Post-synaptic scaffold protein TANC2 in psychiatric and somatic disease risk

Understanding the shared genetic aetiology of psychiatric and medical comorbidity in neurodevelopmental disorders (NDDs) could improve patient diagnosis, stratification and treatment options. Rare TANC2 (Tetratricopeptide Repeat, Ankyrin Repeat and Coiled-Coil Containing 2) disrupting variants were disease-causing in NDD patients. This post-synaptic scaffold protein, essential for dendrite formation in synaptic plasticity, plays an unclarified but critical role in development. We here report a novel homozygous-viable Tanc2 disrupted function model where mutant mice were hyperactive and had impaired sensorimotor gating consistent with NDD patient psychiatric endophenotypes. Yet, a multi-systemic analysis revealed the pleiotropic effects of Tanc2 outside the brain such as growth failure and hepatocellular damage. This was associated with aberrant liver function including altered hepatocellular metabolism. Integrative analysis indicates that these disrupted Tanc2 systemic effects relate to interaction with Hippo developmental signalling pathway proteins and will increase the risk for comorbid somatic disease. This highlights how NDD gene pleiotropy can augment medical comorbidity susceptibility underscoring the benefit of holistic NDD patient diagnosis and treatment for which large-scale preclinical functional genomics can provide complementary pleiotropic gene function information.

Late Endocrine Effects after Stem Cell Transplant in a Young Girl with Griscelli Syndrome

Background. Griscelli syndrome (GS) is a rare disorder characterized by partial albinism and silver hair with alteration in genes necessary for melanin transport. Type 2 GS is fatal due to severe immunodeficiency without curative stem cell transplant (SCT). Late endocrinopathies are quite common in other disorders after SCT. These complications have not been reported in GS. Case Presentation. A 7-year-old female presented for growth failure with a history of GS status post curative SCT and consequently developed graft-versus-host disease (GvHD). She also had a history of eosinophilic enterocolitis, for which she was taking supraphysiologic glucocorticoids for the past year. She presented with severe short stature along with mild hyperthyroxinemia with subsequent diagnosis of Graves’ disease, which was treated with methimazole. GH therapy was commenced due to persistent growth failure, with a robust increase in growth parameters. She started spontaneous puberty; however, initial biochemical evaluation revealed hypergonadotropic hypogonadism with undetectable anti-Mullerian hormone (AMH) consistent with low ovarian reserve and premature ovarian failure. Discussion. Growth failure was multifactorial due to her inflammatory condition and poor weight gain from multiple underlying illnesses, including hyperthyroidism, as well as chronic supraphysiologic glucocorticoid use. Although hypothyroidism is more commonly seen after SCT, rare cases of hyperthyroidism have been reported. In addition to SCTs, GvHD and GS have been associated with autoimmune conditions. It is important to monitor pubertal progression as the majority of those treated with alkylating agents prior to SCT have pubertal and ovarian failure and remain at risk for premature menopause.

Mauriac Syndrome in a Nigerian child with Type 1 Diabetes Mellitus: A Case Report

A 14-year-old boy with Type 1 Diabetes mellitus (diagnosed at eight years of age) presented with complaints of fever, weight loss, growth failure, pubertal delay, abdominal swelling and discomfort. He was on Premixed insulin (70/30) with inadequate follow-up and poor diabetic control. Examination revealed cachexia, generalised lymphadenopathy, a protuberant abdomen and hepatosplenomegaly. Anthropometry showed a bodyweight of 19.6kg, a height of 116cm and a BMI of 14.1kg/m2, all markedly below the 3rd centile. He had no secondary sexual characteristics: axillary hair stage 1, pubic hair stage 1, penile length of 4.9cm and prepubertal testicular volumes of 3mls bilaterally. At presentation, his random blood glucose was 400mg/dl, and glycosylated haemoglobin was 11.6%. Screening for tuberculosis, human immunodeficiency virus, hepatitis and lymphoproliferative disorders were negative. Other blood investigation findings included leucocytosis, erythrocyte sedimentation rate of 30mm/hr, normal liver function tests, normal serum electrolytes, urea and creatinine. His haemoglobin genotype was AS. Chest radiograph showed features of bronchopneumonia. A presumptive diagnosis of Mauriac Syndrome was made. With the optimisation of glycaemic control, he improved clinically with a weight gain of 5.7kg over four months and resolution of hepatosplenomegaly.

