Aortopulmonary window: Clues to fetal diagnosis.

Being a planar structure, fetal diagnosis of aorto-pulmonary window poses great challenge. A few echocardiographic signs can help to clinch the diagnosis.

Recurrent variant c.1680C>A in FAM20C gene and genotype-phenotype correlation in a patient with Raine syndrome: a case report.

BACKGROUND: Bi-allelic mutations in FAM20C gene are known to cause a rare genetic disorder- Raine syndrome (RS). The FAM20C protein binds calcium and phosphorylates proteins involved in biomineralization of bones and teeth. RS is recognized as an osteosclerotic bone dysplasia. It is characterized by distinctive facial features, generalized osteosclerosis and respiratory insufficiency along with periosteal bone formation. RS is typically described as being an aggressive skeletal dysplasia with death in the neonatal period or early infancy. However, in the recent past an increasing number of individuals having an extended life span along with a highly heterogeneous phenotype has led to classifying RS into short and extended lifespan categories. CASE PRESENTATION: We report a case of RS with antenatal fractures, facial dysmorphism and osteosclerosis without significant respiratory manifestations. The child has a relatively extended lifespan, whereby she died at 17-months of age. Clinical exome sequencing revealed a previously known, homozygous, nonsense variant c.1680C > A (p.Cys560Ter) in exon 10 of FAM20C. Whilst the variant was initially classified as a variant of uncertain significance (VUS), through the latest release of gnomAD and GTEx data, this was subsequently re-classified as likely pathogenic. Furthermore, segregation analysis showed both parents to be carriers. In contrast, a previously reported case with the same variant had polyhydramnios, complex facial abnormalities and bright echogenic brain parenchyma with oval shaped skull and anterior flattening at 26 weeks of gestation. CONCLUSION: The variant identified has been previously reported as a VUS. The present case provides further evidence towards the pathogenicity of the variant. A plausible genotype-phenotype correlation based on the location of the variant has been verified, wherein the position of a nonsense variant in the terminal exon of FAM20C gene, could have had a partial effect on the protein function, thereby resulting in a relatively milder phenotype and extended lifespan. Furthermore, the vast phenotypic variation on clinical comparison current case and a previously reported case, despite having the same genotype, could suggest an oligogenic effect and/ or environmental influence.

Prevalence of stroke in Pakistan: Findings from Khyber Pakhtunkhwa integrated population health survey (KP-IPHS) 2016-17.

OBJECTIVE: To study the prevalence of stroke and associated risk factors in Khyber Pakhtunkhwa (KP) province of Pakistan. METHODS: This study was a part of cross-sectional KP Integrated Population Health Survey 2016-17 conducted on population aging ≥18 years at 24 districts of KP. Primary (n=1061) and secondary sampling units (n=15724) were developed, based on urban/rural and socio-economic status. Each primary-unit comprised of 250-300 households. Sample was selected through a multi-staged stratified systematic cluster sampling technique by taking every 16th household per rural and every 12th household per urban-unit. A validated "Cincinnati Stroke Scale" for identification of stroke patients in community was used along with demographics and potential risk factors. RESULTS: Among the 15724 randomly selected households, 22500 participants (51.4% females; 74.6% rural areas, mean age 42±12.6 years) were interviewed. Stroke was identified in 271 cases (137 males, 134 females; Mean age=43.39±0.85 years) and prevalence of stroke was 1.2% (1200 per 100,000 population). Obesity/overweight (38.8%), hypertension (21.8%), smoking (6.6%) and known diabetes mellitus (5.9%) were the common associated risk factors of stroke. Age groups >60 years (adjusted OR=1.68; 95% CI: 1.05-2.68); urban area (adjusted OR=1.68; 95% CI: 1.29-2.19); unemployment (adjusted OR=3.78; 95% CI: 2.49-5.73) and lower formal (primary) education (adjusted OR 2.18; 95% CI: 1.30-3.64) were significantly associated with stroke (p <0.05). CONCLUSION: Prevalence of stroke is 1.2% in the province of KP. Obesity, hypertension, smoking and Diabetes Mellitus are the common associated risk factors of stroke. Higher age, urban area, unemployment and lower formal education are significantly associated with stroke.

