Glucose–6–phosphate dehydrogenase deficiency in India

Glucose–6–phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance. It has been reported from India more than 30 years ago and the prevalence varies from 0–27% in different caste, ethnic and linguistic groups. The major clinical manifestations are drug induced hemolytic anemia, neonatal jaundice and chronic non–spherocytic hemolytic anemia. Individuals with G6PD deficiency have a selective advantage against falciparum malaria. Thirteen biochemically characterized variants have been reported from India. At the molecular level, G6PD Mediterranean is the most common deficient variant in the caste groups whereas, G6PD Orissa is more prevalent among the tribal of India. The third common variant seen in India is G6PD Kerala–Kalyan     

Surgical implications of the Smith–Lemli–Opitz syndrome

Smith–Lemli–Opitz syndrome (SLOS) is a syndrome of rare multiple congenital anomalies/mental retardation associated with low plasma cholesterol levels. Prior to receiving the diagnosis of SLOS, affected children may present as a neonatal surgical emergency with ambiguous genitalia, Hirschsprungs disease, and pyloric stenosis. We present two fatal cases of SLOS with near-total Hirschsprungs disease; the surgical, anaesthetic, and medical aspects of the cases are discussed, and a literature review is presented.     

Pulmonary Artery Banding Before the Damus–Kaye–Stansel Procedure

Subaortic stenosis (SAS) in a single ventricle leads to myocardial hypertrophy and compromises Fontan results. Moreover, controversy exists concerning the optimal surgical strategy for relieving SAS. We have applied pulmonary artery banding (PAB) before the Damus–Kaye–Stansel procedure (DKS), and here we analyze factors that influence systemic ventricular compliance. Thirteen patients underwent PAB before DKS. Median PAB duration was 5.5 months (range, 20 days to 17.7 months). Procedures administered concomitantly with DKS were Blalock–Taussig shunt (n = 6), bidirectional cavopulmonary shunt (n = 5), and Fontan operation (n = 2). All survived and were doing well after a median follow-up 2.7 years. Cardiac catheterization before DKS showed that the mean pressure gradient across the systemic ventricular outflow tract and PAB were 20.6 ± 10.1 and 67.4 ± 10.2 mmHg, respectively. After DKS, systemic ventricular end diastolic pressure (SVEDP) was significantly correlated with PAB duration (r = 0.65, p = 0.022), but not with PAB or systemic ventricle outflow tract pressure gradients. After DKS, SVEDP decreased or fell to within the range in patients with PAB duration less than 7 months (p < 0.05). Seven patients had a successful Fontan operation, and 6 without risk factors are waiting operation. SVEDP was found to be correlated with PAB duration, and our findings indicate that short-term PAB can be considered a safe option in patients with a single ventricle and SAS.     

Fanconi–Bickel Syndrome

We Present the first mutation proven case of Fanconi–Bickel syndrome, a rare type of glycogen storage disease, from India. A four-year-old girl presented with severe growth retardation, genu varum and hepatomegaly. Investigations confirmed severe hypophosphatemic rickets and Fanconi syndrome. Molecular analysis confirmed a homozygous deletion insertion mutation in Glut 2 gene.     

A case–control study of risk factors for severe hand–foot–mouth disease among children in Ningbo, China, 2010–2011

Background

A small fraction of hand–foot–mouth disease (HFMD) progression from the onset of severity to fatality may be remarkably rapid. Early recognition of children at risk of severity is critical to increase treatment effectiveness and reduce acute mortality.

Methods

A frequency-matched case–control study was conducted between January 2010 and June 2011 in Ningbo to identify risk factors associated with the occurrence of severity in children with HFMD. Data including demographic characteristics, clinical features, and laboratory test results were collected by trained interviewers through retrospective medical record review and/or face-to-face interviews with children’s parents using a standardized questionnaire.

