bereaved families was very low (11%).
Conclusion:  Psychological support for families of children who died shortly after entering hospital cannot be characterized as satisfactory. The provision of grief care by family associations is desirable, and the cooperation of the institutions and family associations is important.     

Family studies in fetal phenytoin exposure

Sixty-two families with fetal diphenylhydantoin exposure were studied during two or more pregnancies. In 15 of these families at least one of the exposed children had some of the physical effects of DPH exposure ("affected" families); in the remaining 47 families no exposed child was affected ("unaffected" families). Review of 62 family histories and pedigrees was not helpful in differentiating these two groups for counseling purposes. However, mothers who had one affected child appeared to be at much higher risk for having subsequent affected children (9 of 10) if phenytoin use was continued through future pregnancies than were mothers whose first-born child was unaffected despite being exposed to phenytoin during the pregnancy (5 of 52 among all families, or 1 of 48 when only children exposed throughout the entire pregnancy were included). The difference between families with the first exposed child affected and first exposed child unaffected was highly statistically significant (p less than 0.0001). School and learning problems and developmental or mental retardation were present in both groups, and significantly more frequently in affected families. Physical and growth abnormalities were noted in both affected and unaffected family groups, also at a significantly higher rate in affected families.     

遗传性长QT间期综合征KCNQ1基因的新突变

目的　研究遗传性长QT间期综合征 (longQTsyndrome ,LQTS)的临床特点并筛查KCNQ1基因突变。方法　首先按照国际公认的诊断标准 ,确立先证者 ,进行家系调查 ,共有 6个LQTS家系被纳入研究。另选 50名心电图正常且校正QT间期 (QTc)≤ 0 41s的健康人作为正常基因对照。分析先证者及家系成员的临床和心电图资料 ,采用聚合酶链反应 单链构像多态性 (polymerasechainreaction singlestrandconformationalpolymorphism ,PCR SSCP)方法 ,对KCNQ1基因编码区全部序列进行基因突变筛查。阳性结果行DNA测序以明确具体突变位点 ,并进行对照研究。结果　 6个家系中共有LQTS患儿 13例 ,男 5例 ,女 8例。其中 ,猝死 1例 ( 8% ) ;晕厥发作 10例 ( 77% ) ;无症状 2例 ( 15% ) ,分别在家系调查和基因筛查时被发现。共采集到 11例患儿的心电图 ,QT间期为 ( 0 460± 0 0 58)s ,QTc为 ( 0 516± 0 0 58)s。经基因检测发现KCNQ1基因上 2个新的致病性突变位点 3 56 3 57ΔQQ和 62 6 63 1ΔGSGGPP ,分别来自 2个家系。还发现 1个新的多态性位点P448R。此 3个位点均位于编码蛋白C 末端结构域。结论　该研究发现KCNQ1基因的 2个新缺失突变位点和 1个新的多态性位点 ,系国内外首次报道 ,丰富了LQTS离子通道突变的基因库资料     

Referral and Resource Utilization Among Food Insecure Families Identified in a Pediatric Medical Setting

ObjectiveDespite increased routine screening for food insecurity (FI) in pediatric medical settings, the uptake of offered food resources after FI identification is not well understood. We aimed to 1) describe utilization of referral and supplemental resources and 2) identify characteristics associated with utilization.MethodsWe linked hospital screening and Electronic Medical Record data to Hunger Free Colorado (HFC) referral data for patients 0 to 18 years who were screened in the emergency department (ED), inpatient, or outpatient setting from January 2017 to December 2018. Among FI families, we compared patient demographic and clinical variables based on acceptance of HFC referral and connection to a food resource using Pearson's chi-square, Wilcoxon rank sum, and Poisson regression.ResultsOf 1952 patients with FI, 371 (19%) accepted a referral to HFC and of these 228 (61%) were connected to a food resource. In adjusted analyses, families screened in the ED (adjusted relative risks [aRR] 1.96, confidence interval [CI]: 1.57–2.44) and inpatient (aRR 1.74, CI: 1.20–2.53) settings more often pursued referral to HFC than those screened in Child Health Clinic, while those screened in Special Care Clinic less often pursued referral (aRR 0.24, CI: 0.14–0.41). Families with 3 or more people in the home were more likely to be connected to resources (aRR 2.67, CI: 1.42–5.04).ConclusionsOnly a small proportion of families with FI identified in a medical setting are ultimately connected to food resources. Higher rates of HFC referral among ED and inpatient families suggest that increased screening efforts in these settings may be warranted.     

Partial biotinidase deficiency: clinical and biochemical features

Neonatal screening for profound biotinidase deficiency (less than 10% of the mean normal activity level) has identified a group of children with partial biotinidase deficiency (10% to 30% of mean normal activity). Because partial biotinidase deficiency may result in clinical consequences that may be prevented by treatment with biotin, we evaluated such individuals and their family members (1) to determine whether partial biotinidase deficiency is associated with symptoms and (2) to determine the inheritance pattern. We quantified serum biotinidase activity levels and obtained medical histories of probands, their parents and siblings, and additional family members. All children with partial deficiency were healthy at the time of diagnosis. One child, who was not initially treated with biotin, later developed hypotonia, hair loss, and skin rash, which resolved with biotin therapy. Four adults and three children with partial biotinidase deficiency were identified among family members of infants identified by neonatal screening. All these individuals were healthy, although one sibling had elevated urinary lactate excretion. A fifth adult with partial deficiency, found among clinically normal adult volunteers, later showed minor symptoms that resolved after biotin therapy. Like children with profound biotinidase deficiency, children with partial biotinidase deficiency are symptoms free at birth. However, the subsequent occurrence of symptoms of profound biotinidase deficiency in some persons with partial deficiency suggests that biotin therapy for this condition may be warranted.