Extrathyroidal congenital defects in children with congenital hypothyroidism - observations from a single paediatric centre in Central Europe with a review of literature.

INTRODUCTION: Patients with congenital hypothyroidism (CH) can have an increased risk of occurrence of extrathyroidal defects compared to the general population, which could influence their development. The abnormalities occur mainly in organ systems whose development and function is dependent on genes that are also responsible for proper organogenesis of the thyroid gland and thyroid hormone synthesis. AIM OF THE STUDY: The aim of the study was to evaluate the frequency of extrathyroidal defects in CH patients, taking into consideration the cause of this co-occurrence and the role of genetic tests. MATERIAL AND METHODS: The study included 54 newborns with positive screening test for CH based on elevated TSH level, in the years 2010-2017, from South-Eastern Poland. The data was retrieved retrospectively from patients' medical records. RESULTS: Twenty of 54 newborns with CH (37%) had congenital defects of other organs. In 10 (18.5%) cardiac defects were found, in 5 (9.25%) abnormal symptoms of the respiratory system, 7 (12.96%) had abnormalities of the gastrointestinal system, five (9.25%) had genitouri-nary abnormalities, 3 (5.55%) had abnormalities of the nervous system, and 6 (11.1%) had musculoskeletal abnormalities. CONCLUSIONS: The analysis of our data and current literature suggests that genetic factors play the most important role in the development of extrathy-roidal abnormalities in newborns with CH. Identifying the mutation causing CH, the potential defects that can accompany newborns with CH, screening could be offered for these patients in order to obtain an earlier diagnosis and implement early and appropriate treat-ment.

[Neonatal mass screening for cystic fibrosis in south-east Poland]. / Badania przesiewowe noworodków w kierunku mukowiscydozy w Polsce poludniowo-wschodniej.

UNLABELLED: The objective of neonatal mass screening programs that are obligatory in Poland is an early detection of congenital diseases: hypothyreosis, phenylketonuria and cystic fibrosis. Cystic fibrosis is the most common genetic monogenic disease affecting Caucasian individuals and having an autosomal recessive inheritance pattern. Neonatal screening for cystic fibrosis allows for diagnosing the disease in the first month of life and early introduction of preventive-therapeutic management. In the period between June 1, 2009 and July 31, 2010, a total of 82,250 newborns were screened in the Krakow mass screening lab. METHODS: Determinations of immunoreactive tripsin (IRT) by ELISA, and DNA analysis (searching for mutations in the CFTR gene by sequencing) if IRT was above 99.4 centile in blood on filter paper. The incidence of cystic fibrosis in south-east Poland was determined as 1:7,477, and carriership as 1:2,006. Of newborns with confirmed cystic fibrosis, five presented with signs of malnutrition, edemas, intrahepatic cholestasis and anemia. Almost all of these children passed fatty stools. Two were diagnosed with active CMV infections. CONCLUSIONS: 1) Neonatal mass screening allows for early detection of cystic fibrosis and introduction of appropriate therapeutic management (prevention of malnutrition through supplying appropriate amount of protein, essential fatty acids, pancreatic enzymes and vitamin A and E supplementation). 2) Children are recalled for diagnosis verification immediately after genetic test results are available, what maximally shortens the time needed for confirming the disease.

[Did the change of technique of screening investigations influence on improvement of test credibility in recognizing and differentiating diagnostics of hiperphenylalaninemias?]. / Czy zmiana techniki badan przesiewowych wplynela na poprawe wiarygodnosci testu w rozpoznawaniu i diagnostyce róznicowej hiperfenyloalaninemii?

