A comprehensive integrated disease management program for phenylketonuria (IDMP-PKU) from Türkiye: rationale, design and patient characteristics
Abstract Background Phenylketonuria is an autosomal recessive disorder characterized by the deficiency of phenylalanine hydroxylase, which converts phenylalanine into tyrosine. Diagnosis and prompt initiation of appropriate treatment shortly after birth are important for achieving optimal outcomes i...
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2025-08-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03702-7 |
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| author | Mehmet Cihan Balci Deniz Kor Yilmaz Yildiz Meryem Karaca Fatma Derya Bulut Ayca Burcu Kahraman Alihan Yesil Ezgi Burgac Kismet Ciki Arzu Selamioglu Burcu Koseci Asli Durmus Irem Kaplan Esra Kara Halise Neslihan Mungan Serap Sivri Gulden Fatma Gokcay Aysegul Tokatli Mubeccel Demirkol Turgay Coskun Imran Ozalp |
| author_facet | Mehmet Cihan Balci Deniz Kor Yilmaz Yildiz Meryem Karaca Fatma Derya Bulut Ayca Burcu Kahraman Alihan Yesil Ezgi Burgac Kismet Ciki Arzu Selamioglu Burcu Koseci Asli Durmus Irem Kaplan Esra Kara Halise Neslihan Mungan Serap Sivri Gulden Fatma Gokcay Aysegul Tokatli Mubeccel Demirkol Turgay Coskun Imran Ozalp |
| author_sort | Mehmet Cihan Balci |
| collection | DOAJ |
| description | Abstract Background Phenylketonuria is an autosomal recessive disorder characterized by the deficiency of phenylalanine hydroxylase, which converts phenylalanine into tyrosine. Diagnosis and prompt initiation of appropriate treatment shortly after birth are important for achieving optimal outcomes in phenylketonuria. IDMP-PKU is an ongoing study to gain insight into the patient journey and identify the unmet needs and areas for improvement in diagnosis, treatment, and follow-up of PKU in Türkiye. Aim To present the rationale and design of the IDMP-PKU study, as well as the findings from an interim analysis, describing baseline demographic, diagnosis, family history, and genetic testing data for 1553 children enrolled in the study. Method This is a multicenter, observational registry-based study, conducted in 3 tertiary pediatric metabolic clinics in Türkiye. The study provides a descriptive analysis of baseline demographic, diagnosis, family history, and genetic testing data of study population. Results The study included 1,553 patients (median age: 10 (IQR 5–18) years; 37.1% classical PKU) from 90% of the cities in Türkiye, diagnosed between 1981 and 2022. Parental consanguinity was reported in 43.5% of families (27.1% first cousins). The most frequently detected allelic variant was c.1066-11G > A (IVS-10-11G > A) (22.8%). Homozygous mutations were more common in patients with parental consanguinity (76.8% vs 17.1%; p < 0.001). The median time to diagnosis improved to 21 days after the implementation of the national newborn screening (NBS) program in December 2006 but 28.6% of patients were diagnosed after one month of age. Low level of maternal education was associated with longer time to diagnosis (p < 0.001). Conclusions Implementation of national NBS has contributed to earlier identification of patients with PKU. Increasing the number of screening laboratories and pediatric metabolic clinics will speed up the diagnostic process and help achieve the guideline-recommended time for diagnosis and initiation of treatment. In countries with high rates of consanguineous marriages, increasing public awareness of PKU and genetic counselling before marriage will be valuable in reducing the prevalence of PKU. |
| format | Article |
| id | doaj-art-60147a65d2a14cfb95f6fbc775f737ed |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-60147a65d2a14cfb95f6fbc775f737ed2025-08-20T03:46:12ZengBMCOrphanet Journal of Rare Diseases1750-11722025-08-0120111110.1186/s13023-025-03702-7A comprehensive integrated disease management program for phenylketonuria (IDMP-PKU) from Türkiye: rationale, design and patient characteristicsMehmet Cihan Balci0Deniz Kor1Yilmaz Yildiz2Meryem Karaca3Fatma Derya Bulut4Ayca Burcu Kahraman5Alihan Yesil6Ezgi Burgac7Kismet Ciki8Arzu Selamioglu9Burcu Koseci10Asli Durmus11Irem Kaplan12Esra Kara13Halise Neslihan Mungan14Serap Sivri15Gulden Fatma Gokcay16Aysegul Tokatli17Mubeccel Demirkol18Turgay Coskun19Imran Ozalp20Division of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Children’s Hospital, Istanbul UniversityDivision of Pediatric Metabolism and Nutrition, Department of Pediatrics, Faculty of Medicine, Cukurova UniversityDivision of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe UniversityDivision of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Children’s Hospital, Istanbul UniversityDivision of Pediatric Metabolism and Nutrition, Department of Pediatrics, Faculty of Medicine, Cukurova UniversityDivision of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe UniversityDivision of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Children’s Hospital, Istanbul UniversityDivision of Pediatric Metabolism and Nutrition, Department of Pediatrics, Faculty of Medicine, Cukurova UniversityDivision of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe UniversityDivision of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Children’s