Is glycogen storage disease 1a associated with atherosclerosis?

Deficiency of microsomal glucose-6-phosphatase in liver and kidney leads to glycogen storage disease type la (GSD 1a). Notwithstanding intensive dietary therapy, moderate to severe dyslipidaemia and microal-buminuria, both known atherosclerotic risk factors, remain present. Although more patients reach adult age, no information is still available about accelerated athero-sclerosis. the aim of our study was to investigate whether GSD 1a was associated with premature atherosclerosis. In nine adolescent patients (mean age 22.7±3.4 years) and nine matched healthy control subjects, lipid profile, blood pressure, ankle-brachial indices, aortic distensibility and intima-media thickness (IMT) of the carotid and femoral arteries were determined. As expected, lipid profiles were significantly unfavourable in the patient group compared with the control group. No differences were found in blood pressure, ankle-brachial indices and aortic distensibility between both groups. IMT segments were comparable in both groups, with even thinner segments in the patient group. In different multivariate models, GSD la remained an independent predictor for a thinner IMT (R²=0.90; \=−0.69;P=0.018).Conclusion: glycogen storage disease type 1a is not associated with premature atherosclerosis, despite the existence of longstanding dyslipidaemia and microalbuminuria. Published online: 2 July 2002     

Disseminated nontuberculous mycobacterial infection in a child with interferon-γ receptor 1 deficiency

We describe the case of a 2-year-old boy with disseminated infection by a rapidly growing, poorly pathogenic mycobacterial species that belonged to the Mycobacterium fortuitum–Mycobacterium peregrinum complex. He had a severe course characterized by a poor response to treatment and recurrent lymph node abscess formation. Sequencing of the interferon-γ receptor 1 gene (IFNγR1) revealed that he was homozygous for a novel null mutation, 453delT. Patients presenting with disseminated infections by rapidly growing environmental mycobacteria must be investigated for complete IFNγR1 deficiency. The spectrum of IFNγR1 genotypes associated with this immunological disorder is expanding.     

Absence of breast-feeding is associated with the risk of type 1 diabetes: a case–control study in a population with rapidly increasing incidence

There are indications that the effect of environmental factors on the risk of type 1 diabetes mellitus (T1DM) is increasing over time. This can be documented by the rapid increase of T1DM incidence in genetically stable populations. Our aim was to study an association of T1DM with the variable factors of the perinatal period and of early infancy, using data from children born over a period of changing exposure to some of the studied factors. A case–control dataset was analysed, consisting of 868 diabetic children and 1,466 anonymous controls, mostly schoolmates of the children with T1DM. The data were collected using structured questionnaires completed by parents. After performing univariate analyses, the associations were analysed using multiple logistic regression adjusted for potential confounders, including the year of birth. The risk of T1DM decreased with increasing duration of breast-feeding, while no breast-feeding was associated with an increased T1DM risk, OR=1.93 [95% CI: 1.33–2.80], breast-feeding for more than 12 months was protective, OR=0.42 [95% CI: 0.22–0.81], both being relative to the reference category of breast-feeding for 1–3 months. A short duration of day-care attendance (none or less than 1 year) was weakly associated with the risk of T1DM, OR=1.65 [95% CI: 1.05–2.62]. No association was detected between T1DM and signs of prenatal infections, perinatal stress factors, birth size and weight, indicators of crowding or the presence of a domestic pet in the household. Short breast-feeding period and short attendance to day care is associated with the risk of T1DM in Czech children.     

Pelger-Huët anomaly in a child with 1q42.3-44 deletion

Congenital Pelger–Huët anomaly (PHA) is an autosomal dominant disorder characterized by hypolobulated neutrophils with coarse clumping of the nuclear chromatin. PHA has been recently linked to the gene encoding the lamin B receptor, located at chromosome 1q41‐43. The authors report a case of PHA in a child with interstitial deletion of the 1q subtelomeric region (1q42.3‐44), providing supportive evidence to this linkage. All neutrophils in the peripheral blood smear had the characteristic unsegmented or bilobed appearance. Additional features in this child included failure to thrive, developmental delay, cleft palate, seizure disorder, and dysmorphic facial features. © 2005 Wiley‐Liss, Inc.     

The Pallister-Killian syndrome in a child with rare karyotype—a diagnostic problem

The Pallister-Killian syndrome is a clinically recognizable syndrome, usually due to a tissue-specific mosaicism for a 12p isochromosome [i(12p)]. We report a rare case of Pallister-Killian syndrome with 12p mosaicism, tetrasomy/trisomy/disomy in fibroblasts and trisomy/disomy in lymphocytes. Marker chromosomes were investigated with conventional cytogenetic techniques and fluorescent in situ hybridisation (FISH). The karyotype was established as: mos47,XX,+12p/47,XX,+i(12p)/46,XX. The cytogenetic result of the extra mosaic 12p presented in lymphocytes suggested the diagnosis of trisomy 12p, although, in combination with clinical manifestations, the Pallister-Killian syndrome was considered and confirmed by the cytogenetic analysis of fibroblasts.     

