Clinical Characteristics of Perinatal Lethal Hypophosphatasia: A Report of 6 Cases

Hypophosphatasia is a rare inherited disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. It is classified into 6 subtypes, and the perinatal lethal form of hypophosphatasia is the most severe. Patients with this form suffer from various symptoms, including respiratory failure, premature craniosynostosis, rachitic changes in the metaphyses, convulsions and hypercalcemia. This report presents 6 cases of the perinatal lethal form of hypophosphatasia. All of the patients showed shortening of the long bones in utero in ultrasonographic examinations. Two of the six patients died at birth because they could not establish spontaneous breathing. Three of the remaining four patients also died before 1 yr of age. The major cause of death was respiratory failure due to hypoplastic lung. All of the patients, except for the two who died at birth, experienced convulsions in their clinical courses. Vitamin B6 therapy effectively reduced the frequency and severity of convulsions. However, it could not always make the patients convulsion free. Three patients underwent a genetic analysis. The 1559delT mutation, which abolishes Alkaline Phosphatase (ALP) activity, was a hot spot. A homozygous 1559delT mutation was observed in two patients. However, they differed in severity of symptoms. Although a good genotype-phenotype correlation has been reported in hypophosphatasia, the genotype alone does not always predict the life span of the patients. These cases therefore suggested the importance of genetic counseling.     

Primary Antibiotic Resistance to Helicobacter pylori Strains Isolated From Children in Northern Iran: A Single Center Study

Background:

Initial resistance to antibiotics is the main reason for the failure of Helicobacter pylori (H. pylori) eradication in children.

Objectives:

As we commonly face high antibiotic resistance rates in children, we aimed to determine the susceptibility of H. pylori to common antibiotics.

Patients and Methods:

In this cross-sectional in vitro study, 169 children younger than 14 years with clinical diagnosis of peptic ulcer underwent upper gastrointestinal endoscopy. Biopsy specimens from stomach and duodenum were cultured. In isolated colonies, tests of catalase, urease, and oxidase as well as gram staining were performed. After confirming the colonies as H. pylori, the antibiogram was obtained using disk diffusion method.

Results:

Culture for H. pylori was positive in 12.3% of the specimens, urease test in 21.3%, serological test in 18.9% and stool antigen test was positive in 21.9%. We could show high specificity but moderate sensitivity of both histological and H. pylori stool antigen tests to detect H. pylori. The overall susceptibility to metronidazole was 42.9%, amoxicillin 95.2%, clarithromycin 85.7%, furazolidone 61.9%, azithromycin 81.0%, and tetracycline 76.2% with the highest resistance to metronidazole and the lowest to clarithromycin.

Conclusions:

In our region, there is high resistance of H. pylori to some antibiotics including metronidazole and furazolidone among affected children. To reduce the prevalence of this antibiotic resistance, more controlled use of antibiotics should be considered in children.     

Flixweed vs. Polyethylene Glycol in the Treatment of Childhood Functional Constipation: A Randomized Clinical Trial

Background:

Polyethylene glycol (PEG) is often considered as the first-line treatment for functional constipation in children. Descurainia sophia (L.) Webb et Berth (D. sophia) is a safe recommended medicine in Iranian folk and Traditional Persian Medicine for the treatment of constipation.

Objectives:

To clinically compare D. sophia with PEG 4000 (without electrolyte) in pediatric constipation and to assess its efficacy and side effects.

Patients and Methods:

120 patients aged 2 - 12 years with constipation for at least 3 months were included in an 8 weeks lasting randomized controlled trial within two parallel-groups. Children received either PEG, 0.4 g/kg/day, or D. sophia seeds, 2 grams (for children aged 2 - 4 years) and 3 grams (for those aged > 4 years) per day.

Results:

A total of 109 patients completed the study (56 in D. sophia and 53 in PEG group). At the end of the study, 36 (64.3%) patients in D. sophia group and 29 (54.7%) in PEG group were out of Rome III criteria (P = 0.205). Median weekly stool frequency in 0, 1, 2, 3 weeks of the treatment was found to be 2, 5, 5, 5 in D. sophia and 3, 4, 4, 5 in PEG group (P = 0.139, 0.076, 0.844, 0.294), respectively. The number of patients who suffered flatulence was less (5, 8.9%) in D. sophia group as compared to PEG group (6, 11.3%) at the end of the trial (P = 0.461). D. sophia taste was less tolerated.

Conclusions:

D. sophia is introduced as a cheap and available medication which can be applied as a safe alternative to conventional PEG in the management of pediatric chronic functional constipation.     

Staphylococcus aureus bloodstream infections in children: A population-based assessment

BACKGROUND:

Although Staphylococcus aureus is a major cause of bloodstream infections, population-based data on these infections in children are limited.

OBJECTIVE:

To describe the epidemiology of S aureus bacteremia in children.

METHODS:

Population-based surveillance for all incident S aureus bacteremias was conducted among children (18 years of age or younger) living in the Calgary Health Region (Alberta) from 2000 to 2006.

