Tethered spinal cord syndrome is a neurological disorder caused by tissue attachments that limit the movement of the spinal cord within the spinal column. Attachments may occur congenitally at the base of the spinal cord (medullary cone) or they may develop near the site of an injury to the spinal cord. These attachments cause an abnormal stretching of the spinal cord. The course of the disorder is progressive. We present two patients that were diagnosed at age of three months and three years, respectively. Final diagnosis was made by magnetic resonance imaging, and both patients were referred to University Clinic of Neurosurgery for further treatment. Our aim is to illustrate the advantages of the early diagnostics of this progressive condition, to present diagnostic methods that are age-dependent and to illustrate the early clinical indicators for its existence.

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 vs. 1:1284).

Background:Achondroplasia is a skeletal dysplasia, the most common cause of rhizomelic dwarfism.Case presentation:This is a ten year old boy who was first diagnosed prenatally. He had a mutation c1138G>A in the gene FGFR3 in a heterozygotic constellation. His IGF1 and IGFBP3 levels were normal. Two stimulation tests for growth hormone were performed with values within the reference range. His psychomotor development was adequate for his age except for speech difficulty. He started with recombinant hGH (r-hGH) at the age of 3.4 years in a dose of 0.06 mg/kg. His mean Height SDS (HtSDS) was -2.2.Results:The growth increased to 10 cm/year in the first year of therapy (HtSDS -1.1). It decreased during the second year to 4 cm (HtSDS -1.7) and again increased during the third year to 8 cm/year (HtSDS–1.3). In the next years the growth was constant (6.5, 2.3, 3.5 cm / year). He is still growing in the 3rd percentile of the growth curve (HtSDS – 1.2) under GH treatment. The body disproportion remained the same.Conclusion:The growth response on GH treatment was satisfactory in the first 4 years of treatment, and the boy still continued to grow. The young age at the start of treatment was also of importance. Our other patients with achondroplasia who started treatment older had a poor response to growth hormone.

Benign transient hyperphosphatasemia (BTH) is a condition which occurs in children younger than five years, characterized by a complete absence of specific clinical and laboratory findings of bone or liver diseases and a five or even 20–70-fold increase in serum of alkaline phosphatase levels(ALP). The aim of this case report was to point out that elevated levels of ALP are not always related to serious bone and liver diseases. We described three healthy patients, which were referred to our out-patient clinic by their primary care physicians because of markedly elevated levels of ALP. The diagnosis of BTH was based on a thorough physical exam, a wide range of laboratory and imaging tests, which excluded liver or bone disease as a cause for elevated ALP. BTH is not very well-known and managed in daily clinical practice. Primary care physicians should consider this diagnosis in cases with elevated ALP in otherwise healthy infants and toddlers, refrain from unnecessary tests, prescribing higher doses of vitamin D3 or referral to tertiary level pediatric institutions.

Micromastia or breast hypoplasia is described as underdevelopment of a woman’s mammary tissue. We present the case of a 15-year-old girl with unilateral micromastia, with familial predisposition. Ultrasound, hormonal, dysmorphic, cardiologic, genetic examinations and testing were performed. No mutation in the whole- exome sequencing was found, nor novel mutation. Some of these cases have been reported to be related to breаst cancer so further follow-up is mandatory. Therapy consists of surgical reconstruction of the affected breast. This is a rare condition and it requires a multidisciplinary approach.