Results

Eighty-nine cases with severe HFMD and 267 controls with mild HFMD were recruited in this study. Palm rashes (OR?=?0.004, 95%CI?=?0.000–0.039, p?p?p?=?0.030), leg trembling (OR?=?29.008, 95%CI?=?1.535–548.178, p?=?0.025), papule rash (OR?=?4.622, 95%CI?=?1.110–19.252, p?=?0.035), a raised WBC count?>?10.8?×?10⁹/L (OR?=?4.495, 95%CI?=?1.311–15.415, p?=?0.017), and human enterovirus 71 infection (OR?=?39.172, 95%CI?=?9.803–156.522, p?Conclusion Clinicians should pay increased attention to children diagnosed as HFMD with the independent risk factors above.     

Megacystis–microcolon–intestinal hypoperistalsis and prune belly: overlapping syndromes

Megacystis–microcolon–intestinal hypoperistalsis syndrome (MMIHS) is a rare, often fatal condition. Infants present with a functional obstruction of the gastrointestinal tract (GI), malrotation, microcolon, and a large nonobstructed bladder. Several features common to both MMIHS and Eagle–Barrett or prune belly syndrome (PBS) include hydronephrosis, bladder distension and laxity of the abdominal wall musculature. Additionally, MMIHS and PBS have been reported in the same family, suggesting the possibility of a common pathogenesis. MMIHS usually presents in female infants. We present a male infant diagnosed with both MMIHS and PBS. This is a unique case in which both MMIHS and true PBS are present in the same infant.     

Hybrid Transcatheter–Surgical Palliation

The outcome of patients with hypoplastic left heart (HLH) is determined by many factors, particularly by the first-step palliative procedure in newborns undergoing the Norwood procedure, its Sano modification, or, rarely, through challenging biventricular repairs. Duct stenting combined with bilateral pulmonary artery banding (PAB) is a new method employed as an alternative first-step approach in a number of centers worldwide. We describe this interventional–surgical “hybrid approach” as an additional strategy for the treatment of newborns with HLH syndrome and HLH complex. Between 1998 and April, 2006, 58 newborns underwent ductal stenting and bilateral PAB. These patients underwent surgical bilateral PAB initially, followed by percutaneous duct stenting; the only exception to this were patients in whom duct stenting was performed as a rescue procedure. Various balloon-expandable and self-expandable stents with different widths and lengths were used during the 8-year period of this study. Balloon dilatation of the atrial septum was performed when indicated. This included 5 patients in whom the atrial septum was stented. Aortic arch reconstruction (AAR) combined with a bidirectional cavopulmonary connection (BCPC) was performed at a median age of 4.8 months (range, 2.6–7.5), and total cavopulmonary connection (TCPC) was performed at a median age of 3.1 years (range, 2.5–4). Nine patients were listed for heart transplantation (HTX) and transplanted with AAR when a donor heart was available. Depending on growth of left ventricular structures, biventricular repair (BVR) was performed at a median age of 7.1 months (range, 3.5–10). Overall, 8 of 58 patients (13.8%) treated by the transcatheter–surgical hybrid approach died during the study period. The mortality rate for duct stenting was 1.7% (l/58), and it was 1.7% for bilateral PAB as well. Twenty-seven patients received an AAR/BCPC; 2 of them died (7.4%). Additionally, 1 of 2 patients with AAR/BCPC died while on the waiting list for HTX, resulting in a total mortality rate of 11% with an actuarial survival rate of 89%. One patient is still awaiting AAR + BCPC. Three patients died while on the waiting list for HTX despite successful bilateral PAB and duct stenting. The 30-day mortality rate for TCPC (n = 11), HTX (n = 8), and 18 patients with BVR was 0. The actuarial survival rate for patients with BVR is 93%. Postnatal transcatheter–surgical hybrid palliation expands the surgical options for newborns with HLH. Using hybrid palliation, Norwood stage I operation can be avoided in the neonatal period, the waiting period for children scheduled for cardiac transplantation can be extended, and observation for left ventricular growth suitable for biventricular repair as well.     