RESULTS:

During the seven-year study, 120 S aureus bloodstream infections occurred among 119 patients; 27% were nosocomial, 18% health care associated and 56% community acquired. The annual incidence was 6.5/100,000 population and 0.094/1000 live births. A total of 52% had a significant underlying condition, and this was higher for nosocomial cases. Bone and joint (40%), bacteremia without a focus (33%), and skin and soft tissue infections (15%) were the most common clinical syndromes. Infections due to methicillin-resistant S aureus were uncommon (occurring in one infection) and three patients (2.5%) died.

CONCLUSIONS:

S aureus bacteremia is an important cause of morbidity in the paediatric age group. Underlying medical conditions and implanted devices are important risk factors. Methicillin-resistant S aureus and mortality rates are low.     

A novel MC4R mutation associated with childhood-onset obesity: A case report

The melanocortin-4-receptor gene (MC4R) is a key regulator of energy homeostasis, food intake and body weight. MC4R gene mutations are associated with early-onset severe obesity. Most patients are heterozygotes, with some reports of homozygotes and compound heterozygotes. The authors report a case involving an eight-year-old girl with progressive weight gain from infancy, body mass index 44 kg/m² (>97th percentile), hyperphagia, hyperinsulinemia and increased linear growth. There was no phenotype of morbid obesity in the parents or sibling. Coding regions and intron-exon boundaries of the genes encoding leptin, leptin receptor, pro-opiomelanocortin and MC4R were analyzed. Two heterozygous coding mutations in the MCR4 gene (S94N and C293R) were detected, of which the second has not been previously reported. The mutations were on opposite chromosomes, confirming compound heterozygosity. The molecular findings and clinical features associated with this novel MC4R mutation are described. The authors emphasize that rare mutations can be found in some patients with severe childhood-onset obesity.     

A sentinel fatal paediatric case of community-associated methicillin-resistant Staphylococcus aureus in Canada

Community-associated methicillin-resistant Staphylococcus aureus is an established pathogen in many centres in the United States, but has yet to establish a firm foothold in Canada. In the present article, the authors report, to their knowledge, Canada’s first fatal paediatric case of invasive disease due to community-associated methicillin-resistant S aureus and review its pathogenesis, epidemiology and treatment.     

A Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus reuteri for Chronic Functional Abdominal Pain in Children

Background:

Functional abdominal pain (FAP) is one of the most common diseases, and large percentages of children suffer from it.

Objectives:

The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain.

Patients and Methods:

This study was a randomized double-blind placebo-controlled trial. Children aged 4 to 16 years with chronic functional abdominal pain (based on Rome III criteria) were enrolled in the study. They were randomly divided into two groups, one receiving probiotic and the other placebo.

Results:

Forty children received probiotic and forty others placebo. There were no significant differences in age, weight, sex, location of pain, associated symptoms, frequency and intensity of pain between the groups. The severity and frequency of abdominal pain in the first month compared to baseline was significantly less and at the end of the second month, there was no significant difference between both groups compared to the end of the first month.

Conclusions:

This study showed that the severity of pain was significantly reduced in both groups. There was no significant difference in pain scores between them. The effect of probiotic and placebo can probably be attributed to psychological effect of the drugs.     

Saccharomyces Boulardii in Helicobacter Pylori Eradication in Children: A Randomized Trial From Iran

Background:

Helicobacter pylori infects around 50% of the human population and is asymptomatic in 70% of the cases. H. pylori eradication in childhood will not only result in peptic symptoms relief, but will also prevent late-term complications such as cancer. Today, probiotics are being increasingly studied in the treatment of gastrointestinal infections as an alternative or complement to antibiotics.

Objectives:

In this study we aimed to assess the effect of S. boulardii supplementation on H. pylori eradication among children in our region.

Patients and Methods:

In this randomized double-blind placebo-controlled clinical trial 28 asymptomatic primary school children with a positive H. pylori stool antigen (HpSA) exam were randomly allocated into the study group, receiving Saccharomyces boulardii, and the control group receiving placebo capsules matched by shape and size, for one month. The children were followed up weekly and were reinvestigated four to eight weeks after accomplished treatment by HpSA testing. The significance level was set at P < 0.05.

Results:

24 children completed the study. The mean HpSA reduced from 0.40 ± 0.32 to 0.21 ± 0.27 in the study group, indicating a significant difference (P = 0.005). However, such difference was not observed in the control group (P = 0.89). Moreover, the HpSA titer showed a 0.019 ± 0.19 decrease in the study group whereas the same value was 0.0048 ± 0.12 for the controls, again stating a significant difference (P = 0.01).

Conclusions:

Saccharomyces boulardii has a positive effect on reducing the colonization of H. pylori in the human gastrointestinal system but is not capable of its eradication when used as single therapy.     