UNLABELLED: The phenylketonuria (PKU)/hyperphenylalaninemia (HPA) it is the most frequent inborn genetically conditioned error of metabolism of amino acids. It's occurrence in Polish population was estimated on the level 1:7.000 - 8.500. A. Folling was the first who described the phenylketonuria in 1934. It's diagnosed by neonatal screening, which was initiated in 1963 by prof. R. Guthrie. MATERIAL: since 1985 till 2007 1,172,310 newborns investigated by the neonatal screening proceeding by the Laboratory of Screening and Inborn Errors of Metabolism in Cracow. METHOD: in the years 1985-1998 the phenylalanine concentration in drop of blood on the blotting-paper was measured with half-quantitative Guthrie method. However after 1999 the colorimetric quantitative method measurement of phenylalanine concentration in capilar blood was introduced. It 2004 the cut-off value of phenylalanine in drop of blood on filter paper in neonatal screening investigation has was established below 3 mg/dl (till 2003 it was below 4mg/ dl). The blood had been taken from every newborn on filter paper Standard 903 between third and seventh day of the child's life. The verification of recognition in 1985-1988 was applied by Guthrie test, in 1989-2006 by the fluorymetric McCaman and Robins method, and since 2007 by colorimetric method. RESULTS: in 1985-1998 the group of 137 newborns was distinguished due to the newborn screening (1:4.204), the classic PKU was recognized at 96 (1:5.999), however in next years (after change of method) due to screening 186 (1:4.788) newborns were distinguished, the classic PKU was recognized at 94 (1:5.236) newborn children. The lowering the point of cut-off influenced on frequency recognizing mild HPA, which grew up from 1:25.909 to 1:12.720. In 2001 we verified the recognition at 51 of 93 women (data were have gained over from archive of Outpatient Department), who where identified by the neonatal screening in 1985-1998, and in the face of observed phenylalanine values (<10 mg/dl - mild HPA) did not require dietetic treatment, and they gave up with medical care gradually. With regard on possibility pronouncement the signs of maternal PKU at their offspring, we ask 45 of them to contact with our Outpatient Clinic again, but only 36 with different reasons answered, at 28 of them the phenylalanine concentration was raised: 2-4 mg/dl - in 1 patient; 4-6 mg/ dl - in 6 patients; 6-10 mg/dl - in 11 patients; 10-20 mg/dl - in 12 patients. With this reason at 19 women the low-phenylalanine diet had to be introduce. CONCLUSIONS: 1. Applied Guthrie test limited the individual differentiating diagnostics of HPA, which led to relinquishment of medical observation, especially in girls and young women, the birth the child with maternal PKU could be the result of that. 2. Introduction of colorimetric method improved the detecting of the mild PKU and hyperphenylalaninemia considerably.

[TSH levels in newborn with low and very low birth weight vs rescreening for congenital hypothyroidism]. / Analiza poziomów hormonu tyreotropowego u dzieci z niska i bardzo niska urodzeniowa masa ciala a celowosc przeprowadzenia powtórnego badania przesiewowego noworodków w kierunku wrodzonej niedoczynnosci tarczycy.

UNLABELLED: A disorder of thyroid function, as stated by various references, is very common among children with low and very low body weight. Also, the concentration of thyroid hormones in this group differs from that of neonates full term with the adequate body weight. In 1998, in southeastern Poland, a repeated screening for TSH level in blood spots on filter paper was introduced among neonates with low and very low birth-weight. The purpose of this work was the exclusion of late appearing transient hypothyroidism, as well as the verification of falsely positive results in the basic test. Newborns with low and very low birth-weight comprise nearly 5% of live births in the region. During 1998-2001, 4,445 children with body weight below 2500 g were tested. Tests for TSH level in blood on filter paper were carried out in neonates between three and six days of age and also at the end of the first month of life. TSH levels in blood on filter paper were estimated using the LIA method (Byk Sangtec Diagnostica). The results were divided into two groups: those with correct TSH, that is < 15 mIU/L, and those with a raised level 3 15 mIU/L. The repeated test confirmed the correct result in nearly 100% of the neonates, while in 20 (0.5%) showed the increase of TSH level above 15 mIU/L. TSH and fT4 monitoring followed by serum determinations during treatment showed primary hypothyroidism in 10 children and hyperthyrotropinemia in 5 cases. CONCLUSION: 1) It would appear advisable to introduce a repeated routine screening for hypothyroidism in the group of low and very low birth-weight neonates, as this permits the identification of cases with raised values requiring verification. 2) In addition, thanks to the repeated screening we avoid false negative pitfalls in low and very low birth-weight neonates, i.e. primary congenital and transient hypothyroidism.