A “flipped” kidney in utero in an infant with a double collecting system and a Gartner's duct cyst with a vaginal ectopic ureter

We report an infant with two unique anatomic abnormalities. A flipped kidney in utero is described with the association of a Gartner's duct cyst and a vaginal ectopic ureter with a duplicated collecting system.     

Magnetic resonance cystography with gadopenetate dimeglumine of a cystic craniopharyngioma in a child – a technical note

Large cystic craniopharyngiomas can be treated with chemotherapy injected directly into the cyst. Chemotherapy is toxic if it leaks from the cyst into the subarachnoid space. We present a child with a cystic craniopharyngioma following surgical placement of a catheter into the cystic component. Computed tomography following iodinated contrast injection into the cyst was inconclusive in determining the cyst wall integrity. Magnetic resonance following dilute gadopentetate dimeglumine injection into the cyst clearly defined a leak into the subarachnoid space. Coronal imaging was especially helpful. This technique is simple to perform and useful for clinical management. Received: 23 April 1999/Accepted: 24 May 1999     

“Milky” urine—a child with chyluria

A 10-year-old boy with chyluria due to a congenital fistulous communication between the lymphatic system and the bladder is described. Chyluria can be parasitic or non-parasitic. Many causes of non-parasitic chyluria have been reported. Lymphography is the pre-operative imaging procedure of choice since it demonstrates the site, the calibre and the number of the fistulous communications. Lymphoscintigraphy shows very well the site of the fistula but is not as precise as lymphography. However, it has the advantage to be less invasive and is an excellent alternative in the non-surgical cases. The prognosis of non-parasitic chyluria is usually very good and the treatment is mostly conservative.     

Alström-syndrome: a missed diagnosis with consequences

BACKGROUND: Alstr?m-syndrome (OMIM: 203 800) is a rare disease with autosomal recessive inheritance. Characteristic features are retinal degeneration, truncal obesity, diabetes mellitus and sensorineural hearing loss. Further variable symptoms include chronic hepatitis and asthma. CASE REPORT: A patient with asthma associated with retinal degeneration is presented. The investigations demonstrated truncated obesity, sensorineural deafness and impaired glucose tolerance and Alstrom-syndrome was diagnosed. She received hearing aids, diabetes training and is regularly reinvestigated for further manifestations of Alstr?m-syndrome.     

How to Proceed with Examination of a Child?

The assessment of a child is quite different from that of adults and requires knowledge of normal variations in anatomy and physiology with growth and development. An important part of initial assessment includes triage and recognizing children with emergency signs so that they can be managed at the earliest to prevent death and referred timely to the specialist. After ruling out emergency signs, the children with priority signs require prompt assessment, management and referral to the specialist. In addition to normal history as in adults, prenatal and birth history, developmental history, immunization history, feeding history and social history are important for complete assessment of the child. The approach to physical examination should consider age and developmental level. It is important to make the child comfortable with pleasant surroundings and playful behavior to yield maximum information from the examination. In addition to diagnosing disease, pediatric assessment should involve identification of malnutrition, immunization status, level of development, screening for 4 Ds (Defects at birth, Deficiencies, Diseases and Developmental Delay including Disability), hearing and visual assessment and detection of child abuse. Tanner staging and psychosocial assessment should be done in adolescents.     

Booster vaccination and 1-year follow-up of 4–8-year-old children with a reduced-antigen-content dTpa-IPV vaccine

Reduced-antigen-content pertussis vaccines designed initially for booster vaccination of adolescents and adults can also be used to vaccinate pre-school age children. Combination vaccines, which reduce the number of administered injections, combine multiple antigens including inactivated poliovirus (IPV), which is recommended in this age group in some countries. This randomised, controlled study compared a combined diphtheria-tetanus-acellular pertussis-inactivated polio-containing booster vaccine, dTpa-IPV (Boostrix™ Polio, n = 822), to separately administered dTpa (Boostrix™) and IPV (IPV Mérieux™, n = 136) in 4–8-year-old children who had previously received four doses of DTPa. Additional serological assessment was performed 1 year after the booster dose. One month after vaccination, seroprotection/vaccine response rates were similar for both groups. At least 99.9% of the subjects had protective antibodies against diphtheria, tetanus and polio, and at least 90.1% had a vaccine response to pertussis antigens after dTpa-IPV. Reactogenicity of dTpa-IPV was comparable to dTpa + IPV. Fever and grade 3 loss of appetite occurred more commonly after dTpa-IPV, whereas swelling and grade 3 pain occurred more frequently after separately administered dTpa + IPV (P < 0.05 for all). However, 95% CIs overlapped in all cases. Large swelling reactions after dTpa-IPV occurred less commonly than have been reported after a fifth dose of DTPa. One year after the booster, 98.6% of the subjects tested continued to have protective antibodies against diphtheria, tetanus and polio, and at least 81.2% were seropositive for pertussis components. The reduced-antigen-content dTpa-IPV vaccine was immunogenic, well tolerated and safe in pre-school age children. It provides immunity against four diseases in a single injection, with the potential reactogenicity benefit of a reduced-antigen dose. Source of financial support: GlaxoSmithKline Biologicals, Rixensart, Belgium.     

