Assessment of Pathogenic Variants in the PAH Gene and Genotype-Phenotype Correlation in Phenylketonuria Patients from Turkey.

This study aims to determine the allele and genotype frequency, evaluate genotype-phenotype correlation and contribute to the spectrum of pathogenic variants in the PAH gene. Ninety-three individuals diagnosed with PKU were included in the study. Next-generation sequencing was utilized for detecting variants in the PAH gene. Copy Number Variations in patients without biallelic pathogenic variant were investigated by Multiplex Ligation-dependent Probe Amplification method. Genotype-phenotype correlations and genotype-based phenotype predictions were examined by comparing molecular test results with BIOPKUdb database. The clinical distributions of the patients were as follows: classic PKU 21% (n = 19), mild PKU 3% (n = 3), and mild hyperphenylalaninemia 76% (n = 71), respectively. Thirty-nine distinct variants and 70 distinct genotypes were found in patients. The most frequently observed variant was p.(Ala300Ser) (13.9%) and the most frequently observed genotype was p.[Ala300Ser];[Ala300Ser] (5.6%). Compound heterozygous genotypes (%69) were more prevalent than homozygous genotypes. A novel variant, c.441+4A>C, was observed. Predicted metabolic phenotypes in the database showed consistency with patient phenotypes (n = 33/41). BH4 responsiveness showed partial consistency with database predictions (n = 13/25). Establishing genotype-phenotype correlations can facilitate personalized management approaches. Overall, this study contributes to understanding the genetic basis and clinical course of PKU.

Delays in Newborn Screening for Phenylketonuria from Birth to Diagnosis and Factors Affecting This.

This study aims to evaluate the process of neonatal phenylketonuria (PKU) screening from birth to admission to the pediatric metabolism polyclinic, determining delays in the screening program and the factors influencing them. This study was conducted during 2021-2023. Blood collection dates, results, and probable parameters causing delays in the screening program were recorded. This study included 118 infants. Admission time to the polyclinic was (mean ± SD) 25.2 ± 12.6 days (min-max: 3.4-78.9 days). Admission time was significantly high for refugees, those whose parents were consanguineous, and those who had more heel-prick blood samples taken (p < 0.001, p = 0.005, and p < 0.001, respectively). The first heel-prick blood phenylalanine (phe) level was significantly negatively correlated with the admission time (p < 0.001). Patients' admission time whose first blood phe level < 240 µmol/L was statistically significantly higher than in those with ≥240 µmol/L (p < 0.001). We determined that there were delays in PKU screening from birth to admission to the polyclinic. Being a refugee, the presence of consanguineous marriages, the increase in the number of heel-prick tests, and blood phe levels at a range of 120-240 µmol/L were the factors that played a role in this delay. Taking steps to reduce the impact of these parameters can prevent delays in newborn PKU screening and increase the success of the screening program.

Inherited Metabolic Diseases from Past to Present: A Bibliometric Analysis (1968-2023).

Bibliometric studies on inherited metabolic diseases (IMDs) do not exist in the literature. Therefore, our research aims to conduct a bibliometric study to determine the current status, trending topics, and missing points of publications on IMDs. Between 1968 and 2023, we conducted a literature search with the keyword "inherited metabolic disease" in the SCOPUS database. We included research articles in medicine written in English and published in the final section. We created our data pool using VOSviewer, SciMAT, and Rstudio software programs for the bibliometric parameters of the articles that met the inclusion criteria. We performed a bibliometric analysis of the data with the R package "bibliometrix" and BibExcel programs. We included 2702 research articles published on IMDs. The top three countries that have written the most articles in this field are the USA (n = 501), the United Kingdom (n = 182), and China (n = 172). The most preferred keywords by the authors were: newborn screening (n = 54), mutation (n = 43), phenylketonuria (n = 42), children (n = 35), genetics (n = 34), and maple syrup urine disease (n = 32). Trending topics were osteoporosis, computed tomography, bone marrow transplantation in the early years of the study, chronic kidney disease, urea cycle disorders, next-generation sequencing, newborn screening, and familial hypercholesterolemia in the final years of the study. This study provides clinicians with a new perspective, showing that molecular and genetic studies of inherited metabolic diseases will play an essential role in diagnosis and treatment in the future.

Evaluation of growth in children and adolescents after renal transplantation.

Büyükkaragöz B, Bakkaloglu SA, Tuncel AF, Kadioglu-Yilmaz B, Karcaaltincaba D, Pasaoglu H. Evaluation of growth in children and adolescents after renal transplantation. Turk J Pediatr 2019; 61: 217-227. Despite the advances in the last decades, it is well-known that optimal growth is usually not achieved in children with chronic kidney disease (CKD) even after successful renal transplantation (RTx). In this study, our aim was to evaluate growth patterns and factors affecting growth in pediatric and adolescent renal transplant recipients (RTR). Thirty-seven prevalent RTR with mean age of 17.0±2.9 years and mean post-RTx duration of 4.2±2.0 years were evaluated. Growth parameters, height velocities and factors affecting growth at the time of RTx (baseline) and in the post-RTx follow-up were also retrospectively assessed. Cumulative corticosteroid (CS) doses were calculated. Mean height and weight standard deviation score (SDS) values were negative (-1.4±1.1 and -1.2±1.5, respectively), whereas height SDS was positive in 16% of the patients. Mean weight, height, and BMI (body mass index) SDS of the RTR were significantly higher than the values at transplantation (p < 0.001 for weight and height SDS; p < 0.05 for BMI SDS). Height SDS was < -2.0 in 19% of the patients while 60% at the baseline. Main factors associated with post-RTx height SDS were pre-RTx height SDS (B: 0.448, p < 0.01) and CKD duration (B: -0.01, p < 0.05). Although it was much better than the pre-RTx period, the present study reveals that post- RTx growth was less than anticipated. As well as minimizing post-RTx CS doses and preserving graft function in the post-RTx follow-up, performing early transplantation and all efforts for minimizing pre-RTx growth deficit are crucial for an optimal post-RTx growth.