1. SCREENING FOR CONGENITAL HYPOTHYROIDISM AND PHENYLKETONURIA IN MURES COUNTY -RESULTS AND FOLLOW-UP- Author: Dr. Campean Cristina Coordinators: Conf. Dr. Pascanu Ionela Asist univ. Dr. Pitea Ana Maria

2. BACKGROUND  A national screening program for congenital hypothyroidism (CHT) and Phenylketonuria (PKU) was started in 2009.  CHT -the most frequent endocrine disease in children.  Neurologic, motor and growth deficiencies  Mental retardation.  The prevalence of CHT: 1:4000 newborns

3. BACKGROUND  PKU  Metabolic disease  Enzimatic deficiency (phenylalanine hidroxilase)  Severe psycho-neurological retardation.  The prevalence of PKU - 1:3000-1:30000 in Europe

4. HYPOTHYROIDISM- SIGNS AND SYMPTOMS Hypotonic posture Myxedematous facies Macroglossia Umbilical hernia Poor feeding and growth Constipation Prolonged jaundice Hoarse cry Hypothermia astogi and LaFranchi Orphanet Journal of Rare Diseases 2010 5:17

5. PKU- SIGNS AND SYMPTOMS  Mental retardation  Epilepsy  Stunted growth  Eczema  Microcephaly  Musty odor  Fair skin and hair, blue eyes

6. OBJECTIVES  Evaluation of the results of the screening program for CHT and PKU in Mures county.  Follow-up of confirmed cases.

7. METHODS  The study included all children born in the 8 maternities in Mures County screened for CHT and PKU from 2009-2013.  The levels of thyroid stimulating hormone (TSH) and phenylalanine (Phe)- fluorometric assay.  TSH >10 µUI/L, Phe > 3 mg/dl  Retested

8. METHODS  Screening procedure: (Day2-4)  Capillary blood sample from the heel „heel stick procedure”  Filter paper   Laboratory  TSH>10mU/l/Phe>3mg/dl  Public health authority  Endocrinologist, Pediatrician  Family of the newborn  Retrospective study: Screening data from the public health authority / CHT pacients - Endocrinology clinic/ PKU pacients-Pediatrics I clinic

9. RESULTS YEAR20092010201120122013TOTAL NEWBORNS5720561658795822568328720 TESTED1788551655035716562824151 % TESTED 31%98%93%98%99%84% CHT POSITIVE SCREENING -975728 CHT CONFIRMED CASES -11316 PKU POSITIVE SCREENING 123118 PKU CONFIRMED CASES 121116 Prevalence 1:4.025 for PKU and CHT 84% of newborns were screened(97% between 2010-2013) 21% of positive CHT screening cases were confirmed, 75% for PKU

10. NameScreening ConfirmationData/ valoare03.201205.201207.201208.201201.2014 P. Maria9,1 mg/dl10,1 mg% 31.01.2012 Phe serica 14,4 mg/dl - cantitativ 10,98 mg/dl 14.03.2012 1,3 mg% - 08.08.2012 1,3 mg% M. Ioan32 mg% 31.01.2012 semicantitativ 14,5 mg/dl - cantitativ 5,9 mg/dl 14.05 2012 12 mg% S. Brigitta >3mg% 14.05 2012 1,8 mg% A. Szilard >3mg% S. Tudor>3 mg%7,4 mg% 09.07.2012 9 mg% 31.07.2012 1,1 mg% 22.01.2014 2.4 mg% C. Adina13.4mg %15.9 mg%2013 30.04.2013 35.0 mg% 22.05.2013 13.0 mg% 12.06.2013 5.0 mg%

11. Name Date of birth TSH value at screening TSH uUI/ml / FT4 ng/dl (vn:0,38-4,31 µUI/ml) F.A. 07 09 2010 163 Repeated 176 27 07 2011 TSH: 54.35 FT4: 0.97 21 05 2012 TSH 188.43 FT4: 0.19 22 08 2012 TSH 77.33 FT4 1.25 23 05 2013 TSH: 41.8 FT4: 1.22 19 03 2014 TSH: 15.1 FT4: 1.09 L.A. 25 08 2011 18.68 Repeated 27.7 21 09 2011 TSH: 13.21 FT4:1.43 G.S. 18 08 2012 22 uuI/ml 21 repetat 15 10 2012 TSH: 3.26 FT4: 1.1 L.L. 10 09 201215 uuI/ml 19 10 2012 TSH: 5.24 FT4: 1.14 C.C16 12 201121 Repeated 19.4 06 01 2012 TSH 6.63 FT4 2.08 K.A.06 01 201330.49 Repeated 22.33 18 02 2013 TSH: 15.95 FT4: 17.24

12. DISCUSSION  CHT PREVALENCE CountryPrevalence Austria1:2927 Belarus1:9507 France1:2848 Germany1:2955 Hungary1:2207 Italy1:1748 Russia1:3102 Estonia1:13886 PKU PREVALENCE CountryPrevalence Austria1:7902 Bulgaria1:33266 France1:17769 Germany1:8553 Hungary1:12689 Italy1:3654 Russia1:7714 Slovenia1:3042 Prevalence 1:4.025 both for PKU and CHT NE Romania 1: 8478 for CHT, and 1: 15261 for PKU.(72% of newborns tested) J. Gerard Loebe, Neonatal screening in Europe; the situation in 2004, J Inherit Metab Dis Newborn screening for rare diseases in the north-east part of Romania: results of the newborn screening program 2009-2012 D. Anton-Paduraru1, M.Iliescu2

13. DISCUSSION  PKU therapy: control of ingested Phe (maintaining a level of Phe between 2-6 mg/dl )  The diet(and level of Phe ingested) must be individualised  The diet should be initiated in the first 20 days after birth  The age at which the diet is initiated and the metabolic control level influence the outcome

14. DISCUSSION Special diet products for PKU  Milk formula (Phe-free aa, plant and animal fats, carbohidrates, vitamins, fibres)  Proteic substituent (Phe-free aa)  Special diet products - aproteic  Cooking powder(flour) - rice replacer  Egg replacer - aproteic pasta  Aproteic biscuits - aproteic cereals

15. DISCUSSION  The treatment for CHT :  Levothyroxine  Starting dose :10-15 μg/kg  Cognitive development is normalized if the treatment is administered early (first 2 weeks after birth)

16. DISCUSSION Why are there so many unconfirmed CHT cases?  Some infants tested before day 3 after birth (early discharge )  Prematurity and ilnesses Why aren’t all newborns tested? - Some newborns die before being tested - Parents refuse - Omission by medical staff

17. DISCUSSION  Cost-efficiency?  Screening tests - free of charge for all newborn  Cost (3 euro/test) - National Health Program for Neonatal Screening.  24151 nn tested x3Euro=72453 Euro/ 12= 6037.75 Euro/confirmed CHT/PKU case.  Early treatment reduces disease complications  reduced costs for short- and long-term care.

18. CONCLUSIONS  Screening for PKU and HTC  important health program  early diagnosis of diseases with severe consequences.  97% of newborns were screened between 2010-2013.  6 cases of CHT and 6 cases of PKU were confirmed.  There are problems in the further management of confirmed cases: some parents refuse to accept the diagnosis and treatment (PKU)/ they don’t comply to the treatment/ don’t attend mandatory controls

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