Isolation and molecular characterization of coxsackievirus A6 and coxsackievirus A16 from a case of recurrent Hand, Foot and Mouth Disease in Mumbai, Maharashtra, India, 2018.

Hand, Foot and Mouth Disease (HFMD) is caused by multiple Enterovirus (EV) serotypes mainly coxsackievirus A6 (CV-A6), coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71). Recurrent HFMD infections are rarely reported. An unusual rise in HFMD cases was reported in Mumbai during May-June 2018. Stool and throat swab specimens were referred from seven children from two hospitals for laboratory diagnosis. The age group of cases ranged from 9 months to 5 years with median age 13 months. Out of seven cases, three were males and four females. One 13-month-old female case was reported twice within 21 days. Stool, throat swab specimens were tested by pan enterovirus RT-PCR and also by virus isolation using human rhabdomyosarcoma cell line for detection of Enteroviruses. Out of seven HFMD cases, CV-A6 and CV-A16 viruses were isolated from five and two cases respectively. The phylogenetic analysis of CV-A6 viruses showed their similarity with CV-A6 viruses from Finland and China, whereas the two CV-A16 isolates showed similarity with those from Japan, France, China, Sarawak and Thailand. For the recurrent HFMD case, CV-A6 and CV-A16 were isolated from the stool specimens collected during the first and second episodes, respectively. There are no reports of isolation and molecular characterization of CV-A6 and CV-A16 viruses from recurrent HFMD cases. The present study reports molecular characterization of two Enterovirus serotypes CV-A6 and CV-A16 from a recurrent HFMD case, highlighting need of virological and molecular surveillance of HFMD.

Duodenal atresia with familial apple peel syndrome: case study with review of literature.

This is a case report of a neonate who was antenatally diagnosed with jejunal atresia which turned out to be duodenal atresia with apple peel syndrome. A previous sibling, who also had apple peel but with jejunal atresia, succumbed to sepsis after surgery. The first sibling had jejunal stenosis and had died of sepsis following surgery. Combination of duodenal atresia with apple peel is extremely rare. This coupled with a familial condition is rarer still. This case was challenging due to the short length of the gut and prolonged need for total parenteral nutrition and sepsis in postoperative period.

PDX1 Gene Mutation with Permanent Neonatal Diabetes Mellitus with Annular Pancreas, Duodenal Atresia, Hypoplastic Gall Bladder and Exocrine Pancreatic Insufficiency.

BACKGROUND: Neonatal diabetes mellitus is a rare condition. CASE CHARACTERISTICS: A small for gestational age male, presented with neonatal onset diabetes mellitus, duodenal atresia, annular pancreas and gall bladder hypoplasia. OBSERVATION: Observation: A novel homozygous mutation p.K163R (c.488A>G) in the PDX1 gene was found. Parents were heterozygous for the same. MESSAGE: This case highlights the importance of establishing the genetic diagnosis in all cases of neonatal diabetes mellitus.

Long-term clinical outcome of Budd-Chiari syndrome in children after radiological intervention.

OBJECTIVES: Budd-Chiari syndrome (BCS) is an uncommon cause of chronic liver disease in children. The literature on the management of pediatric BCS is scarce. Our aim was to determine the long-term outcome of patients undergoing a radiological intervention for the treatment of BCS. METHODS: Thirty-two children diagnosed with BCS between 2004 and 2014 were included. Data on the course of disease, medical management, response, and complications related to radiological interventions and outcome were collected. MAIN RESULTS: Twenty-five patients who were on regular follow-up were analyzed. The median age of the patients at presentation was 9 months (4.5-214). Sixteen patients initially received anticoagulation alone. This was associated with a high failure rate of 66%. Twenty patients underwent a radiological intervention in the form of angioplasty (n=7), hepatic vein stenting (n=3) or transjugular intrahepatic portosystemic shunt (TIPS) (n=14). Success with angioplasty was achieved in 43% of cases. Hepatic vein stenting was successful in 66%, whereas TIPS was successful in 72% of cases. TIPS was feasible in all patients. The median follow-up duration was 44 months (5-132). Four patients developed hepatopulmonary syndrome after a median period of 3 years (1.5-5.25) and one patient developed hepatocellular carcinoma. CONCLUSION: BCS commonly presents during infancy. Anticoagulation alone and angioplasty of the hepatic veins are associated with a high failure rate. Hepatic vein stenting or TIPS is feasible and efficacious in improving liver function, portal hypertension, and growth. It is associated with good long-term outcome and delays the need for liver transplantation, but may not prevent complications such as hepatopulmonary syndrome and hepatocellular carcinoma.

