[Show abstract][Hide abstract] ABSTRACT: 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-1β, 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.
Journal of the American Society of Nephrology 11/2011; 22(11):2047-56. · 8.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a 12-year-old boy with osteoblastic osteosarcoma of the right femur. He was started on chemotherapy according to the EURAMOS/COSS 1 protocol. Chemotherapy with doxorubicin/cisplatin resulted in reversible acute renal failure and methotrexate levels were repeatedly elevated. Family history suggested an autosomal dominant polycystic kidney disease. Genetic testing revealed a novel mutation c.10707_10712del (p.Val3569_3570del) in exon 36 of the PKD1 gene. Patients with autosomal dominant polycystic kidney disease may be at risk for acute renal failure during chemotherapy without signs of renal impairment. A careful family history is important to exclude risk factors for renal impairment before introducing high-dose chemotherapy.
Journal of Pediatric Hematology/Oncology 10/2010; 32(8):e314-6. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Exposure to inorganic mercury (Hg) is a serious problem presenting with a combination of neurological and psychiatric symptoms along with weight loss, pruritus, erythema, arterial hypertension, tachycardia, and renal tubular dysfunction. We report a 4-year-old girl with chronic intoxication of inorganic mercury secondary to the accidental use of an Hg₂Cl₂- and HgCl₂-containing skin whitening cream (urine level of Hg, 41.1 μg/l; reference level, < 25 μg/l). Under treatment with dimercapto-1-propansulficacid, Hg level in the urine raised to 1,175.5 μg/l, neurological deterioration occurred, and brain magnetic resonance imaging (MRI) showed on fluid attenuated inversion recovery sequences new hyperintense lesions in the subcortical white matter. After 4 months, clinical signs and symptoms and brain MRI findings resolved. This is a first case of inorganic mercury poisoning showing hyperintense lesions in brain MRI and confirms earlier cases showing transient deterioration during chelation therapy. Although urinary excretion could be enhanced during chelation therapy, signs and symptoms of intoxication could be worsened.
European Journal of Pediatrics 10/2010; 170(6):747-50. · 1.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thin basement membrane nephropathy (TBMN) and Alport syndrome (ATS) are genetically heterogeneous conditions characterized by structural abnormalities in the glomerular basement membrane (GBM). TBMN presents with hematuria, minimal proteinuria, and normal renal function. Although TBMN is an autosomal dominant disease (COL4A3 and COL4A4), ATS can be inherited X-linked (COL4A5), autosomal recessive, or autosomal dominant (both COL4A3 and COL4A4). The clinical course of TBMN is usually benign, whereas ATS typically results in end-stage renal disease (ESRD). Nevertheless, there is a broad spectrum of clinical phenotypes caused by mutations in COL4A3 or COL4A4. We report an Italian family who presented with hematuria and mild proteinuria. Mutational analysis showed a novel heterozygous mutation p.G291E in exon 15 of the COL4A3 gene. Many different mutations in COL4A3 and COL4A4 that cause TBMN have already been identified, but most genetic variability in these genes has been found to cause autosomal ATS. A valid genotype-phenotype correlation for TBMN or ATS is not yet known. Therefore, it is important to identify new mutations by direct sequencing to clarify their clinical importance, to assess the prognosis of the disease, and to avoid renal biopsy.
[Show abstract][Hide abstract] ABSTRACT: A 6-month-old male infant presented with failure to thrive. Hypernatraemia and elevated serum osmolality in the presence of low urine sodium and osmolality led to the diagnosis of diabetes insipidus. Administration of 1-deamino-8-D-arginine vasopressin (dDAVP) neither decreased urine volume nor increased urine osmolality indicating congenital nephrogenic diabetes insipidus. Molecular analysis in the arginine-vasopressin receptor-2 gene ( AVPR2 ) located on chromosome Xq28 demonstrated a novel 5-base pair deletion (c.962–966delACCCC; g.1429–1433delACCCC) leading to a shift of the reading frame (p.Asn321fs) and a premature termination codon implying an absent or non-functional protein. Treatment with hydrochlorothiazide, amiloride and indomethacin led to a favourable clinical course.
