Metabolic parameters and fetal development in offspring of mothers with gestational diabetes

Introduction: Increasing incidence of GDM and LGA births predispose children for obesity related diseases, metabolic syndrome and type 2 Diabetes. Aims: The aim of the study was to investigate the cause of enhanced fetal growth (>90 centiles)in well controlled gestational diabetic pregnancies. Subjects and methods: 37 GDM mothers and 46 healthy control subjects and their newborns participated in the cross sectional study. Blood samples were taken from mother before delivery and from neonates at the time of delivery and tested for concentration of adiponectin, leptin, insulin, c peptide, cholesterol, triglycerides, HDL and LDL cholesterol. Results: Gestational diabetic mothers had significantly higher BMI (first trimester) than a control group (29.6 ±6.0 vs. 23.3 ± 4.3, P<0.0001) and adiponectin concentration were significantly lower in gestational diabetic mothers compared with healthy control subjects (10871.3 ± 5184.2 vs. 13418.9 ± 5148.6, P=0.021). In offspring of GDM concentration of adiponectin (24469.0 ± 10478.8 vs. 45359.6 ± 7592, P=0.0017) is significantly lower in LGA newborns of GDM mothers compared with LGA newborns of healthy control; and concentration of Insulin is significantly higher in AGA (11.3 ±14.1 vs.4.3 ±3.2, P<0.0001) and LGA (12.9 ±6.4 vs. 5.8 ±2.9, P=0.035) newborn of GDM mothers compared with AGA and LGA newborns of healthy control. Conclusions: The findings of this study describe an altered metabolic environment for the fetus even in well controlled GDM mothers. Hyperinsulinemia and hypoadiponectinemia in macrosomic infants are predisposing factors that can contribute in development of obesity related disorder later in their life

Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome

Abstract Wolcott-Rallison syndrome (WRS), caused by mutation in the EIF2AK3 gene encoding the PERK enzyme, is the most common cause of permanent neonatal diabetes mellitus (PNDM) in consanguineous families and isolated populations. Besides PNDM, it also includes skeletal abnormalities, liver and renal dysfunction, and other inconsistently present features. We present two siblings, who are WRS patients, and are Albanians from Kosovo born to unrelated parents. The older sister presented with PNDM, exocrine pancreatic insufficiency, short stature, microcephaly, normocytic anemia, delay in speech development, skeletal abnormalities, primary hypothyroidism, and hypoplastic nipples. Sequencing of the EIF2AK3 gene identified a homozygous mutation R902X in exon 13. The younger brother was diagnosed with PNDM and died from hepatic failure suggesting that he has been suffering from WRS as well. Including one previously reported patient from Kosovo carrying the same homozygous mutation, there are three WRS patients from this very small, ethnically homogenous region suggesting founder effect in this population. Conclusion: We postulate that thyroid hypoplasia with primary subclinical hypothyroidism already reported in two WRS patients and nipple hypoplasia could also be the phenotypic reflection of the mutation of pleiotropic EIF2AK3 gene in secretory cells

Phenylketonuria screening and management in southeastern Europe - survey results from 11 countries

Background: We aimed to assess the current state of PKU screening and management in the region of southeastern Europe. Methods: A survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014. Results: Responses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient's PKU society existed in 7 of 11 countries. Conclusions: The region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects

Phenylketonuria screening and management in southeastern Europe - survey results from 11 countries

Background: We aimed to assess the current state of PKU screening and management in the region of southeastern Europe. Methods: A survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014. Results: Responses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient's PKU society existed in 7 of 11 countries. Conclusions: The region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects

Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders (“conditions”) then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40–50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together

Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together

Clinical presentation of new onset of Diabetes Mellitus in children and adolescents during the period of Covid-19 pandemic

Diabetes Mellitus type 1 is one of the most common endocrinological disease in children. As in many countries of the world, also in Kosovo, the number of children and teenagers affected by diabetes is increasing. The aim of the presentation was to evaluate the number of new cases of diabetes in children and adolescents and the rate of Diabetic Ketoacidosis at the time of diagnosis at the Referral Center for Diabetes, Pediatric Clinic in Prishtina during the period of Covid 19 pandemic compared to previous years. Methodology: The research was retrospective in nature, the data from the hospital records of 220 patients were evaluated. The data of the first group of patients were collected from the period before Covid pandemic (from January 2015 to February 2020) and the second group were the patients presented during the period of Covid pandemic ( from March 2020 until April 2021). Results: The frequency of new cases of diabetes during the period of Covid 19 has not shown a significant increase, but their clinical presentation in a state of severe diabetic ketoacidosis has been 30% higher compared with the period before Covid pandemic and with a fatal outcome in two teenage children. Conclusions: The risk of severe diabetic ketoacidosis in new cases of diabetes has been more pronounced during the period of Covid 19 pandemic. It must be necessary to reorganize the health system in particular during such situations to prevent the deterioration of the condition of children and adolescents with diabetes

The Influence of Type 1 Diabetes Mellitus on Dental Caries and Salivary Composition

Diabetes mellitus is the most common chronic disease that affects the oral health. The aim of the study is to evaluate the dental caries, salivary flow rate, buffer capacity, and Lactobacilli in saliva in children with type 1 diabetes mellitus compared to the control group. Methods. The sample consisted of 160 children of 10 to 15 years divided into two groups: 80 children with type 1 diabetes mellitus and 80 children as a control group. Dental caries was assessed using the DMFT index for permanent dentition. Stimulated saliva was collected among all children. Salivary flow rate and buffer capacity were measured, and the colonies of Lactobacillus in saliva were determined. The observed children have answered a number of questions related to their dental visits and parents’ education. The data obtained from each group were compared statistically using the chi-square test and Mann–Whitney U-test. The significant level was set at p<0.05. Results. DMFT in children with type 1 diabetes was significantly higher than that in the control group (p<0.001). Diabetic children have a low level of stimulated salivary flow rate compared to control children (0.86 ± 0.16 and 1.10 ± 0.14). The buffer capacity showed statistically significant differences between children with type 1 diabetes and control group (p<0.001). Also, children with type 1 diabetes had a higher count and a higher risk of Lactobacillus compared to the control group (p<0.05 and p<0.001). Conclusion. The findings we obtained showed that type 1 diabetes mellitus has an important part in children’s oral health. It appears that children with type 1 diabetes are exposed to a higher risk for caries and oral health than nondiabetic children

Hashimoto thyroiditis and nephrocalcinosis in a child with down syndrome

Introduction: Hypothyroidism has been reported to affect renal function and structure. However, the association of hypothyroidism with distal renal tubular acidosis (dRTA) is rarely reported in children. Case Presentation: We present a 6-year-boy with Down syndrome admitted in our department due to vomiting, weakness, polyuria, polydipsia, irritability and weight loss in the last few weeks. Investigations revealed features of hypokalemia, metabolic acidosis and alkaline urine consistent with dTRA. Abdominal ultrasound found nephrocalcinosis. In addition, Antithyroid peroxidase antibodies were positive, suggesting an autoimmune background for the pathogenesis of the tubular dysfunction. Treatment for dRTA and hypothyroidism was started and symptomatic improve was noticed. Conclusion: DRTA should be excluded in children with autoimmune disorders who develop weakness, polyuria, polydipsia or growth failure. Early diagnosis would reduce long-term complications