New Single Nucleotide Deletion In the SMPD1 Gene Causes Niemann Pick Disease Type A in a Child from Southwest Iran: A Case Report

Objective

Niemann Pick disease (NPD) type A (NPA: MIM #257200) is a lipid storage disorder with an autosomal recessive inheritance and occurrs by defect of the SMPD1 gene encoding sphingomyelinase. Disruption of this enzyme leads to the accumulation of sphingomyelin in brain and liver, which in turn causes dysfunction or damage of tissue.

Methods

We report firstly a 2.5 year old boy with NPA in southwest Iran. Initially, the diagnosis was resulted on the basis of clinical symptoms. The genomic DNA of the suspected individual was subjected to exon sequencing of the SMPD1 gene. According to the human reference sequence {"type":"entrez-nucleotide","attrs":{"text":"NM_000543.4","term_id":"300795568","term_text":"NM_000543.4"}}NM_000543.4, a novel single guanine deletion resulting in a frameshift mutation (p.Gly247Alafs*9) was observed in the SMPD1 gene that might be causative for the outcome of the disease.

Findings

The present report is the first molecular genetics diagnosis of the NPA in southwest Iran. The detected deletion in the SMPD1 gene is remarkable because of its novelty.

Conclusion

Despite similar morbidity SGA infants exhibited higher lethal complication rates following delayed meconium passage compared to AGA infants.     

From genes to vaccine: A breakthrough in the prevention of meningococcal group B disease

Although safe and effective vaccines exist for meningococcal serogroups A, C, W-135 and Y, no vaccine is available for routine use against disease caused by serogroup B (MenB). Consequently, MenB is now the most common cause of invasive meningococcal disease in Canada. MenB causes more than 80% of invasive meningococcal disease in infants and can occur at any age. The mortality and morbidity rates related to this disease are very high. Vaccine development against MenB has been hampered by the fact that MenB polysaccharide is not immunogenic in humans. Although vaccines derived from the outer membrane vesicle have been effective in controlling MenB outbreaks, such vaccines protect against the outbreak strain only. A new vaccine development strategy, reverse vaccinology, has led to the identification of genes coding for surface-exposed proteins, which are able to induce bactericidal antibodies against a broad range of MenB strains. A new vaccine containing a combination of these proteins has been tested in different age groups, in several clinical trials. The data available provide hope that control of MenB through routine vaccination will soon be possible.     

Using probiotics in the paediatric population

As more is learned about the importance of the intestinal microbiome to human health there is increasing interest in the potential benefits of probiotics. Probiotics are live micro-organisms which, when consumed in adequate amounts, confer a health effect on the host by altering its microflora. Probiotics have been administered both prophylactically and therapeutically for various conditions. This statement defines the development and role of intestinal microflora, and examines the evidence supporting the use of different probiotics to treat common paediatric conditions, such as diarrhea, atopy, functional intestinal disorders and necrotizing enterocolitis.     

Reduction in pediatric hospitalizations for varicella-related invasive group A streptococcal infections in the varicella vaccine era

OBJECTIVES: To assess changes in hospitalization rates for invasive group A streptococcal (IGAS) and varicella-associated IGAS (VA-IGAS) infections at a pediatric hospital over a period of 9 years, to characterize clinical features of patients with IGAS infections, and to assess frequency of macrolide-resistant IGAS isolates.Study design Medical records of all hospitalized patients with group A streptococcus isolated from a normally sterile site from 1993 to 2001 were reviewed. Data collected included demographics, clinical course, microbiologic features, outcome, and presence of streptococcal toxic shock syndrome (STSS) or necrotizing fasciitis (NF). Annual hospitalization rates for IGAS were determined. RESULTS: There were 144 patients with IGAS infections, including 11 (8%) with STSS or NF. Overall mortality rate was 2% (3/144) but 18% (2/11) among patients with STSS or NF. Preexisting varicella was present in 16% (23/144); 4 of 23 VA-IGAS cases had STSS or NF. Although there was no change in annual hospitalization rates for IGAS infections during the study period, the percentage of VA-IGAS hospitalizations decreased from 27% in the prevaccine era (1993 to 1995), to 16% during vaccine implementation (1996 to 1998) and 2% during widespread vaccine use (1999 to 2001) (linear-by-linear association, P=.001). Macrolide resistance was low in 1993 to 1995 (5%, 1/19) and 1996 to 1998 (0%, 0/42) among tested IGAS isolates and increased significantly in 1999 to 2001 (13%, 5/38) (Fisher exact, P=.035). CONCLUSIONS: A decline in pediatric varicella-related IGAS hospitalizations was temporally associated with utilization of varicella vaccine. These data reinforce the importance of universal varicella vaccination for children. Increasing macrolide resistance among IGAS isolates indicates a need for continued surveillance.     

Epidemiology and clinical management of tuberculosis in children in Canada

Although often regarded as a foreign disease, latent tuberculosis or tuberculosis disease will be encountered in many clinical situations by the Canadian child health practitioner. There are key differences between tuberculosis in children and adults. In the present article, the changing epidemiology of tuberculosis in children in Canada and around the world, the pathogenesis of infection, diagnostic tests, and clinical management of childhood latent tuberculosis and tuberculosis disease are reviewed.