Familial testicular torsion in three consecutive generations of first-degree relatives

We report the first and largest family with testicular torsion in three consecutive generations affecting four first-degree relatives. The incidence of familial testicular torsion is under reported in the literature. We recommend eliciting family history in evaluation of acute scrotum, as a useful adjunct for clinical decision making. In families with a strong predisposition to testicular torsion, management should include family counseling about the significant risk of occurrence of this condition.     

Islet autoantibodies and insulin dependent diabetes mellitus in cystic fibrosis

Cystic fibrosis-related diabetes mellitus (CF-DM) is thought to be secondary to beta-cell destruction by fibrous tissue replacing the exocrine pancreas. The aim of this study was to investigate the hypothesis that other factors may also be responsible. Glutamic acid decarboxylase (GAD) and islet cell (IA-2) antibodies were measured by quantitative ELISA in a group of patients with CF (n=30) in comparison to a group of newly diagnosed DM type 1 (IDDM) patients (n=30) and normal subjects (n=30). GAD antibodies were positive (>32 ng/ml) in 50% of the CF, 93% of the IDDM and 0% of the control group. IA-2 antibodies were detected (>0.9 U/ml) in 40% of the CF, 93% of the IDDM and 0% of the control group. Among the fifteen CF patients with positive GAD and IA-2 antibodies, four already had IDDM and another five abnormally low (<45 mU/l) first phase insulin response (FPIR) indicating a prediabetic state. We conclude that factors other than mechanical may be involved in the development of CFDM. The presence of autoantibodies predicting IDDM supports the hypothesis that CF-DM may have a multifactorial pathogenesis.     

Sleep-disordered breathing and upper-airway anomalies in first-degree relatives of ALTE children.

From 1985 through 1995, 348 infants aged 3 wk-3 mo were referred to the Stanford Sleep Clinic for "apparent life-threatening events" (ALTE). A small group of 48 infants with no history of sleep-disordered breathing (SDB) was also recruited and used as controls (they comprised group C). We conducted a systematic investigation of relatives (parents, siblings, and grandparents) of the infants, including a clinical evaluation, craniofacial investigation, and the completion of an extensive (189-question) validated sleep/wake questionnaire. All data were calculated before the subdivision of ALTE infants into two groups. The subdivision was based on a blind scoring of the infants' polygraphic recordings; 42.5% of the infants were negative for SDB (Group A), whereas 57.5% of the infants were positive for SDB (Group B). Groups A and C were not significantly different from each other. Forty-three percent of the relatives of Group B infants had been treated for SDB (with nasal CPAP, surgical or dental appliance treatments) compared with 7.1% of Group A relatives. Clinical investigation indicated a significantly higher presence of small upper airways in the families of infants with SDB. About twice as many relatives reported the presence of asthma in Group B compared with Group A. Naso-oro-maxillomandibular anatomic traits that may lead to small upper airways in parents may be risk factors for abnormal breathing during sleep in their infants.     

Progression to first-degree heart block in preschool children exposed in utero to maternal anti-SSA/Ro52 autoantibodies

Aims: To study the children exposed in utero to maternal anti‐SSA/Ro52 antibodies in terms of impaired atrioventricular (AV) conduction or disturbed myocardial performance, and to investigate the ability of prenatal Doppler to predict conduction abnormalities during childhood. Methods: Fifty‐seven children exposed in utero to anti‐SSA/Ro52 antibodies were grouped in accordance with (A) prolonged AV time intervals in utero by Doppler or (B) normal findings and examined by ECG, 24‐hour ECG and echocardiography. Results: PR interval on ECG was longer in group A (n = 16) compared with that of group B (n = 41), 140 ± 24 ms vs. 121 ± 13 ms (p < 0.01). Six cases of 1°Atrioventricular block (AVB) developed in group A, giving an estimated prevalence of 10.5%, (95% confidence interval; 4.4–22.2%), progressing from normal sinus rhythm at 1 month of age. Prenatal Doppler predicted development of 1°AVB at follow‐up with a sensitivity of 100%, Positive predictive value (PPV) 37.5%, LR+ 5.1, and Negative predictive value (NPV) 100%. Children in group A had a slightly higher myocardial performance index in flow and tissue Doppler imaging recordings. Conclusions: Ten per cent of children exposed in utero to anti‐SSA/Ro52, with a normal ECG at birth or 1 month of age, progressed to 1°AVB during preschool years. Cases at risk can be identified by prenatal Doppler echocardiography.     

