GM1-gangliosidosis (MIM# 230500) and mucopolysaccharidosis IVВ (Morquio B, MIM# 230500) are autosomal-recessive diseases, which belong to the group of lysosomal storage disorders and are caused by changes in the structure of the same gene, GLB1. The mutations in GLB1 lead to deficiency in acid β-galactosidase, and, as a result, the accumulation of GM1-gangliosidosis and keratan sulphate in the patients' lysosomes. Aim. To analyze the spectrum of mutations in GLB1 in Ukrainian patients with GM1 gangliosidosis and Morquio B disease. Results. We analyzed GLB1 in 25 Ukrainian patients with the diagnosis of GM1-gangliosidosis and one patient with Morquio B disease; 52 alleles were analyzed. Seventeen types of pathogenic mutations were identified, including 11 missense replacements, three deletions, one insertion and two mutations in the splicing site. The missense mutation p.His281Tyr (c.841C>T) in exon 8 was found to be the most common, as it was found in 19 out of 52 mutant alleles (36.5 %) of all the examined patients. The study allowed to identify six new mutations, which had not been found in any databases or previously described in scientific literature, including three deletions (c.699delG, c.833delG, c.1203_1205delTTA), two missense replacements (p. Gly243Arg, p.Gly262Ala) and one mutation in the splicing site (IVS12+8T>C). Conclusions. Our results can be used for a precise molecular diagnostics of patients with GM1-gangliosidosis and Morquio B disease and prenatal diagnostics in the high risk families. K e y w o r d s: GM1-gangliosidosis, Morquio B disease, gene GLB1.

Ukraine’s healthcare system shows remarkable resilience in continuing newborn screening (NBS) program, beyond war challenges. Amid the conflict, a Ukrainian newborn screened positive for an extremely rare severe combined immunodeficiency (SCID) —purine nucleoside phosphorylase (PNP) deficiency. Ukraine successfully carried out NBS on neonatal dried blood spot (DBS) by real-time PCR, which showed remarkably reduced T-cell receptor and kappa-deleting recombination excision circles (TREC/KREC). Retesting was delayed due to difficult communication with the family. Whole exome sequencing on a new DBS confirmed the diagnosis. The newborn was candidate for al-logeneic hematopoietic stem cell transplantation (HSCT), the only curative treatment. HSCT is a complex procedure still ongoing in Ukraine despite the conflict. However, due to the psychosocial strain, the family sought medical support in Germany, where HSCT was performed successfully at 6 months. As part of a collaborative initiative with Italy, PNP biomarkers were quantified on the same DBSs using tandem mass spectrometry, according to the protocols established for SCID NBS in Tuscany, serving as a proof of concept of its diagnostic performance. This case highlights the importance of sustaining preventive and life-saving healthcare services, and reflects the key role of international partnerships in upholding the right to healthcare in times of crisis.

Mutation analysis of gene GLB1 in 26 patients from different regions of Ukraine diagnosed with GM1-gangliosidosis identified 15 pathogenic mutations. The most common was missense mutation p.His281Tyr (c.841C>T) in exon 8, which was found in at least one allele in 16 of 26 patients (61.5%), accounting for 20 of 52 (38.5%) mutant alleles. Mutation p.His281Tyr (c.841C>T) was described in rare cases in patients from Germany, Italy, and Portugal, while no alleles with such a replacement were found in other countries. This may indicate a much higher frequency of this mutation in Ukraine compared to other countries. Analysis of the information about the spatial distribution of the families with mutation p.His281Tyr (c.841C>T) revealed that most of the alleles with this mutation (14 of 20 or 70%) were found in patients from the western regions of the country, which may be due to the founder effect.

The neuronal ceroid lipofuscinosis type 2 (CLN2) is a heterogeneous group of neurodegenerative lysosomal storage disorders caused by autosomal recessive inheritance of two pathogenic variants in trans in the TPP1 gene. Classical late‐infantile CLN2 disease has a very well‐defined natural history. However, a small number of patients with TPP1 enzyme deficiency present a later onset or protracted disease course within this group there are phenotypic variants. Our work aimed to identify pathological variants in the TPP1 gene that conditioned the development of CLN2 disease in Ukrainian patients, to compare these variants with those found in patients from other European and non‐European regions, and to make genotype–phenotype associations for this disease. The phenotypes and genotypes of the 48 CLN2‐affected individuals belonging to 43 families were profiled through clinical data collection, enzyme analysis, and genotyping. In most patients, genotype and phenotype correlation are in keeping with the data of previous studies. The clinical signs of the disease in patients with new, previously undescribed variants, allowed us to augment existing data about genotype–phenotype correlations for CLN2 disease. The combination of genotype and clinical form of the disease demonstrated that predicting the type and clinical course of the disease based on genotype is very complicated. The data we obtained supplements existing information on genotype–phenotypic correlations in this rare disease, which, in turn, lays the foundation for a personalized approach to the management of this disease.

Ukraine’s healthcare system has shown remarkable resilience in continuing newborn screening (NBS), beyond the challenges of war. Amid the conflict, a Ukrainian newborn screened positive for an extremely rare severe combined immunodeficiency (SCID)–purine nucleoside phosphorylase (PNP) deficiency. Ukraine successfully carried out NBS on a neonatal dried blood spot (DBS) by real-time PCR, which showed remarkably reduced T-cell receptor and kappa-deleting recombination excision circles (TREC/KREC). Retesting was delayed due to communication difficulties with the family. Whole exome sequencing on a new DBS confirmed the diagnosis. The newborn was a candidate for allogeneic hematopoietic stem cell transplantation (HSCT), the only curative treatment. HSCT is a complex procedure still ongoing in Ukraine despite the conflict. However, due to the psychosocial strain, the family sought medical support in Germany, where HSCT was performed successfully at 6 months. As part of a collaborative initiative with Italy, PNP biomarkers were quantified on the same DBSs using tandem mass spectrometry, according to the protocols established for SCID NBS in Tuscany, serving as a proof of concept of its diagnostic performance. This case highlights the importance of sustaining preventive and life-saving healthcare services, and reflects the key role of international partnerships in upholding the right to healthcare in times of crisis.