Balascakova, M.

Camajova, J.

Holubova, A.

Kracmar, P.

Libik, M.

Macek, M.

Piskackova, T.

Skalicka, V.

Vavrova, V.

Votava, F.

Zemkova, D.

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12. Screening 
~ Newborn screening for CF in the Czech Republic: results from a 
pilot study 
A. Holubova 1 , F. Votava 2, V Skalicka 1, M. Balascakova 1 , V Vavrova 1 ,
D. Zemkova 1 , R Kracmar 2, M. Libik 1 , J. Camajova 1 , T. Piskackova 1 , M. Macek 
jr.1. 1 CF Centre, 2rid Sch. Medicine & UH Motol, 2Dept. Pediatrics, 3rd Sch. 
Medicine & UH K. Vinohrady, Prague, Czech Republic 
According to epidemiologic/genetic s udies the incidence of CF in our country is 
1:2700 newborns. Thus, given the current birthrate -35 new cases of CF should 
annually be detected. However, registry data demonstrated that 1/3 of CF patients 
remains clinically undiagnosed and that the age at diagnosis has markedly increased 
(prior to 1998 median: 0.58; between 1999~005:1.2 years). 
Therefore, in II/2006 we started two tier (IRT/DNA) pilot CF neonatal screening 
project (NSCF) comprising Bohemian regions, representing -2/3 of our population. 
Altogether 45,453 newborns were examined uring the initial 9 month period. In 
545 cases (1.2%), who had IRT concentration above the continuously adjusted cut 
off level, we examined the most common CFTR mutations. 
The diagnosis of CF was established in 5 newborns (2× F508del/F508del; 2× 
F508del/G551D; 1× F508del/Rl17H-7T mild CF) and these children were 
subsequently referred to CF Centres. Furthermore, we detected 42 newborns with 1 
CFTR allele (35× F508del, 2× CFTRdele2.3/21kb/, 2× N1303K, 1× G551D, 1× 
I507del and 1 × I148T). Until now 27 follow up sweat ests (ST) were performed 
(26× <30mmol/L, 1× 30 40mmol/L). IRT recall was carried out in 14 children 
with IRT > 200 ng/mL and with a non-detectable CFTR allele 11 children had 
negative IRT recall and 1 child was positive (ST negative). 
From these results the incidence of CF can preliminarily be adjusted to 1:9090 
newborns. However, these results can be skewed ue to lower number of newborns 
tested, effect of prenatal diagnosis and/or false negativity of NSCE 
Supported by IGA MZCR 8236 3, 00000064203 (6112) 
$103 
1~ Incidence of Cystic Fibrosis in high-risk Egyptian children and 
CFTR mutation analysis 
M.L. Naguib 1, I. Schrijver 2, R Gardner 3, L.M. Pique 2, S.S. Doss 1 , M.A. Abu 
Zekry 4, M. Aziz 5, S.Z. Nasr 6. 1Department ofPediatrics, Cairo University Faculty 
of Medicine, Egypt; 2Department ofPathology, 3Department ofMedicine, Stanford 
University School of Medicine, Stanford, CA, USA; 4Division of Pulmonology, 
Gastroenterology, 5Department of Clinical and Chemical Pathology, Cairo 
University Faculty of Medicine, Egypt; 6Department ofPediatrics, Division of 
Pulmonology, University of Michigan Medical Cente~ Ann Arbo~ MI, USA 
Background: Knowledge about Cystic Fibrosis (CF) in Egypt is limited. The 
objective of this study was to screen for CF in Egyptian children with suggestive 
clinical features and identify causative genetic mutations. 
Methods: Sixty-one patients from the Chest Unit, Cairo University Children's 
Hospital, Egypt, were included. Subjects presented with persistent or recurrent 
respiratory symptoms, failure to thrive, diarrhea nd/or steatorrhea and unexplained 
persistent jaundice. Patients were screened using the CF Indicator TM sweat test 
system (PolyChrome Medical, Inc, Brooklyn Ctr, MN). A quantitative sweat esting 
was conducted on 10 of 12 positive patients. Seven probands and one sibling 
underwent molecular analysis by direct DNA sequencing of the coding region and 
of the intronic sequences adjacent to the 27 exons of the CFTR gene. 
Results: Of 61 patients, 12 (20%) had positive sweat chloride screening. Ten 
of the 12 patients underwent quantitative sweat testing and were positive. Eight 
CFTR sequence changes were identified in seven affected probands and two were 
confirmed in one sibling by direct DNA sequencing 
Conclusion: The study results suggest hat CF is more common in Egypt than 
previously anticipated. Larger studies are warranted to identify the incidence, 
molecular basis and clinical pattern of CF in the Egyptian population. 