Safety, immunogenicity and immediate pain of intramuscular versus subcutaneous administration of a measles–mumps–rubella–varicella vaccine to children aged 11–21 months

This study compared intramuscular and subcutaneous administration of two doses of measles–mumps–rubella–varicella (MMRV) combination vaccine (Priorix-Tetra?, GlaxoSmithKline Biologicals) in children. Healthy children (N?=?328) were randomised to receive MMRV either intramuscularly or subcutaneously. Reactogenicity was similar between treatment groups for immediate vaccination pain, vaccination site pain, redness and incidence of fever and rashes. Slightly less vaccination site swelling occurred during days 0–3 of the post-vaccination period after intramuscular administration. Seroconversion rates for all components, 42–56 days post-dose 2, ranged from 99.3% to 100% in the intramuscular group and from 98.6% to 100% in the subcutaneous. Cell-mediated immunity data supported the humoral immunogenicity findings. In summary, the MMRV vaccine is well tolerated and highly immunogenic when administered either subcutaneously or intramuscularly to children in the second year of life.     

Antibody persistence for 3?years following two doses of tetravalent measles–mumps–rubella–varicella vaccine in healthy children

Two doses of a varicella-containing vaccine in healthy children <12 years are suggested to induce better protection than a single dose. Persistence of immunity against measles, mumps, rubella, and varicella as well as varicella breakthrough cases were assessed 3 years after two-dose measles, mumps, rubella, and varicella (MMRV) vaccination or concomitant MMR (Priorix™) and varicella (Varilrix™) vaccination. Four hundred ninety-four healthy children, 12–18 months old at the time of the first dose, received either two doses of MMRV vaccine (GlaxoSmithKline Biologicals) 42–56 days apart (MMRV, N = 371) or one dose of MMR and varicella vaccines administered simultaneously at separate sites, followed by another MMR vaccination 42–56 days later (MMR + V, N = 123). Three hundred-four subjects participated in 3-year follow-up for persistence of immunity and occurrence of breakthrough varicella (MMRV, N = 225; MMR + V, N = 79). Antibodies were measured by ELISA (measles, mumps, rubella) and immunofluorescence (varicella). Contacts with individuals with varicella or zoster and cases of breakthrough varicella disease were recorded. Three years post-vaccination seropositivity rates in subjects seronegative before vaccination were: MMRV-measles, 98.5% (geometric mean titer [GMT] = 3,599.6); mumps, 97.4% (GMT = 1,754.5); rubella, 100% (GMT = 51.9); varicella, 99.4% (GMT = 225.5); MMR + V-measles, 97.0% (GMT = 1,818.8); mumps, 93.8% (GMT = 1,454.6); rubella, 100% (GMT = 53.8); and varicella, 96.8% (GMT = 105.8). Of the subjects, 15–20% reported contact with individuals with varicella/zoster each year. After 3 years, the cumulative varicella breakthrough disease rate was 0.7% (two cases) in the MMRV group and 5.4% (five cases) in the MMR + V group. Conclusion: Immunogenicity of the combined MMRV vaccine was sustained 3 years post-vaccination. (208136/041/NCT00406211).     

Bubble–CPAP vs. Ventilatory–CPAP in Preterm Infants with Respiratory Distress

Objective

Application of Continuous Positive Airway Pressure (CPAP) in neonate with respiratory distress is associated with reduction of respiratory failure, reduced complications and mortality. Bubble CPAP (B-CPAP) and ventilator-derived CPAP (V-CPAP) are two most popular CPAP modes. We aimed to determine whether B-CPAP and V-CPAP would have different survival rate and possible complications.

Methods

This prospective clinical trial was performed on 50 preterm neonates weighing 1000-2000 gr who were admitted to the neonatal intensive care unit of Afzalipoor Hospital because of respiratory distress between June 2009 and May 2010. Patients were randomly allocated into treatment groups using minimization technique. Survival analysis was applied to estimate and compare survival rates. Duration of oxygen therapy, hospital stay as well as hospitalization costs were compared using independent sample t-test.