Postnatal Growth Restriction in Preterm Infants: A Major Impact of Nutritional Practices and Methods of Assessment

Background: Nutritional management of preterm infants represents a significant challenge for most practitioners caring for sick and/or premature babies. Despite aggressive parenteral and enteral alimentation, a considerable number of preterm infants continue to fall far short of expected growth trajectories that match infants of similar gestation in-utero. Postnatal growth failure may be associated with future neurodevelopmental and cognitive impairments. Objective: The aim of the research is to investigate the incidence of postnatal growth restriction (PNGR) and characteristics of nutritional practices and growth parameters in a cohort of preterm infants born <32 weeks’ gestational age (GA) in a single neonatal intensive care unit (NICU). Methodology: This prospective study included 130 preterm infants born <32 weeks’ GA and admitted to the NICU between February 2018 and January 2020. The infants were divided into two groups: A (GA 23–26+6 weeks [n=50]) and B (27–31+6 weeks [n=80]). The association between PNGR and predicting risk factors was evaluated using logistic regression models. Results: PNGR was found in 62 (47%) infants at 28 days of life and increased to 73% of infants at 36 weeks’ postmenstrual age. Low birth weight and GA were independent factors predicting growth failure. PNGR was significantly correlated with birth weight (p < 0.01), length (p < 0.002), and GA (p < 0.03) at birth; however, HC was not a predictor of PNGR at 28 days. At 36 weeks’ PMA or discharge, PNGR was more pronounced in length, with a mean Z-score of -3.0, followed by weight, with a mean Z-score of -2.1, and an HC Z-score of -1.4. Conclusion : PNGR was significantly high in preterm infants <32 weeks’ gestation. A significant nutritional gap still exists between the recommended and actual caloric and protein supplementation, especially in the first few days after birth. Delayed optimization of caloric intake may be insufficient to promote growth trajectories, especially in preterm infants with significant morbidities.

Rickets guidance: part I—diagnostic workup

Rickets is a disease of the growing child arising from alterations in calcium and phosphate homeostasis resulting in impaired apoptosis of hypertrophic chondrocytes in the growth plate. Its symptoms depend on the patients’ age, duration of disease, and underlying disorder. Common features include thickened wrists and ankles due to widened metaphyses, growth failure, bone pain, muscle weakness, waddling gait, and leg bowing. Affected infants often show delayed closure of the fontanelles, frontal bossing, and craniotabes. The diagnosis of rickets is based on the presence of these typical clinical symptoms and radiological findings on X-rays of the wrist or knee, showing metaphyseal fraying and widening of growth plates, in conjunction with elevated serum levels of alkaline phosphatase. Nutritional rickets due to vitamin D deficiency and/or dietary calcium deficiency is the most common cause of rickets. Currently, more than 20 acquired or hereditary causes of rickets are known. The latter are due to mutations in genes involved in vitamin D metabolism or action, renal phosphate reabsorption, or synthesis, or degradation of the phosphaturic hormone fibroblast growth factor 23 (FGF23). There is a substantial overlap in the clinical features between the various entities, requiring a thorough workup using biochemical analyses and, if necessary, genetic tests. Part I of this review focuses on the etiology, pathophysiology and clinical findings of rickets followed by the presentation of a diagnostic approach for correct diagnosis. Part II focuses on the management of rickets, including new therapeutic approaches based on recent clinical practice guidelines.

Most Short Children with Cystic Fibrosis Do Not Catch Up by Adulthood

Poor linear growth is common in children with cystic fibrosis (CF) and predicts pulmonary status and mortality. Growth impairment develops in infancy, prior to pulmonary decline and despite aggressive nutritional measures. We hypothesized that growth restriction during early childhood in CF is associated with reduced adult height. We used the Cystic Fibrosis Foundation (CFF) patient registry to identify CF adults between 2011 and 2015 (ages 18–19 y, n = 3655) and had height for age (HFA) records between ages 2 and 4 y. We found that only 26% CF adults were ≥median HFA and 25% were <10th percentile. Between 2 and 4 years, those with height < 10th percentile had increased odds of being <10th percentile in adulthood compared to children ≥ 10th percentile (OR = 7.7). Of HFA measured between the 10th and 25th percentiles at ages 2–4, 58% were <25th percentile as adults. Only 13% between the 10th and 25th percentile HFA at age 2–4 years were >50th percentile as adults. Maximum height between ages 2 and 4 highly correlated with adult height. These results demonstrate that low early childhood CF height correlates with height in adulthood. Since linear growth correlates with lung growth, identifying both risk factors and interventions for growth failure (nutritional support, confounders of clinical care, and potential endocrine involvement) could lead to improved overall health.