Refractory anemia with ringed sideroblasts in children: two diseases with a similar phenotype?

Three pediatric patients with refractory anemia with ringed sideroblasts (RARS) are presented. Bone marrow aspirates were examined using Romanowsky and Prussian blue iron stains in all three patients, and electron microscopic analysis was performed in one patient. All three patients had cytogenetic analysis of the bone marrow. Other studies included analysis of serum iron, total iron-binding capacity, ferritin, copper, vitamins B6 and B12, and folate levels. Antibody titers to Parvovirus, HIV, and other viruses were measured. The patients had contrasting clinical courses. Patients 1 and 2 had dysplastic hematopoietic features and cytogenetic findings (with either partial or one allele loss of chromosome 7), suggestive of myelodysplastic syndrome. Patient 1 experienced acute myeloid leukemia (AML) and had a good response to AML-directed therapy. Patient 2 had prolonged cytopenias and underwent bone marrow transplantation (BMT). Patient 3 had features suggestive of refractory anemia associated with mitochondrial cytopathy, including normal cytogenetics with pronounced vacuolization of marrow precursors. His anemia regressed spontaneously a few months after diagnosis. These patients represent two subgroups of pediatric RARS. Patients with the myelodysplastic syndrome (MDS) type may progress to cytopenias or leukemia and may require aggressive therapy; the type is characterized by clonal cytogenetic findings. The non-MDS type, which may relate to mitochondrial cytopathy, often shows spontaneous regression and requires only supportive treatment; it has normal cytogenetic findings.     

Hyperzincemia with systemic inflammation: a heritable disorder of calprotectin metabolism with rheumatic manifestations?

A boy had infantile-onset systemic inflammation, growth failure, hepatosplenomegaly, anemia, leukocytopenia, progressive muscular dystrophy, and hypercalprotectinemia, resulting in marked hyperzincemia. His mother had a history of chronic arthritis since childhood and also showed hypercalprotectinemia/hyperzincemia. We postulate an inherent defect in calprotectin metabolism.     

Elastase inhibitory activity of airway α1-antitrypsin is protected by treatment with a catalytic antioxidant in a baboon model of severe bronchopulmonary dysplasia

Recent studies in animal models of bronchopulmonary dysplasia (BPD) suggest that antioxidant treatments may be beneficial for the disease. However, the mechanisms by which these drugs improve the course of BPD are not completely known. Alpha1-antitrypsin (α1-AT) is one of the major serine protease inhibitors in human plasma that has antielastase and antiapoptotic activities. Both activities of α1-AT are dependent on its reactive site loop (RSL), which is highly susceptible to oxidative inactivation. In this study, we investigated the elastase inhibitory activity of α1-AT in two different baboon models of BPD, the "new BPD" and the "severe BPD" models, and determined the effect of treatment with a catalytic antioxidant, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP), on the elastase inhibitory activity of α1-AT in the severe BPD model. Our results demonstrate the presence of sufficient elastase inhibitory activity of the airway α1-AT in the new but not in the severe BPD model. Treatment of severe BPD group baboons with the catalytic antioxidant MnTE-2-PyP resulted in augmentation of the elastase inhibitory activity of α1-AT. These findings suggest that prevention of the oxidative inactivation of α1-AT may be one of the mechanisms by which antioxidant therapy improves the pulmonary outcomes in animal models of severe BPD.     

COL1a1 COL3a1在发育性髋脱位患儿关节囊的表达

目的：发育性髋脱位（developmental dislocation of the hip, DDH）的病因目前不明,但其与髋关节松弛密切相关。该研究通过比较DDH患儿与正常儿童关节囊中Ⅰ,Ⅲ型胶原在mRNA及蛋白水平的表达差异, 以探索DDH患儿髋关节松弛的原因。方法：选取性别相同年龄相近的9对发育性髋脱位患者及正常儿童配对比较。采用半定量RT-PCR及Western-Blot法检测COL1a1 COL3a1在mRNA及蛋白水平的表达。图像分析软件进行量化分析,并经统计学处理。结果：COL1a1在DDH组mRNA及蛋白水平表达均较正常对照组降低(P0.05)。结论： DDH患儿关节囊中 Ⅰ 型胶原在mRNA及蛋白水平表达较正常同性同龄儿降低,可能是导致DDH患儿髋关节松弛的原因。DDH患儿髋关节松弛可能与 Ⅲ 型胶原含量无关。