Seroprevalence of Toxoplasma gondii infection in yaks (Bos grunniens) on the Qinghai-Tibetan Plateau of China.

Toxoplasma gondii (T. gondii), a zoonotic parasite infects almost all warm-blooded animals and causes significant economic losses. To date, however, it is still unclear whether yaks from the Qinghai-Tibetan plateau of China are exposed to T. gondii. On the present study, a survey was conducted for the first time, to investigate the seroprevalence of T. gondii infection in yaks (Bos grunniens) on the Qinghai-Tibetan Plateau (Qinghai, Tibet, Hongyuan area of Sichuan province). A total of 905 and 736 serum samples were collected from yaks in these areas in 2012 and 2013, respectively and assayed for T. gondii antibodies by an indirect hemagglutination test (IHA). The results showed that seroprevalence on plateau was 21.7% and 29.1% in 2012 and 2013, respectively with the prevalence of 22.4%, 19.4% and 25.5% in 2012 for Qinghai, Tibet and Hongyuan of Sichuan, respectively and of 26.4%, 27.0% and 33.7% for these three regions in 2013, respectively. The present survey indicated that the infection with T. gondii in yaks was widely spread in recent years on the plateau causing a high risk factor for animals and humans.

Feasibility of exclusive enteral feeds from birth in VLBW infants >1200 g--an RCT.

AIM: To evaluate the feasibility of initiation of exclusive enteral feeds on first day of life in very low birthweight infants >1200 g. METHODS: Haemodynamically stable infants with birthweights 1200-1500 g irrespective of gestational age were randomized into two groups. STUDY GROUP: Enteral feeds 80 mL/kg/day started within 1 h of birth and increased by 20 mL/kg/day to 180 mL/kg/day. No intravenous fluids given. CONTROL GROUP: Intravenous fluids 50 mL/kg/day started along with enteral feeds 30 mL/kg/day within 1 h of birth and increased by 20 mL/kg/day to 180 mL/kg/day. The outcome measures were - primary: time to regain birthweight and secondary: duration of hospital stay, incidence of necrotizing enterocolitis and sepsis. RESULTS: Twenty three babies randomized in each group. Infants in study group regained birthweight earlier [mean 5.52 days, SD ± 2.94] compared to those in control group [mean 12.7 days, SD ± 2.25] (p < 0.0001). Duration of hospital stay was lower in study group [mean 15.04 days, SD ± 5.26] compared to those in control group [mean 28.04 days, SD ± 6.76] (p < 0.0001). No necrotizing enterocolitis detected. CONCLUSION: It is feasible to initiate exclusive enteral feeds from first day of life in stable infants with birthweight between 1200 and 1500 g without any parenteral fluid support. It leads to twice as faster regaining of birthweight and halves duration of hospital stay.

Budd-Chiari syndrome in children: experience with therapeutic radiological intervention.

OBJECTIVES: Budd-Chiari syndrome (BCS) in children is not uncommon. Published literature on therapy for this condition is scarce. We therefore attempted radiological interventions in these patients to determine their efficacy and safety. PATIENTS AND METHODS: Fourteen of 16 children with a median age of 22 months diagnosed as having BCS were subjected to an inferior vena cava/hepatic venogram with the aim to establish a normal antegrade flow in at least 1 hepatic vein (HV). RESULTS: A normal antegrade flow in at least 1 of the HVs could be established in 11 children. Three patients had angioplasty of the HV (vein size or=5 mm), and 6 had transjugular intrahepatic porta systemic shunt ([TIPSS] total occlusion of all 3 HVs or veno-occlusive disease). The youngest child undergoing a successful stenting was 7 months of age and the child undergoing TIPSS was 3 years of age. One patient had reversal of fulminant liver failure following a successful TIPSS. Postprocedure, 2 patients developed reversible encephalopathy and 1 had a neck hematoma. There was no procedure-related mortality. The procedure was successful in both patients with stenting (100%), 5 of the 6 patients with TIPSS (80%), and only 1 of the 4 patients (25%) with angioplasty. The median follow-up was 31 months. CONCLUSIONS: Radiological therapeutic intervention is feasible and safe in children with BCS. The overall results of stenting/TIPSS are better than with angioplasty; however, long-term results of these interventions need to be evaluated.

