Fetal endoscopic myelomeningocele closure preserves segmental neurological function.

AIM: Our aim was to compare the effect of prenatal endoscopic with postnatal myelomeningocele closure (fetally operated spina bifida aperta [fSBA]) versus neonatally operated spina bifida aperta [nSBA]) on segmental neurological leg condition. METHOD: Between 2003 and 2009, the fetal surgical team (Department of Obstetrics, University of Bonn, Germany) performed 19 fetal endoscopic procedures. Three procedures resulted in fetal death, three procedures were interrupted by iatrogenic hemorrhages and 13 procedures were successful. We matched each successfully treated fSBA infant with another nSBA infant of the same age and level of lesion, resulting in 13 matched pairs (mean age 14 mo; SD 16 mo; f/m=1.6; female-16, male-10). Matched fSBA and nSBA pairs were compared in terms of segmental neurological function and leg muscle ultrasound density (MUD). We also determined intraindividual difference in MUD (dMUD) between myotomes caudal and cranial to the myelomeningocele (reflecting neuromuscular damage by the myelomeningocele) and compared dMUD between fSBA and nSBA infants. Finally, we correlated dMUD with segmental neurological function. RESULTS: We found that, on average, the fSBA group were born at a lower gestational age than the nSBA group (median 32 wks [range 25-34 wks] vs 39 wks [34-41 wks]; p=0.001) and experienced more complications (chorioamnionitis, premature rupture of the amniotic membranes, oligohydramnios, and infant respiratory distress syndrome necessitating intermittent positive-pressure ventilation). Neurological function was better preserved after fSBA than after nSBA (median motor and sensory gain of two segments; better preserved knee-jerk [p=0.006] and anal [p=0.032] reflexes). The dMUD was smaller in fSBA than in nSBA infants (mean difference 24, 95% confidence interval [CI] 15-33; p<0.05), which was associated with better preserved segmental muscle function. INTERPRETATION: Fetal endoscopic surgery is associated with spinal segmental neuroprotection, but it results in more complications. Before considering clinical implementation of fetal endoscopic myelomeningocele closure as standard care, the frequency of complications should be appropriately reduced and results assessed in larger groups over a longer period of time.

Mutations in multiple PKD genes may explain early and severe polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is typically a late-onset disease caused by mutations in PKD1 or PKD2, but about 2% of patients with ADPKD show an early and severe phenotype that can be clinically indistinguishable from autosomal recessive polycystic kidney disease (ARPKD). The high recurrence risk in pedigrees with early and severe PKD strongly suggests a common familial modifying background, but the mechanisms underlying the extensive phenotypic variability observed among affected family members remain unknown. Here, we describe severely affected patients with PKD who carry, in addition to their expected familial germ-line defect, additional mutations in PKD genes, including HNF-1ß, which likely aggravate the phenotype. Our findings are consistent with a common pathogenesis and dosage theory for PKD and may propose a general concept for the modification of disease expression in other so-called monogenic disorders.

Does human bocavirus infection depend on helper viruses? A challenging case report.

A case of severe diarrhoea associated with synergistic human bocavirus type 1 (HBoV) and human herpes virus type 6 (HHV6) is reported. The case supports the hypotheses that HBoV infection under clinical conditions may depend on helper viruses, or that HBoV replicates by a mechanism that is atypical for parvoviruses, or that HBoV infection can be specifically treated with cidofovir.

Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis.

BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by Staphylococcus aureus abscesses, recurrent pneumonia, increased serum IgE levels, and eczema. The association of heterozygous signal transducer and activator of transcription 3 (STAT3) mutations with autosomal dominant (AD)-HIES allows the differentiation of AD-HIES from disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis. OBJECTIVE: To facilitate early diagnosis of AD-HIES to initiate appropriate therapy. METHODS: The clinical phenotype (suggested by a National Institutes of Health [NIH] score of >or=40 points), STAT3 genotype, and T(H)17 cell counts were compared in a cohort of 78 patients suspected of having HIES. RESULTS: Heterozygous STAT3 missense mutations and in-frame deletions were identified in 48 patients, all but 2 with an NIH score >or=40 points. Patients with STAT3 mutations with HIES showed significantly lower T(H)17 cell counts compared with patients with wild-type STAT3 and control subjects. Only 1 patient with wild-type STAT3 had both an NIH score >or=40 points and abnormal T(H)17 cell counts (

Levels of mobility in children and adolescents with spina bifida-clinical parameters predicting mobility and maintenance of these skills.