[Show abstract][Hide abstract] ABSTRACT: The occurrence of Brachyspira species and Lawsonia intracellularis was investigated by PCR analyses of faeces from 60 children living on European pig farms. In addition, 60 other children were included as controls. Two samples were positive for B. aalborgi but B. pilosicoli and L. intracellularis were not demonstrated.
Epidemiology and Infection 09/2007; 135(6):1043-5. · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In recent years, studies have shown a protective effect of being raised in a farm environment on the development of hay fever and atopic sensitization. Inconsistent data on the relation of farming to asthma and wheeze have raised some doubt about a true protective effect.
We sought to study the differential effects of farm-associated exposures on specific asthma-related health outcomes.
The cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle study included 8263 school-age children from rural areas in 5 European countries. Information on farm-related exposures and health outcomes was obtained by using questionnaires. In subsamples allergen-specific IgE and RNA expression of CD14 and Toll-like receptor genes were measured, and dust from children's mattresses was evaluated for microbial components.
Inverse relations with a diagnosis of asthma were found for pig keeping (odds ratio [OR], 0.57; 95% CI, 0.38-0.86), farm milk consumption (OR, 0.77; 95% CI, 0.60-0.99), frequent stay in animal sheds (OR, 0.71; 95% CI, 0.54-0.95), child's involvement in haying (OR, 0.56; 95% CI, 0.38-0.81), and use of silage (OR, 0.55; 95% CI, 0.31-0.98; for nonatopic asthma) and in Germany for agriculture (OR, 0.34; 95% CI, 0.22-0.53). Protective factors were related with higher expression levels of genes of the innate immunity. Potential risk factors for asthma and wheeze were also identified in the farm milieu. Levels of endotoxin and extracellular polysaccharides were related to the health outcomes independently of the farm exposures.
The protective effect of being raised in a farm environment was ascribed to distinct exposures.
The development of atopic sensitization and atopic and nonatopic asthma is most likely determined by different environmental factors, possibly reflecting distinct pathomechanisms.
Journal of Allergy and Clinical Immunology 06/2007; 119(5):1140-7. · 12.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cases of foreign bodies in the bladder self-inserted via urethra are not rare in childhood. Urinary tract infection, dysuria, lower abdominal pain, or haematuria with and without pain are common symptoms. We report on a 11-year-old boy with accidentally detected microscopic haematuria, proteinuria and leukocyturia. Because of increasing proteinuria up to 2330 mg/g creatinine and elevated antistreptolysin titre glomerulonephritis was suspected. However, some echogenic material was detected in the bladder by ultrasound. X-ray of the pelvis showed a 30 cm long tube projecting onto the bladder. The boy then admitted having had inserted a plastic tube into the urethra two years ago. The foreign body was removed cystoscopically. Four weeks after cystoscopy erythrocyturia, leucoyturia and proteinuria had disappeared. We state that symptoms of a local inflammation caused by a foreign body in the bladder can imitate the symptoms of nephritis.
[Show abstract][Hide abstract] ABSTRACT: In children with nocturnal bedwetting, the basic diagnostic evaluation to differentiate between monosymptomatic enuresis and organic or functional urinary incontinence is mandatory. When the diagnosis of monosymptomatic enuresis is set, a stepped therapeutic program is available, in which alarm/behavior therapy has a central role. Drug therapy of monosymptomatic enuresis in childhood is an established option and is reserved for certain indications.
MMW Fortschritte der Medizin 03/2007; 149(5):42-5.
[Show abstract][Hide abstract] ABSTRACT: Dust collection by study participants instead of fieldworkers would be a practical and cost-effective alternative in large-scale population studies estimating exposure to indoor allergens and microbial agents. We aimed to compare dust weights and biological agent levels in house dust samples taken by study participants with nylon socks, with those in samples taken by fieldworkers using the sampling nozzle of the Allergology Laboratory Copenhagen (ALK). In homes of 216 children, parents and fieldworkers collected house dust within the same year. Dust samples were analyzed for levels of allergens, endotoxin, (1-->3)-beta-D-glucans and fungal extracellular polysaccharides (EPS). Socks appeared to yield less dust from mattresses at relatively low dust amounts and more dust at high dust amounts than ALK samples. Correlations between the methods ranged from 0.47-0.64 for microbial agents and 0.64-0.87 for mite and pet allergens. Cat allergen levels were two-fold lower and endotoxin levels three-fold higher in socks than in ALK samples. Levels of allergens and microbial agents in sock samples taken by study participants are moderately to highly correlated to levels in ALK samples taken by fieldworkers. Absolute levels may differ, probably because of differences in the method rather than in the person who performed the sampling. Practical Implications Dust collection by participants is a reliable and practical option for allergen and microbial agent exposure assessment. Absolute levels of biological agents are not (always) comparable between studies using different dust collection methods, even when expressed per gram dust, because of potential differences in particle-size constitution of the collected dust.