Capillaria hepatica infestation.

Capillaria hepatica is a very rare zoonotic infestation which primarily infests rodents and is rarely found in humans. The presenting features are fever of unknown origin, hepatomegaly and peripheral eosinophilia. Liver biopsy remains the cornerstone of diagnosis. Treatment of choice is Albendazole and outcome is generally good.

Reversal of severe hepato-pulmonary syndrome in congenital hepatic fibrosis after living-related liver transplantation.

We report a 5-year-old girl with congenital hepatic fibrosis who presented with clubbing and cyanosis. Partial pressure of oxygen was 40 mmHg with oxy-gen saturation of 70% on room air, which improved to 128 mmHg and 92% on inhalation of 100% oxygen. Macroaggregated albumin scan showed 58% shunting to the brain, suggestive of severe hepatopulmonary syndrome. Echocardiogram and pulmonary angiogram ruled out pulmonary hypertension. Four weeks after living-related liver transplantation, she had normal blood gases and reduction in shunting to 7% on macroaggregated albumin scan.

Population pharmacokinetics of theophylline during paediatric extracorporeal membrane oxygenation.

AIMS: To determine the population pharmacokinetics of theophylline during extracorporeal membrane oxygenation (ECMO) from routine monitoring data. METHODS: Retrospective data were collected from 75 term neonates and children (age range 2 days to 17 years) receiving continuous infusions of aminophylline (mean rate 9.2 +/- 2.6 micro g kg-1 min-1) during ECMO. A total of 160 plasma concentrations (range 1-8 per patient), sampled at time intervals ranging from 10 h to 432 h, were included. Population PK analysis and model building were carried out using WinNonMix Professional (Version 2.0.1). Cross-validation was used to evaluate the validity and predictive accuracy of the model. RESULTS: A one-compartment model with first order elimination combined with an additive error model was found to best describe the data. Of the covariables tested, bodyweight significantly influenced clearance and volume of distribution, whereas age was an important determinant of clearance, as adjudged by the differences in the -2 x log likelihood (P < 0.005) and the residual error value. The final model parameters were estimated as: clearance (l h-1) = 0.023 x bodyweight (kg) + 0.000057 x age (days) and volume of distribution (l) = 0.57 x bodyweight (kg). The interindividual variability in clearance and volume of distribution was 38% and 40%, respectively. The residual error corresponded to a standard deviation of 3.6 mg l-1. Cross-validation revealed a median (95% confidence interval) model bias of 9.4% (2.9, 16.5%) and precision of 29.5% (24.8, 36.0%). CONCLUSIONS: The estimated clearance is significantly lower, and volume of distribution higher, than previously reported in non-ECMO patients of similar age. These differences are probably a result of the expanded circulating volume during ECMO and altered renal and hepatic physiology in this critically ill group. Large interindividual variability reflects the heterogeneous nature of patients treated on ECMO.

Bilateral neuroretinitis associated with mumps.

BACKGROUND: Involvement of the optic nerve is a rare complication of mumps infection. OBJECTIVES: To report a case of bilateral neuroretinitis complicating a mumps infection and to review 5 previously reported cases. DESIGN: Case report and literature review. SETTING: Tertiary hospital. PATIENT: A 7-year-old girl had sudden-onset blindness due to bilateral neuroretinitis. Approximately 3 weeks prior to the initial examination, she developed a self-limited febrile illness with parotid swelling and subsequent meningoencephalitis. RESULTS: Mumps was determined to be the underlying cause of the meningoencephalitis and bilateral optic neuritis because of the exposure history in this nonvaccinated child, the typical clinical signs and symptoms, and the positive serologic test results. Recovery of visual function was gradual but nearly complete. CONCLUSIONS: Physicians should be aware that optic nerve involvement may be a manifestation of mumps infection. The delayed onset of optic neuritis, the bilateral involvement, and the near complete recovery suggest an immune-mediated pathogenesis.