PURPOSE: The retrospective study was performed to apply the "Hoffer criteria" as a suitable classification of mobility in spina bifida patients. We looked at clinical parameters and factors that can be used as predictors for future mobility and development in these patients. MATERIALS AND METHODS: Clinical data about ambulation of 90 spina bifida/myelomeningocele patients were collected using a questionnaire and were completed using the medical records of the patients. The patients were grouped by their walking distances according to "Hoffers criteria" (community walker, household walker, exercise walker, nonwalker). The development of the mobility skills over the years was documented. RESULTS: We grouped 42% of the patients as community walkers, 16% as household, 16% as exercise walkers, and 27% as always wheelchair dependent (nonwalker). We found significant correlations between the Hoffer criteria, the level of lesion the walking distance and the ability to stand upright. There is also a significant relation between the Hoffer criteria and the frequency of fractures and the age of the patients. The occurrence of fractures is directly related to the level of lesion and to the level of mobility in our group of patients. Of all our patients, 39% patients had improved in mobility, 37% patients retained their achieved state, and 24% worsened in their mobility skills. CONCLUSIONS: We could see that a stable and ambitious milieu and care in specialized institutions can achieve a high level of ambulation in spina bifida patients. Most patients are able to maintain this skill over a long period of time. Predictive factors to maintain mobility in patients with myelomeningoceles (spina bifida) are not only dependent on the level of lesion but also rely on the aftercare of the patients too. The data that were collected are used for counseling of parents and patients.

HLA-DQ8 and the HLA-DQ8-DR4 haplotype are positively associated with the hevein-specific IgE immune response in health care workers with latex allergy.

BACKGROUND: Hevein is one of the most important latex allergens affecting health care workers (HCWs). OBJECTIVE: Because the genetically determined susceptibility is one important factor regulating type I allergy, the association between the hevein-specific IgE immune response and HLA class II alleles of DQB1 and DRB1, DRB3, DRB4, and DRB5 was studied. METHODS: The distribution of HLA-DQB1 and DRB1, DRB3, DRB4, and DRB5 in 269 HCWs with latex allergy, 56 latex-sensitized patients with spina bifida (SB), and 90 nonatopic control subjects under special consideration for hevein-specific IgE was examined. RESULTS: Seventy percent (189/269) of the HCWs with latex allergy and 39% (22/56) of the latex-sensitized patients with SB had increased hevein-specific IgE antibody concentrations (>0.35 kU/L). HLA data analysis revealed significantly increased phenotype frequencies for DQB1*0302 (DQ8; 91/189 [48%]) and DRB1*04 (DR4; 102/189 [54%]) in hevein-positive HCWs with latex allergy compared with the 80 hevein-negative HCWs with latex allergy (DQB1*0302: 16/80 [20%], corrected P value [P (c)] = 7.1 x 10(-4); DRB1*04: 23/80 [29%], P (c) =.01) and with control subjects (DQB1*0302: 16/89 [18%], P (c) = 1 x 10(-4); DRB1*04: 22/90 [24%], P (c) = 3.2 x 10(-4)). The DQ8-DR4 haplotype frequency was significantly elevated in HCWs with hevein-specific IgE antibodies when compared with that in HCWs without hevein-specific IgE antibodies (47% vs 18%, P (c) = 5.3 x 10(-4)) or control subjects (47% vs 18%, P (c) = 9.6 x 10(-4)). In contrast, latex-sensitized patients with SB with hevein-specific IgE antibodies showed an increased but not significant DQB1*0302 frequency (7/22 [32%] vs 2/34 [6%], P =.02, P (c) = not significant) compared with that seen in those without hevein-specific IgE antibodies. CONCLUSION: The DQB1*0302 (DQ8) alone, the DQB1*0302 (DQ8)-DRB1*04 (DR4) haplotype, or both are significantly involved in the hevein-specific IgE immune response in HCWs with latex allergy.