Increased prevalence of autoimmune diseases in first-degree relatives of patients with celiac disease

BACKGROUND: The prevalence of autoimmune disorders is increased in patients with celiac disease (CD), and it is unknown whether their first-degree relatives also have a high risk of autoimmune disorders. METHODS: To assess the prevalence of autoimmune diseases in first-degree relatives of CD patients, the authors looked for autoimmune disorders in 225 first-degree relatives of 66 children with CD (group A) and in 232 first-degree relatives of 68 healthy children (group B). For both groups, serologic screening for CD was performed through antiendomysium (EMA) and tissue transglutaminase autoantibodies (tTGAA). EMA- and tTGAA-positive subjects were offered an intestinal biopsy. The age at onset of autoimmune diseases was also recorded in group A. RESULTS: The prevalence of autoimmune disorders was significantly (P = 0.028) higher in group A (11 of 225, 4.8%) than in group B (2 of 232, 0.86%). In relatives of CD patients, the prevalence increased with age (chi2 for trend, 43.5; P < 0.0001). Serologic screening for CD was only positive in group A (15 of 225 subjects). An intestinal biopsy was performed in 13 of these 15 relatives (2 refused biopsy). Eleven of 13 had flat mucosa, with subclinical or silent forms of CD. The prevalence of autoimmune diseases in the EMA- and tTGAA-positive relatives of CD patients was significantly higher (3 of 15, 20%; P = 0.028; odds ratio, 6.3; 95% CI, 1/0.21-1/0.11, 4.9-7.6) than in those who were EMA and tTGAA negative (8/210, 3.8%). CONCLUSIONS: The first-degree relatives of CD patients have an increased risk of autoimmune diseases, most likely connected with unrecognized subclinical or silent forms of CD.     

EB-virus-specific IgM and IgG antibodies in first-degree relatives of children with acute lymphoblastic leukaemia.

EB-virus-specific IgM and IgG antibodies (to virus capsid and soluble complement fixing antigens) were estimated in sera from mothers and sibs of children with acute lymphoblastic leukaemia, from patients with infectious mononucleosis, and from control induviduals. IgM antibodies were present in 12 of 16 mothers and 3 of 4 sibs of children with acute lymphoblastic leukaemia. They were also present in 14 of 16 patients with infectious mononucleosis, but in only 1 of 12 control individuals.     

Islet cell transplantation in children

This paper aims to provide an overview of islet cell transplantation in children, with specific attention to pediatric total pancreatectomy with islet autotransplantation (TPIAT). We will summarize the definition and causes of chronic pancreatitis in children, the TPIAT procedure and potential complications, the process of islet cell isolation and autotransplantation, and long-term results after TPIAT. Lastly, we will briefly discuss islet cell allotransplantation in the adult population and its potential role in treating children.     

Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders

OBJECTIVE: Etiologically unexplained disorders of language and social development have often been reported to improve in patients treated with immune-modulating regimens. Here we determined the frequency of autoantibodies to brain among such children. DESIGN: We collected sera from a cohort of children with (1) pure Landau-Kleffner syndrome (n = 2), (2) Landau-Kleffner syndrome variant (LKSV, n = 11), and (3) autistic spectrum disorder (ASD, n = 11). None had received immune-modulating treatment before the serum sample was obtained. Control sera (n = 71) were from 29 healthy children, 22 with non-neurologic illnesses (NNIs), and 20 children with other neurologic disorders (ONDs). We identified brain autoantibodies by immunostaining of human temporal cortex and antinuclear autoantibodies using commercially available kits. RESULTS: IgG anti-brain autoantibodies were present in 45% of sera from children with LKSV, 27% with ASD, and 10% with ONDs compared with 2% from healthy children and control children with NNIs. IgM autoantibodies were present in 36% of sera from children with ASD, 9% with LKSV, and 15% with ONDs compared with 0% of control sera. Labeling studies identified one antigenic target to be endothelial cells. Antinuclear antibodies with titers >/=1:80 were more common in children with ASD and control children with ONDs. CONCLUSION: Children with LKSV and ASD have a greater frequency of serum antibodies to brain endothelial cells and to nuclei than children with NNIs or healthy children. The presence of these antibodies raises the possibility that autoimmunity plays a role in the pathogenesis of language and social developmental abnormalities in a subset of children with these disorders.     