Indoor Air 01/2007; 16(6):414-25. · 3.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nephronophthise (NPH), eine autosomal-rezessiv vererbte zystische Nierenerkrankung, ist die häufigste genetische Ursache für chronisches Nierenversagen bei Kindern und jungen Erwachsenen und kann mit extrarenalen Manifestationen assoziiert sein. Sie ist gekennzeichnet durch die histologische Trias von Desintegration der tubulären Basalmembran, tubulärer Atrophie mit Entwicklung von Zysten und interstitieller Zellinfiltration mit Fibrose. In den vergangenen Jahren konnten enorme Fortschritte im Verständnis der molekularen Grundlagen der NPH gemacht werden. Es ist erwiesen, dass NPH sowohl durch klinische wie auch durch genetische Heterogenität gekennzeichnet ist. Inzwischen konnten sechs für die NPH verantwortliche Gene identifiziert werden.
[Show abstract][Hide abstract] ABSTRACT: There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role.
We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring.
In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toll-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information.
Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% CI, 1.04-1.2), and 1.10 (95% CI, 1.03-1.23), respectively.
Maternal exposure to an environment rich in microbial compounds might protect against the development of atopic sensitization and lead to upregulation of receptors of the innate immune system. The underlying mechanisms potentially operating through the intrauterine milieu or epigenetic inheritance await further elucidation.
When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.
Journal of Allergy and Clinical Immunology 05/2006; 117(4):817-23. · 12.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevalence of allergic diseases has increased rapidly in recent decades, particularly in children. For adequate prevention it is important not only to identify risk factors, but also possible protective factors. The aim of this study was to compare the prevalence of allergic diseases and sensitization between farm children, children in anthroposophic families, and reference children, with the aim to identify factors that may protect against allergic disease.
The study was of cross-sectional design and included 14,893 children, aged 5-13 years, from farm families, anthroposophic families (recruited from Steiner schools) and reference children in Austria, Germany, The Netherlands, Sweden and Switzerland. A detailed questionnaire was completed and allergen-specific IgE was measured in blood.
Growing up on a farm was found to have a protective effect against all outcomes studied, both self-reported, such as rhinoconjunctivitis, wheezing, atopic eczema and asthma and sensitization (allergen specific IgE > or = 0.35 kU/l). The adjusted odds ratio (OR) for current rhinoconjunctivitis symptoms was 0.50 (95% confidence interval (CI) 0.38-0.65) and for atopic sensitization 0.53 (95% CI 0.42-0.67) for the farm children compared to their references. The prevalence of allergic symptoms and sensitization was also lower among Steiner school children compared to reference children, but the difference was less pronounced and not as consistent between countries, adjusted OR for current rhinoconjunctivitis symptoms was 0.69 (95% CI 0.56-0.86) and for atopic sensitization 0.73 (95% CI 0.58-0.92).
This study indicates that growing up on a farm, and to a lesser extent leading an anthroposophic life style may confer protection from both sensitization and allergic diseases in childhood.
[Show abstract][Hide abstract] ABSTRACT: Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. This might be related to increased inhalatory exposure to microbial agents.
To assess the association between microbial agents in house dust and atopic wheeze in farm children, Steiner school children and reference children.
Levels of bacterial endotoxin, fungal beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in mattress and living room floor dust were measured in a population of 270 atopic (=Phadiatop-positive) children with self-reported wheezing, including 168 current atopic wheezers, and 441 non-atopic, non-symptomatic controls. These children were selected from a cross-sectional study in five European countries.