Hospital, Istanbul UniversityDivision of Pediatric Metabolism and Nutrition, Department of Pediatrics, Faculty of Medicine, Cukurova UniversityDivision of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Children’s Hospital, Istanbul UniversityDivision of Pediatric Metabolism and Nutrition, Department of Pediatrics, Faculty of Medicine, Cukurova UniversityDivision of Pediatric Metabolism and Nutrition, Department of Pediatrics, Faculty of Medicine, Cukurova UniversityDivision of Pediatric Metabolism and Nutrition, Department of Pediatrics, Faculty of Medicine, Cukurova UniversityDivision of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe UniversityDivision of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Children’s Hospital, Istanbul UniversityDivision of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe UniversityDivision of Pediatric Nutrition and Metabolism, Istanbul Medical Faculty, Children’s Hospital, Istanbul UniversityDivision of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe UniversityDivision of Pediatric Metabolism, Department of Pediatrics, Faculty of Medicine, Hacettepe UniversityAbstract Background Phenylketonuria is an autosomal recessive disorder characterized by the deficiency of phenylalanine hydroxylase, which converts phenylalanine into tyrosine. Diagnosis and prompt initiation of appropriate treatment shortly after birth are important for achieving optimal outcomes in phenylketonuria. IDMP-PKU is an ongoing study to gain insight into the patient journey and identify the unmet needs and areas for improvement in diagnosis, treatment, and follow-up of PKU in Türkiye. Aim To present the rationale and design of the IDMP-PKU study, as well as the findings from an interim analysis, describing baseline demographic, diagnosis, family history, and genetic testing data for 1553 children enrolled in the study. Method This is a multicenter, observational registry-based study, conducted in 3 tertiary pediatric metabolic clinics in Türkiye. The study provides a descriptive analysis of baseline demographic, diagnosis, family history, and genetic testing data of study population. Results The study included 1,553 patients (median age: 10 (IQR 5–18) years; 37.1% classical PKU) from 90% of the cities in Türkiye, diagnosed between 1981 and 2022. Parental consanguinity was reported in 43.5% of families (27.1% first cousins). The most frequently detected allelic variant was c.1066-11G > A (IVS-10-11G > A) (22.8%). Homozygous mutations were more common in patients with parental consanguinity (76.8% vs 17.1%; p < 0.001). The median time to diagnosis improved to 21 days after the implementation of the national newborn screening (NBS) program in December 2006 but 28.6% of patients were diagnosed after one month of age. Low level of maternal education was associated with longer time to diagnosis (p < 0.001). Conclusions Implementation of national NBS has contributed to earlier identification of patients with PKU. Increasing the number of screening laboratories and pediatric metabolic clinics will speed up the diagnostic process and help achieve the guideline-recommended time for diagnosis and initiation of treatment. In countries with high rates of consanguineous marriages, increasing public awareness of PKU and genetic counselling before marriage will be valuable in reducing the prevalence of PKU.https://doi.org/10.1186/s13023-025-03702-7PhenylketonuriaNewborn screeningDiagnosisAllelic variantConsanguinityMaternal education |
| spellingShingle | Mehmet Cihan Balci Deniz Kor Yilmaz Yildiz Meryem Karaca Fatma Derya Bulut Ayca Burcu Kahraman Alihan Yesil Ezgi Burgac Kismet Ciki Arzu Selamioglu Burcu Koseci Asli Durmus Irem Kaplan Esra Kara Halise Neslihan Mungan Serap Sivri Gulden Fatma Gokcay Aysegul Tokatli Mubeccel Demirkol Turgay Coskun Imran Ozalp A comprehensive integrated disease management program for phenylketonuria (IDMP-PKU) from Türkiye: rationale, design and patient characteristics Orphanet Journal of Rare Diseases Phenylketonuria Newborn screening Diagnosis Allelic variant Consanguinity Maternal education |
| title | A comprehensive integrated disease management program for phenylketonuria (IDMP-PKU) from Türkiye: rationale, design and patient characteristics |
| title_full | A comprehensive integrated disease management program for phenylketonuria (IDMP-PKU) from Türkiye: rationale, design and patient characteristics |
| title_fullStr | A comprehensive integrated disease management program for phenylketonuria (IDMP-PKU) from Türkiye: rationale, design and patient characteristics |
| title_full_unstemmed | A comprehensive integrated disease management program for phenylketonuria (IDMP-PKU) from Türkiye: rationale, design and patient characteristics |
| title_short | A comprehensive integrated disease management program for phenylketonuria (IDMP-PKU) from Türkiye: rationale, design and patient characteristics |
| title_sort | comprehensive integrated disease management program for phenylketonuria idmp pku from turkiye rationale design and patient characteristics |
| topic | Phenylketonuria Newborn screening Diagnosis Allelic variant Consanguinity Maternal education |
| url | https://doi.org/10.1186/s13023-025-03702-7 |
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