Cytoplasmic islet cell antibodies remain valuable in defining risk of progression to type 1 diabetes in subjects with other islet autoantibodies

The discovery of islet cell antibodies (ICAs) was the prelude to the understanding that type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease. The issue regarding whether or not the measurement of ICAs should be completely replaced by biochemical markers detecting islet autoantibodies (AAs) for the prediction of T1DM has been the subject of endless international debates. In light of this controversy, we assessed the current role of ICAs as a predictive marker for T1DM progression. We examined a cohort of 1484 first-degree relatives (FDRs) of T1DM probands from the Children's Hospital of Pittsburgh Registry. These relatives were consecutively enrolled between 1979 through 1984 and followed up to 22 yr. Serum obtained at the time of enrollment was assayed for ICAs, glutamic acid decarboxylase (GAD)65, insulin A (IA)-2 AA, and insulin AAs (IAAs). In FDRs who had ICAs in addition to GAD65 and IA-2 AAs, the cumulative risk of developing insulin-requiring diabetes was 80% at 6.7 yr of follow-up, whereas this risk in those with GAD65 and IA-2 AAs without ICAs was only 14% at 10 yr of follow-up (log rank: P < 0.00001). Cox regression analysis showed that diabetes risk was significantly associated with the presence of ICAs in both subjects with low titer and high titer GAD65 and IA-2 AAs. The addition of IAAs in GAD65 and IA-2 AA-positive relatives did not increase the cumulative risk for conversion to insulin-treated diabetes. We provide evidence that a subgroup of ICAs predicts a more rapid progression to insulin-requiring diabetes in GAD65 and IA-2 AA-positive relatives and should remain part of the assessment of T1DM risk for intervention trials. In addition, these findings provide impetus for efforts to identify a novel islet autoantigen(s) reactive with this ICA subset.     

Prevalence of coeliac disease in diabetic children and their first-degree relatives in West Algeria: screening with serological markers

Atypical and relatively silent forms of coeliac disease (CD) have been described in insulin-dependent diabetes mellitus (IDDM). Our aim was to evaluate the prevalence of CD-IDDM with serological markers and to investigate the presence of CD in the IDDM first-degree relatives. During 1993 94 we explored 116 IDDM patients reported as new cases and 381 first-degree relatives of IDDM patients. Determination of IgA and IgG antigliadin antibodies (AGA) and IgA antiendomysium antibodies (AEA) was made. Jejunal biopsy was performed in symptomatic patients or in those with positive serological markers, (i) Nineteen IDDM-CD were identified and 5 were suspected. Thus, the prevalence of CD in IDDM patients was between 16.4 and 20%. AGA and/or AEA were abnormal in 13 and normal in 5. Sensitivity was 80% for the three tests when used simultaneously and specificity was 100%. (ii) In the family study, 26 sera of asymptomatic first-degree relatives of IDDM patients were positive for at least one of the serological markers; 13 of them had villous atrophy. Systematic serological screening in IDDM allowed us to detect CD and evaluate the true incidence.     

Environmental factors related to the induction of beta-cell autoantibodies in 1-yr-old healthy children

We studied environmental risk factors which might contribute to the development of beta-cell autoantibodies in healthy children. Here, we investigated 6000 randomly selected children from the large All Babies in Southeast Sweden (ABIS) cohort, including 17 055 newborns recruited between 1997 and 1999. Questionnaires at birth and at 1 yr of age and the levels of autoantibodies to glutamic acid decarboxylase (GADA) and autoantibodies to tyrosine phosphatase (IA-2A) at 1 yr of age were analyzed. The 99th percentile cutoff for autoantibodies was proposed to identify children at risk of type 1 diabetes (T1D) and the 90th percentile cutoff to identify children in whom beta-cell autoimmunity has been induced. Using the 90th percentile cutoff level, 1156 children had either IA-2A (n = 574) or GADA (n = 582), while 126 children had both GADA and IA-2A. When the 99th percentile cutoff level was used, 114 children had either IA-2A (n = 57) or GADA (n = 57), and six children had both GADA and IA-2A. In logistic regression analysis, celiac disease in grandparents [odds ratio (OR) 2.2] and maternal gastrointestinal infection (OR 1.1) represented a risk for simultaneous occurrence of both IA-2A and GADA above the 90th percentile. Birth in spring (March to May) (OR 1.5) and male gender (OR 1.3) were risk factors for induction of IA-2A. Mother's low education represented a risk for induction of IA-2A (OR 1.5) and GADA (OR 1.4). T1D in first-degree relatives increased the risk for beta-cell autoimmunity above the 99th percentile (OR 2.6), whereas type 2 diabetes in grandparents was associated with GADA (OR 2.1). Exposure to cow's milk formulas <2 months of age implied an OR of 2.9 for IA-2A above the 99th percentile.