Mirela Tabaku

BACKGROUND Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in the glucosylceramidase beta 1 (GBA1) gene, with a wide range of clinical manifestations. Type 2 GD, the acute neuronopathic form, is the most severe and has historically been considered a distinct clinical entity. Emerging evidence suggests a broader phenotypic spectrum, including intermediate forms that do not fully align with the diagnostic criteria for either type 2 or type 3 GD. Here, we describe an Albanian patient with an unusual intermediate type 2-3 phenotype, homozygous for the rare GBA1 complex allele p.[His294Gln;Asp448His] that is frequently found in Balkan populations. Although this genotype is typically associated with early-onset type 2 GD and death within the first 2 years of life, our patient developed neurologic symptoms at 15 months and survived until age 5. CASE REPORT A male Albanian infant presented at 4 months of age with hepatosplenomegaly and thrombocytopenia. Genetic testing revealed homozygosity for the rare GBA1 complex allele p.[His294Gln;Asp448His]. Enzyme replacement therapy, initiated at 7 months, led to temporary improvement of visceral and hematological symptoms. Neurologic manifestations - including oculomotor apraxia, dystonia, and seizures - emerged at 15 months. Despite continued enzyme replacement therapy and supportive care, the patient's neurologic condition progressively worsened, and he died at age 5 due to disease progression and pulmonary complications. CONCLUSIONS This case reinforces the concept that type 2 GD exists on a phenotypic spectrum, rather than as a uniform clinical entity, and underscores the broad genotype-phenotype variability in GD.

Background/Objectives: Gaucher disease type 1 is an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the GBA1 gene. Although enzyme replacement therapy has improved patient outcomes, there is limited long-term real-world data on taliglucerase alfa. This study aimed to evaluate the long-term efficacy and safety of taliglucerase alfa in both treatment-naïve and previously treated patients with Gaucher disease type 1 over a 10-year period. Methods: This prospective, single-centre cohort study involved 29 patients (13 treatment-naïve and 16 previously treated with imiglucerase) who received taliglucerase alfa from 2015 to 2024. Clinical, hematological, visceral, skeletal, and biochemical parameters were assessed at baseline and at 12, 60, and 120 months. Biomarkers included chitotriosidase and glucosylsphingosine. Safety was evaluated through adverse event reporting and anti-drug antibody testing. Results: Hemoglobin and platelet counts improved or remained stable in all patients. By 60 months, liver volume had normalised in treatment-naïve patients (mean reduction: 23.1%), while spleen volume had decreased by up to 47.3%. Lyso-Gb1 levels decreased by 86.1% in patients who had not previously received treatment and by 59.5% overall, with a strong correlation to adherence. Bone mineral density improved in most cases. 137 adverse events were reported, 24% of which were mild infusion-related reactions. Anti-drug antibody developed in two patients, including one with a reduced therapeutic response. Conclusions: Taliglucerase alfa offers sustained long-term clinical, hematological and biochemical benefits in both treatment-naïve and previously treated Gaucher disease type 1 patients, with a favorable safety profile. Glucosylsphingosine proved to be a highly sensitive biomarker for monitoring therapeutic efficacy and detecting treatment response.

Background Rare diseases affect over 300 million people worldwide, with more than half of these cases presenting in childhood. Despite advances in genomic technologies, significant diagnostic delays remain, particularly in underrepresented populations. Although whole-genome sequencing is expected to be more effective than whole-exome sequencing, there are currently no direct patient-level comparisons from Albania. Methods We conducted a prospective, head-to-head comparison of whole-genome sequencing and whole-exome sequencing in 72 pediatric patients from Albania with suspected rare genetic disorders. Both technologies were applied in parallel using ISO-accredited pipelines. Variants were classified according to the ACMG guidelines and assessed for clinical relevance. Primary and secondary findings, as well as dual diagnoses, were recorded and compared. Results A molecular diagnosis was achieved in 72.2% of patients. Whole genome sequencing yielded diagnostic or secondary findings in 68.1% of cases, while whole exome sequencing identified primary diagnoses in 30.6% of cases. WGS made a primary diagnosis in 37.5% of cases, resolving complex or blended phenotypes and detecting variant types that were missed by WES, including deep intronic, regulatory and structural variants. Furthermore, WGS identified medically actionable secondary findings in 15.3% of patients, providing direct information for clinical management. Overall, WGS outperformed WES across variant classes and inheritance modes. Conclusion WGS demonstrated clear diagnostic superiority over WES in this pediatric cohort, particularly in identifying complex phenotypes and structural variants. These results suggest that WGS should be considered a primary diagnostic tool and highlight the importance of ensuring equitable access to genomic technologies for underrepresented populations.