I •  Increased age at diagnosis justifies CF neonatal screening 
D. Zemkov{t 1 , V Skalick{t 1 , T. Ku~erovfi 1 , J. Barto~ovfi 1 , A. Holubova 1 ,
E Votava 2, M. Macek Jr. 1 , V Vfivrovfi 1 . 1CF Centre UHMotol, 2Dept. Pediatrics', 
UH K. Vinohrady, Charles Unia, Prague, Czech Republic 
CF care in Czech R. (CZ) has notably improved uring the past decade, with 
patient prognosis reaching that of other EU countries. On the other hand we are 
observing an increased number of late diagnoses. We assume that this is due to 
changes in postgraduate practician education within long-term health care system 
transformation. 
We analyzed age at diagnosis (ADG) in 357 patients clinically diagnosed before 
1998 and in 87 patients diagnosed between 1999~005. Before 1998 the median 
ADG was 0.58 years (60.2% of cases were diagnosed < 1 year), while after 1999 
the median ADG increased to 1.2 years (47.1% of cases were diagnosed by age 
1; p 0.036). Furthermore, increasingly patients are diagnosed between ages 2 and 
6 (27.6% vs. 16.5%; p 0.03). Although 45.8% of these patients are carriers of 
a Class IV-V ("mild") and/or unknown CFTR allele associated with pancreatic 
sufficiency, more than half of them diagnosed after the age of 2 years have pancreatic 
insufficiency (PI) and present with severe malnutrition/irreversible lung disease. 
Our longitudinally monitored patients with PI diagnosed after age 1 have poorer 
lung functions at the age of 8 years compared to those diagnosed before the age of 
1 year (FEV1 71.7±22.9 vs. FEV1 84.5±21.8%, predicted value; p 0.01). 
In the light of these observations we initiated in II/2005 pilot neonatal screening 
project comprising Bohemian regions of the CZ (2/3 of our population). We hope 
that it will help us to ascertain all CF infants with PI and most patients with mild 
CFTR alleles, and perhaps even older siblings with moderate disease phenotypes. 
Supported by MZCR 8236 3, 0064203 
1• Diagnosing and managing of Cystic Fibrosis patients in Western 
Ukraine 
H. Makukh 1, L. Bober 2, M. Tyrkus 1 , D. Zastavna 1 , O. Hnateiko 1 , O. Hinka 3, 
L. Chorna 1. 1Institute of Hereditary Pathology of Academy of Medical Science of 
Ukraine, 2Lviv Regional Specialized Children 2HosTital, 3Charity fund "DZVIN", 
Ukraine 
Every year about 250 Cystic Fibrosis (CF) children are expected to be born in 
Ukraine. There are differences between the CF patients' management possibilities 
in miscellaneous region of Ukraine. CFTR gene mutation analysis is performed in 
two centers only. Results of 10 years activities of non-formal Western Ukrainian 
CF team are examined. 
CFTR mutations are studied by PCR, RFLP, heteroduplex analysis, agarose or 
polyacrylamide g l electrophoresis. 
Since 1994 101 CF probands were detected. Eleven different CFTR gene mutations 
were found with the following frequencies: F508del (54.5%), W1282X (2.5%), 
CFTRdele2,3(21kb) (2.5%), N1303K (2.0%), G542X (2.0%), 1898 1G>A (1%), 
3849+10kbC>T (0.5%), R334W (0.5%), 2721de111 (0.5%), 1717 1G>A (0.5%), 
R553X(0.5%). Thirteen prenatal diagnostics were performed. Five cases of CF were 
confirmed. 
The evaluation of possible exocrine pancreatic nsufficiency is determined by faecal 
elastase-1 level which can also serve as a method for rapid and effective therapy 
adjustment in CF patients. 
CF patients, we monitor, receive ffective pancreatic enzymes, mucolytics, antibi- 
otic, bronchodilators, and individualized physiotherapy. Pancreatic enzymes only 
are free of charge for CF patients. Often patients have to pay the drugs costs of the 
themselves. 
The majority of patients are physically and socially adapted. We progress in de- 
creased of mortality rate and improved survival of CF patients. In 1997 association 
DZVIN was found by CF children parents. It renders ocial and psychological id 
for such families. 
In Ukraine adequate CF patients' healthcare requires creation of the CF National 
Program and regional CF centers. 


470 Newborn screening for CF in the Czech Republic: results from a pilot study 

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470 Newborn screening for CF in the Czech Republic: results from a pilot study

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