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

UNLABELLED: 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.

Current Status of Newborn Screening in Southeastern Europe.

Significant part of Southeastern Europe (with a population of 76 million) has newborn screening (NBS) programs non-harmonized with developed European countries. Initial survey was conducted in 2013/2014 among 11 countries from the region (Albania, Bulgaria, Bosnia and Herzegovina (BIH), Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, and Slovenia) to assess the main characteristics of their NBS programs and their future plans. Their cumulative population at that time was ~52,5 million. At that time, none of the countries had an expanded NBS program, while phenylketonuria screening was not introduced in four and congenital hypothyroidism in three of 11 countries. We repeated the survey in 2020 inviting the same 11 countries, adding Cyprus, Greece, Hungary, and Malta (due to their geographical position in the wider region). The aims were to assess the current state, to evaluate the change in the period, and to identify the main obstacles impacting the implementation of expanded NBS and/or reaching a wider population. Responses were collected from 12 countries (BIH-Federation of BIH, BIH-Republic of Srpska, Bulgaria, Croatia, Greece, Hungary, Kosovo, North Macedonia, Malta, Montenegro, Romania, Serbia, Slovenia) with a population of 68.5 million. The results of the survey showed that the regional situation regarding NBS only modestly improved in this period. All of the surveyed countries except Kosovo screened for at least congenital hypothyroidism, while phenylketonuria was not screened in four of 12 countries. Croatia and Slovenia implemented an expanded NBS program using tandem mass spectrometry from the time of last survey. In conclusion, the current status of NBS programs in Southeastern Europe is very variable and is still underdeveloped (or even non-existent) in some of the countries. We suggest establishing an international task-force to assist with implementation and harmonization of basic NBS services where needed.

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.

Prevalence of gestational diabetes mellitus according to IADPSG and NICE criteria.

OBJECTIVE: To investigate the impact of the International Association of Diabetic Pregnancy Study Group (IADPSG) diagnostic criteria on the prevalence of gestational diabetes mellitus (GDM) and overt diabetes as compared with the UK National Institute for Health and Care Excellence (NICE) criteria, and to evaluate the prevalence of maternal and perinatal outcomes among pregnant women with fasting plasma glucose (FPG) levels of 5.1-5.5 mmol/L. METHODS: A retrospective study was undertaken of data for women who underwent a 2-hour 75-g oral glucose tolerance test at 24-32 weeks of a singleton pregnancy at a center in Croatia between January 2012 and December 2014. RESULTS: Among 4646 included women, 1074 (23.1%) had GDM according to IADPSG criteria, 826 (17.8%) would be diagnosed according to NICE criteria, and 50 (1.1%) had overt diabetes. FPG levels were 5.1-5.5 mmol/L for 409 (8.8%) women. Compared with a control group (n=3391), these women had higher odds of large-for-gestational-age newborns (odds ratio 3.7, 95% CI 2.0-4.6) and cesarean delivery (odds ratio 1.8, 95% CI 1.3-2.3). CONCLUSION: Women with FPG levels of 5.1-5.5 mmol/L have an increased risk of adverse maternal and perinatal outcome, although they would not be diagnosed with GDM according to NICE criteria.