Background: Retinoblastoma (RB), the most common intraocular cancer worldwide, has been extensively investigated. To the best of our knowledge, however, no reports exist on RB in Albania. We aimed to present the first case series of RB in Albania, including presentation, treatment, and outcome of patients. Materials and Methods: This was a retrospective case series of patients diagnosed with RB from 1998 to 2023 at a single country Mother Teresa University Hospital Center in Albania. Epidemiologic and clinical data were extracted from follow-up clinical charts. Results: During the 25-year study period, 22 patients were diagnosed with RB, of whom 59% were females. The average age at diagnosis was 21.8 months (SD—18.8 months). In 13 (59%) cases, the disease was diagnosed within the first year of life, and less than 5% were diagnosed after the age of 5 years. Overall, 18% of patients had family history of RB, and 41% had bilateral RB. The time from the first symptom to diagnosis was less than a month in 32% of cases, while 77% of patients were diagnosed within 4 months. The main presenting symptom was leukocoria in 6 (27%) cases, strabismus in 3 (14%) cases, and combination of both in 3 (14%) cases. Treatment was mainly a combination of enucleation and systemic chemotherapy in 15 (71%) cases. Only 13 (59%) patients continued treatment within Albania, with the rest being treated abroad. Conclusion: We present the first cohort of children with RB from Albania, a country with limited diagnostic and treatment resources. The advanced disease states of these children underscore the importance of implementing national pediatric screening programs. Cite this article as: Duka E, Hashorva E, Kapllanaj M, et al. Retinoblastoma in Albania: A 25-year retrospective analysis. Turk Arch Pediatr. 2025;60(2):159-163.

Background: Fructose‐1,6‐bisphosphatase (FBPase) deficiency is a rare autosomal recessive disorder of gluconeogenesis caused by biallelic pathogenic variants in the FBP1 gene. It presents with episodic hypoglycemia, lactic acidosis, and ketone body abnormalities, particularly during catabolic stress, but often mimics more common metabolic disorders, leading to diagnostic delays. Case Presentation: We describe the first genetically confirmed Albanian case of FBPase deficiency in a 3‐year‐old girl, born to nonsanguineous parents. The patient presented with recurrent episodes of vomiting, hypoglycemia, and metabolic decompensation since infancy. At her most severe presentation, she was admitted in a subcomatose state with profound hypoglycemia (35 mg/dL) and lactic acidosis (pH 6.9) without ketonuria. Whole exome sequencing identified a homozygous pathogenic FBP1 variant NM_000507.3(FBP1): c.472C > T; p. (Arg158Trp), a recurrent missense mutation associated with significant phenotypic variability. Parental testing confirmed autosomal recessive inheritance. Management and Outcome: Emergency management included intravenous dextrose and bicarbonate for metabolic acidosis, followed by nutritional interventions. The patient was advised to avoid fasting for more than 8 h and to limit fructose intake. No further metabolic crises were observed after these interventions. Conclusion: This case highlights the clinical and genetic complexity of FBPase deficiency and underlines the importance of genomic diagnostics in children with unexplained hypoglycemia and metabolic acidosis. Early diagnosis allows effective dietary management and prevents recurrent life‐threatening episodes. As the first reported case in Albania, it contributes to the growing recognition of FBPase deficiency as an underdiagnosed but treatable metabolic disorder.

Cite this article as: Bali D, Tabaku M, Gjikopulli A, et al. The first familiar case of PTEN-related disorder reported in Albania. Turk Arch Pediatr. 2023;58(5):559-561.

Tolectin is a non-steroid anti-inflammatory drug (NSAID) which has a clinically analgesic and antipyretic activity. Although the mechanism of its action is not known, tolectin inhibits prostaglandin synthetase in vitro and lowers the plasma level of prostaglandin E in humans. Recently, the anticancer effects of tolectin has been reported in in vitro studies. The aim of this study was to investigate the in vitro tolectin effects on antitumor TRP53 gene expression level in gastric adenocarcinoma cells. The gastric adenocarcinoma (AGS) cells were divided to control group and groups treated with 0.0012, 0.0023, 0.0049, 0.0097, 0.0194, 0.0389 mmol/mL. MTT assay method was used to determine the cell viability. Relative TRP53 gene expression level was evaluated by quantitative Real Time PCR. Data were analyzed using ANOVA and student’s t-test. Cell viability significantly decreased in all groups of tolectin treated AGS cells compared to control group; however, expression level of the TRP53 gene did not significantly changed in cells treated with effective concentration of tolectin (0.0131 mmol/mL) compared with control group. Our findings indicated that tolectin has a significant cytotoxic effects on gastric adenocarcinoma cells, however, its effective cytotoxic concentration has not significant impact on antitumor TRP53 gene expression level.

Autism spectrum disorder (ASD) is a very complex neurodevelopmental disorder whose symptomatology has been reported in several different genetic syndromes, one of which is Sotos syndrome. This syndrome is a congenital disorder, inherited autosomal dominant, being caused by a heterozygous pathogenic variant in the NSD1 gene or a deletion of this gene, which are present in more than 90% of individuals with this clinical diagnosis. We describe the case of a 13-year-old patient diagnosed with autism and Sotos syndrome. Objective. The description of this patient is intended to emphasize the importance of being aware in case of the co-association of ASD with one of the genetic syndromes, in the presence of clinical features not typical for both of them, in order to avoid delays in diagnosis. Conclusions. The late diagnosis of ASD and Sotos syndrome in our patient also leads us to the conclusion that, in cases of speech and communication delays in children, it is necessary to carry out a careful examination and a detailed assessment of the child’s development, including experts such as pediatricians development, child psychiatrists, geneticists, speech therapists etc. This will help to establish an early diagnosis, which is important for the development of follow-up, coordination of multidisciplinary care, treatment and prognosis.