In the study population as a whole, average levels of mattress dust endotoxin, EPS and glucans were slightly (1.1-1.2-fold; P<0.10) higher in control children than in atopic wheezers. Atopic wheeze was related to mattress levels of endotoxin, EPS and glucans in farm and farm-reference children. However, when adjusting for group (farm vs. farm-reference children), the associations became non-significant whereas the group effect remained. No associations between atopic wheeze and microbial agents were observed in Steiner and Steiner-reference children. For current atopic wheeze, the farm effect became non-significant after adjustment for microbial agent levels.
Not only bacterial endotoxin but also mould components might offer some protection against atopic wheeze in children. However, the protective effect of being raised on a farm was largely unexplained by the mattress microbial agent levels measured in this study.
[Show abstract][Hide abstract] ABSTRACT: In most epidemiological surveys the estimated prevalence of asthma is based on questionnaire responses, which may depend on the individual's perception as well as medical consulting habits in a given population. Therefore, measurement of bronchial hyper-responsiveness as a key feature of asthma has been suggested as an objective parameter for asthma.
The aim of the present study was to validate questionnaire responses on asthma and wheeze against bronchial response to hypertonic saline (HS) (4.5%) in populations previously shown to have a lower prevalence of asthma and allergies: farmers' children and children from anthroposophic families.
Children whose parents had completed a written questionnaire in the cross-sectional PARSIFAL-study were drawn from the following four subgroups: 'farm children' (n=183), 'farm reference children' (n=173), 'Steiner schoolchildren' (n=243) and 'Steiner reference children' (n=179). Overall, 319 children with wheeze in the last 12 months and 459 children without wheeze in the last 12 months performed an HS challenge.
Odds ratios, sensitivity, specificity, likelihood ratios and measures of association did not differ significantly between the four subgroups. The correlation between the bronchial response to HS and wheeze and asthma questions was moderate and similar for farm children, farm reference children, Steiner schoolchildren and Steiner reference children (kappa for 'wheeze': 0.25, 0.33, 0.31, 0.35, respectively, P=0.754, kappa for 'doctor's diagnosis of asthma': 0.33, 0.19, 0.33, 032, respectively, P=0.499).
The findings from this study suggest that the reliabilitiy of questionnaire responses on asthma and wheeze is comparable between farmers' children, children raised in families with anthroposophic lifestyle and their respective peers.
[Show abstract][Hide abstract] ABSTRACT: Ein akutes dialysepflichtiges Nierenversagen im Kindesalter wird in etwa 6% der Flle durch Glomerulopathien verursacht. Hufig ist eine intensivmedizinische Behandlung erforderlich, insbesondere wenn sekundre Organkomplikationen aufgetreten sind. Diese zeigen oft eine vorwiegend neurologische Symptomatik und erfordern eine dringliche Diagnostik und Therapie. Neben dem relativ hufigen hmolytisch-urmischen Syndrom kann eine Vielfalt von Glomerulopathien zum akuten Nierenversagen fhren. Bei einigen dieser Erkrankungen kann bei frhzeitiger Diagnosestellung durch aggressive Therapie zumindest die Langzeitprognose verbessert werden. Beim Krankheitsbild der rapid progressiven Glomerulonephritis sind dazu in letzter Zeit bei erwachsenen Patienten therapeutische Fortschritte erzielt worden, die auch fr die Pdiatrie relevant sein knnten. Der Einsatz spezieller Blutreinigungsverfahren wie Plasmapherese oder Immunadsorption bei Kindern wird in dieser Arbeit ebenfalls diskutiert.Acute renal failure is caused by glomerulopathies in about 6% of paediatric cases. Patients often have to be admitted to the intensive care unit, especially when there is secondary organ involvement. The symptoms that develop are mainly neurological, demanding rapid diagnosis and treatment. There are various glomerulopathies besides haemolytic-uraemic syndrome, which is encountered relatively often, that can lead to acute renal failure. In some of these, the long-term prognosis at least can be significantly improved by rapid diagnosis and aggressive treatment. In the case of rapidly progressive glomerulonephritis there have been recent advances in treatment in adult medicine, which may also prove applicable in pediatric patients. The use of more specific blood purification procedures, such as plasmapheresis or immunoadsorption, in children is also discussed.