Socioeconomic inequalities in child growth failure in Ethiopia: findings from the 2000 and 2016 Demographic and Health Surveys

ObjectiveSocioeconomic inequalities in child growth failure (CGF) remain one of the main challenges in Ethiopia. This study examined socioeconomic inequalities in CGF and determinants that contributed to these inequalities in Ethiopia.MethodsThe Ethiopia Demographic and Health Surveys 2000 and 2016 data were used in this study. A pooled unweighted sample of the two surveys yielded 21514 mother–child pairs (10873 in 2000 and 10641 in 2016). We assessed socioeconomic inequalities in CGF indicators using the concentration curve and concentration index (CI). We then decomposed the CI to identify percentage contribution of each determinant to inequalities.ResultsSocioeconomic inequalities in CGF have increased in Ethiopia between 2000 and 2016. The CI increased from −0.072 and −0.139 for stunting, −0.088 and −0.131 for underweight and −0.015 and −0.050 for wasting between 2000 and 2016, respectively. Factors that mainly contributed to inequalities in stunting included geographical region (49.43%), number of antenatal care visits (31.40%) and child age in months (22.20%) in 2000. While in 2016, inequality in stunting was contributed mainly by wealth quintile (46.16%) and geographical region (−13.70%). The main contributors to inequality in underweight were geographical regions (82.21%) and wealth quintile (27.21%) in 2000, while in 2016, wealth quintile (29.18%), handwashing (18.59%) and access to improved water facilities (−17.55%) were the main contributors. Inequality in wasting was mainly contributed to by maternal body mass index (−66.07%), wealth quintile (−45.68%), geographical region (36.88%) and paternal education (33.55%) in 2000, while in 2016, wealth quintile (52.87%) and urban areas of residence (-17.81%) were the main driving factors.ConclusionsThis study identified substantial socioeconomic inequalities in CGF, and factors that relatively contributed to the disparities. A plausible approach to tackling rising disparities may involve developing interventions on the identified predictors and prioritising actions for the most socioeconomically disadvantaged groups.

Analisis Ketahanan Pangan dan Karakteristik Rumah Tangga dengan Kejadian Stunting

Stunting is a condition of chronic growth failure experienced by toddlers that can cause children to experience difficulties in achieving optimal growth and development according to their age. Stunting can be minimized if the factors that affect stunting in the region can be controlled properly. Many factors are thought to influence the incidence of stunting, one of which is food security. If food insecurity occurs in a household, this can increase the proportion of stunting events that are increasing which can directly increase the national stunting incidence rate and will continue to be a major health problem in Indonesia. Indonesia. The purpose of this study was to analyze the relationship between household food security and household social factors with the incidence of stunting. The research was conducted in Palembang City, precisely at the 11 Ilir Health Center in Palembang. The research method used is a cross-sectional design. The determination of the research sample was carried out by purposive sampling based on the inclusion and exclusion criteria of the sample that had been determined in this study. The research sample was toddlers aged 0 – 59 months totaling 40 people. Analysis of the data used is chi-square with = 0.05. In this study, it was found that there was a significant relationship between household food security (p = 0.031), and household size (p = 0.000) with the incidence of stunting, while for the variable mother's age (p = 0.393) and mother's education level (p = 0.283) is known to have no significant relationship with the incidence of stunting. Household food security is directly related to the incidence of stunting, families in households who are not food insecure tend to have children under five who are classified as stunting, this is due to the lack of nutritional intake received both in terms of quantity and quality and does not meet the nutritional adequacy standard for stunting toddlers. It is hoped that to reduce the incidence of stunting, the government needs to add a local food-based work program in reducing the incidence of stunting.

Using Nature to Nurture: Breast Milk Analysis and Fortification to Improve Growth and Neurodevelopmental Outcomes in Preterm Infants

Premature infants are born prior to a critical window of rapid placental nutrient transfer and fetal growth—particularly brain development—that occurs during the third trimester of pregnancy. Subsequently, a large proportion of preterm neonates experience extrauterine growth failure and associated neurodevelopmental impairments. Human milk (maternal or donor breast milk) is the recommended source of enteral nutrition for preterm infants, but requires additional fortification of macronutrient, micronutrient, and energy content to meet the nutritional demands of the preterm infant in attempts at replicating in utero nutrient accretion and growth rates. Traditional standardized fortification practices that add a fixed amount of multicomponent fortifier based on assumed breast milk composition do not take into account the considerable variations in breast milk content or individual neonatal metabolism. Emerging methods of individualized fortification—including targeted and adjusted fortification—show promise in improving postnatal growth and neurodevelopmental outcomes in preterm infants.