There is a widely accepted consensus on the benefits of newborn screening (NBS) for cystic fibrosis (CF) in terms of reduced disease severity, improved quality of life, lower treatment burden, and ...reduced costs. More and more countries in the world are introducing NBS for CF as a national preventive health program. Newborn screening for CF was introduced in the Republic of North Macedonia (RNM) in April, 2019, after a pilot study of 6 months in 2018. A two-step immunoreactive trysinogen (IRT-IRT) algorithm is performed, and then a sweat test for confirmation/exclusion of the CF diagnosis when the IRT values were both over the cutoff (70.0 and 45.0 ng/mL, respectively). In cases with confirmed diagnosis of CF (a sweat chloride concentration >60.0 mmol/L) or with intermediate sweat test results (a sweat chloride concentration of between 30.0 and 59.0 mmol/L), CF transmembrane conductance regulator (CFTR) mutation analysis is performed. By the end of 2020, over a period of 27 months, including the pilot study period, a total number of 43,139 newborns were screened for CF. Seventeen (0.039%) newborns were diagnosed with CF. In all newly discovered CF cases by screening, the diagnosis was confirmed by determination of the CFTR mutations. The most common CFTR mutation, F508del, was found with an overall incidence of 70.6%. Other more frequent mutations were G542X (11.8%) and N1303K (5.9%). Four mutations were found in one CFTR allele each: G1349D, G126D, 457TAT>G and CFTRdupexon22, with the last one being newly discovered with unknown consequences. An incredibly large difference was found in the incidence of the disease between the Macedonian and Albanian neonatal population, with almost four time higher prevalence among Albanians (1:4530
. 1:1284).
Objectives Due to the increased losses of chloride and sodium in the sweat, CF infants are predisposed to develop episodes of hyponatremic/hypochloremic dehydration with hypokalemia and metabolic ...alkalosis, the condition sometimes referred to as pseudo-Bartter's syndrome in CF. The aims of study were to estimate the prevalence of this metabolic disorder among CF infants in our region and the influence of some clinical and genetic factors on its developing. Methods The records of all 90 newly diagnosed infants with CF in the period from 1998 to 2014 were reviewed. Laboratory, clinical and CFTR genotype data of patients with pseudo-Bartter's syndrome were analyzed. Results Nineteen infants had manifestations of electrolyte depletion with metabolic alkalosis, therefore the prevalence of pseudo-Bartter's syndrome among newly diagnosed infants with CF was 21%. Mean age of patients was 4.2 months (range 1–8). Most of them were breastfed. Mean values of blood pH, serum bicarbonate, sodium, chloride and potassium (mmol/L) were: 7.57±0.06, 43.71±7.23, 118.2±4.98, 67.7±8.23 and 2.7±0.46, respectively. Concerning CFTR genotypes of these patients, a great variability was found: F508del/F508del (8), F508del/G542X (3), F508del/621+G→T (1), F508del/457TAT→G (1), F508del/711+3A→G (1), G126D/V456F (1), G126D/E585X (1), F508del/Unknown (2) and Unknown/Unknown (1). Five of them were pancreatic sufficient. Conclusion This metabolic disorder is a common presenting manifestation of CF in infancy in our region. The possibility of CF should be seriously considered in any infant with metabolic alkalosis and hypoelectrolytemia, whether or not there are associated pulmonary and/or gastrointestinal symptoms.
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