Findings

Estimated survival rates at 24 hours in B-CPAP and V-CPAP groups were 100% and 77% respectively. Corresponding figures at 48 hours were 100% and 71%. In addition the hospitalization cost in V-CPAP group was significantly higher than in B-CPAP group.

Conclusion

According to our results, B-CPAP was effective in the treatment of neonates who were suffering from respiratory distress and reduced the duration of hospital stay. In addition to mentioned benefits, its low cost may be the reason to use B-CPAP broadly compared with V-CPAP.     

de Quervain thyroiditis in a young boy following hand–foot–mouth disease

de Quervain thyroiditis is a self-limited inflammatory disorder of the thyroid gland. It is an uncommon disease in adults and very rare in children. Fritz de Quervain, a Swiss surgeon, who was an authority on thyroid disease, described the unique pathology of this disease. Granulomatous changes with giant cells in thyroid tissue are the pathological findings. Viral infection in genetically predisposed individuals has been proposed as the pathogenesis of the disease. Clinical hallmarks for the diagnosis are painful thyroid enlargement, elevated erythrocyte sedimentation rate, and C-reactive protein as well as decreased uptake of the thyroid gland on thyroid scintigraphy. In addition, thyrotoxicosis is present in about 50% of cases in early phase of the disease. Serum thyroglobulin level is usually elevated. Only symptomatic treatment with analgesics is usually required for pain relief. Glucocorticoid therapy may be used in severely ill patients. de Quervain thyroiditis is generally completely resolved without complications in 6–12 months. However, permanent hypothyroidism and recurrent disease have been reported in some patients.     

Controversies in chicken–pox immunization

Chicken–pox is one more newer vaccine in our armamentarium against infectious diseases. Due to its extremely contagious nature, varicella is experienced by almost every child or young adult in the world. Each year from 1990 to 1994, prior to availability of varicella vaccine, about 4 million cases of varicella occurred in the United States. Of these cases approximately 10,000 required hospitalization and 100 died. Although varicella is not commonly perceived as an important public health problem, the socioeconomic consequences in industrialized countries of a disease that affects practically every child and causes the carrier absence from work should not be underestimated. The varicella vaccines available in the market are safe and effective. A recent cost-benefit analysis in USA showed that routine chicken-pox vaccination is likely to save five times the investment. Even when only direct costs were considered, benefits almost balanced the costs. At present similar studies from developing countries are not available. The public health impact of varicella and zoster may be increasing in regions with high endemic rates of HIV infection. Varicella vaccine may be used either at an individual level to protect susceptible adolescents and adults, or at a population level, to cover all children as part of a national immunization programme. Vaccination of adolescents and adults will protect at-risk individuals, but will not have a significant impact on the epidemiology of the disease on a population basis. On the other hand, extensive use as a routine vaccine in children will have a significant impact on the epidemiology of the disease. If sustained high coverage can be achieved, the disease may virtually disappear. If only partial coverage can be obtained, the epidemiology may shift, leading to an increase in the number of cases in older children and adults. Hence, routine childhood varicella immunization programmes should emphasize high, sustained coverage. At present, this vaccine will have a lower priority in the National Immunization Schedule that does not have MMR and typhoid, which have a greater socioeconomic impact. Hence, at the present time WHO does not recommend the inclusion of varicella vaccination into the routine immunization programmes of developing countries.     

Ceftriaxone–Associated Nephrolithiasis in Children

Objective

Ceftriaxone is a third-generation cephalosporin which is widely used for treatment of infection in children accompanied by complications like urinary tract lithiasis and gallbladder psudolithiasis or sludge. The aim of this study was to investigate the incidence and predisposing factors that contribute to these complications in children.

Methods

This quasi-experimental and before- and after-study was conducted in 96 children who were hospitalized for treatment of different bacterial infections and received 50-100 mg/kg/day ceftriaxone divided into two equal doses intravenously under conditions of adequate hydration. Sonographic examinations of urinary tract and gallbladder were carried out before and after treatment for that purpose. Patients with positive sonographic findings after treatment were followed with serial sonographic examinations.

