Supervisors info:
1. Λουκάς Ιωάννης, Αναπληρωτής Καθηγητής Φαρμακευτικής Χημείας
2. Παντερή Ειρήνη, Καθηγήτρια Φαρμακευτικής Χημείας
3. Ντότσικας Ιωάννης, Αναπληρωτής Καθηγητής του Τμήματος Φαρμακευτικής ΕΚΠΑ
Summary:
Newborn screening (NBS) is a health program, whose purpose is the early diagnosis of rare but at the same time life – threatening illnesses so that proper treatment can be applied , in order to ease and improve the quality of life of the newborn. In the present paper 1000 samples of newborn were studied, in which a biochemical control has been conducted for the detection not only of inborn errors of metabolism, but also of other genetic metabolic illnesses, which can be inherited with the autosomal recessive way. IEM includes fatty acid oxidation disorders, organic acid metabolic disorders and amino acid disorders, witch can be detected by tandem mass spectrometry (MS/MS). In case of a positive result, a second check is conducted to eliminate the possibility of a false positive result. However if a certain value remains in high levels, a urinal check can be conducted with the help of the GS/MS technique. Other general illnesses that have been examined with biochemical control were biotinidase deficiency (BTD), congenital adrenal hyperplasia (CAH) and cystic fibrosis (CF). The BTD deficiency can be detected with the help of colorimetric method. In the lab, a sample was detected with low levels of biotinidase activity. These levels indicated a carrier of the disease, so a blood plasma analysis followed, in order to be ascertained. In the case of CAH and CF, boxes of Delfia Neonatal kit have been used in order to determine the hormone 17-α-OH Progesterne (17-OHP) and pancreatic immunoreactive trypsinogen (IRT) respectively. Worthy to consider were three cases of positive samples, with the suspicion of being positive for the cystic fibrosis, because of the increased levels of IRT. A high quantity of IRT constitutes a good indication to detect carriers or diseased by cystic fibrosis. Therefore the conduction of a molecular control for the CFTR gene is necessary in order to assert whether we are dealing with a carrier or a diseased and by extension to determine which mutation is present in the 2 alleles, so that appropriate treatment can be applied. The molecular control has been conducted by the sequencing of the CFTR gene, applying the Sanger sequencing method. Two of the three samples that have been detected in the lab, were found to be carriers of the disease, since only one of the 2 alleles had a mutation in its sequence. Specifically they carried the F508del mutation, which is also the most common cause of cystic fibrosis. On the other hand the third sample was a case of compound heterozygote, which had 2 mutations, one being the common F508del and the other being the W1282X, each residing in one of the 2 alleles. The molecular control therefore, consists a very valuable tool, since its use can verify the existence of the disease, a suitable treatment can be applied and it can also give future parents the ability to know their genetic profile. This way, they will be informed whether they are carriers of a fatal disease, making them aware of the possibilities of transmitting it to their descendants. In conclusion we can realize not only the necessity and advantages of NBS in the biochemical and molecular sector, but also its ability to improve the life quality of the
diseased newborns.
Keywords:
Newborn screening (NBS), biochemical control, molecular control, Sanger sequencing, BTD deficiency, cystic fibrosis (CF), IRT, CFTR gene, F508del mutation, gene therapy.