Findings

Post-treatment sonography demonstrated nephrolithiasis in 6 (6.3%) and gallbladder stone in one (1%), all were asymptomatic. Comparison of the groups with and without nephrolithiasis demonstrated no significant differences with respect to age, body weight, diagnosis, season of hospitalization, dosage of drug and the duration of treatment. Nephrolithiasis had a significant relation with male gender (P=0.02).

Conclusion

Our results showed that pediatric patients may develop small sized, asymptomatic renal stones during a 2-6 day course of normal or moderate dose of ceftriaxone therapy. Close monitoring of ceftriaxone treated patients especially on high dose long term therapy for nephrolithiasis and gallbladder psudolithiasis or sludge is recommended.     

The twin–twin transfusion syndrome

The aetiology of twin–twin transfusion syndrome (TTTS), which affects 10–15% of monochorionic (MC) twin pregnancies, remains poorly understood. Although all MC twins have placental vascular anastomoses, unbalanced intertwin transfusion has been shown by ex vivo injection and in vivo Doppler studies of chorionic plate vasculature to be mediated by ≥1 arterio-venous anastomoses (AVA) in association with absent bi-directional arterio-arterial anastomoses (AAA). TTTS presents in the mid trimester with the oligo-polyhydramnios sequence, the donor may have a small or non-visible bladder and abnormal umbilical artery Doppler, while the recipient has a large bladder and may develop cardiac hypertrophy, triscupid regurgitation, and eventually hydrops. Recently, discordant renal renin angiotensin expression, endothelin and atrial natriuretic peptide have been implicated in the pathogenesis. Survival has increased from <20% to <60–70% with modern treatments, although survivors remain at increased risk of antenatally acquired cerebral white matter injury, and neurodevelopmental sequelae are documented in c. 10% (range 5–23%). The recent introduction of a staging system for TTTS facilitates selection of therapy with less invasive amnioreduction and septostomy preferred for early stage disease, and more aggressive modalities such as laser ablation and cord occlusion with their attendant risk of procedure related fetal loss, reserved for advanced stage disease.     

Acquired methemoglobinemia–A sporadic Holi disaster

Objective

To study clinical profile and outcome in patients with methemoglobinemia following exposure to toxic colors during Holi festival.

Methods

This retrospective study included 112 children (5 to 12 years) admitted with methemoglobinemia after playing Holi. Clinical and treatment details were reviewed.

Results

The common symptoms were giddiness, vomiting and headache. Treatment included thorough skin wash, intravenous fluid and methylene blue in 111 children. Age 7-9 and > 11 years, vomiting, giddiness, cyanosis, PaO2 < 80 mm Hg and oxygen saturation < 95% were associated with higher need for methylene blue. All children had a good outcome.

Conclusion

Timely diagnosis and management of acquired methemoglobinemia can save lives.

     

Hemiconvulsion–Hemiplegia–Epilepsy syndrome associated with inflammatory-degenerative hystopathological findings in child with congenital adrenal hyperplasia

Hemiconvulsion–Hemiplegia (HH) syndrome represents an uncommon consequence of prolonged unilateral clonic or hemiconvulsive status epilepticus in childhood, usually occurring during a febrile illness, followed by ipsilateral hemiplegia. The subsequent appearance of focal seizures configures the so called Hemiconvulsion–Hemiplegia–Epilepsy (HHE) syndrome. The pathogenesis of HH/HHE syndrome is still unclear. We describe the case of a 4 year-old girl with congenital adrenal hyperplasia (CAH) whom developed HH/HHE syndrome with drug resistant seizures at the age of 21 months and underwent left cerebral hemispherotomy at the age of 3 years and 6 months. Histopathological findings showed the presence of an underlying inflammatory-degenerative process. Disregulation of the inflammatory cascade has been proposed as one of the possible pathogenetic mechanisms underlying HH/HHE syndrome. To our knowledge however, this is the first report of an association with a histologically documented inflammatory process. The clinical and histopathological findings of our reported case lend support to the possible role of inflammation in the pathogenesis of HH/HHE syndrome.