دورية أكاديمية
Genetic etiology and clinical challenges of phenylketonuria.
| العنوان: | Genetic etiology and clinical challenges of phenylketonuria. |
|---|---|
| المؤلفون: | Elhawary NA; Department of Medical Genetics, College of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi Arabia. naelhawary@uqu.edu.sa., AlJahdali IA; Department of Community Medicine, College of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi Arabia., Abumansour IS; Department of Medical Genetics, College of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi Arabia., Elhawary EN; Faculty of Medicine, MS Genomic Medicine Program, University of Southampton, Southampton General Hospital, Southampton, UK., Gaboon N; Department of Clinical Genetics, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Dandini M; Department of Laboratory and Blood Bank, Maternity and Children Hospital, Mecca, Saudi Arabia., Madkhali A; Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia., Alosaimi W; Department of Hematology, Maternity and Children Hospital, Mecca, Saudi Arabia., Alzahrani A; Department of Laboratory and Blood Bank at Maternity and Children Hospital, Mecca, Saudi Arabia., Aljohani F; Department of Pediatric Clinics, Maternity and Children Hospital, King Salman Medical City, Madinah, Saudi Arabia., Melibary EM; Department of Medical Genetics, College of Medicine, Umm Al-Qura University, P.O. Box 57543, Mecca, 21955, Saudi Arabia., Kensara OA; Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Umm Al-Qura University, Jeddah, Saudi Arabia.; Department of Biochemistry, Batterjee Medical College, Jeddah, Saudi Arabia. |
| المصدر: | Human genomics [Hum Genomics] 2022 Jul 19; Vol. 16 (1), pp. 22. Date of Electronic Publication: 2022 Jul 19. |
| نوع المنشور: | Journal Article; Review; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101202210 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-7364 (Electronic) Linking ISSN: 14739542 NLM ISO Abbreviation: Hum Genomics Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2012- : London : BioMed Central Original Publication: London : Henry Stewart Publications, c2003- |
| مواضيع طبية MeSH: | Phenylalanine Hydroxylase*/genetics , Phenylalanine Hydroxylase*/metabolism , Phenylalanine Hydroxylase*/therapeutic use , Phenylketonurias*/genetics , Phenylketonurias*/therapy, Humans ; Phenylalanine/metabolism ; Phenylalanine/therapeutic use |
| مستخلص: | This review discusses the epidemiology, pathophysiology, genetic etiology, and management of phenylketonuria (PKU). PKU, an autosomal recessive disease, is an inborn error of phenylalanine (Phe) metabolism caused by pathogenic variants in the phenylalanine hydroxylase (PAH) gene. The prevalence of PKU varies widely among ethnicities and geographic regions, affecting approximately 1 in 24,000 individuals worldwide. Deficiency in the PAH enzyme or, in rare cases, the cofactor tetrahydrobiopterin results in high blood Phe concentrations, causing brain dysfunction. Untreated PKU, also known as PAH deficiency, results in severe and irreversible intellectual disability, epilepsy, behavioral disorders, and clinical features such as acquired microcephaly, seizures, psychological signs, and generalized hypopigmentation of skin (including hair and eyes). Severe phenotypes are classic PKU, and less severe forms of PAH deficiency are moderate PKU, mild PKU, mild hyperphenylalaninaemia (HPA), or benign HPA. Early diagnosis and intervention must start shortly after birth to prevent major cognitive and neurological effects. Dietary treatment, including natural protein restriction and Phe-free supplements, must be used to maintain blood Phe concentrations of 120-360 μmol/L throughout the life span. Additional treatments include the casein glycomacropeptide (GMP), which contains very limited aromatic amino acids and may improve immunological function, and large neutral amino acid (LNAA) supplementation to prevent plasma Phe transport into the brain. The synthetic BH4 analog, sapropterin hydrochloride (i.e., Kuvan®, BioMarin), is another potential treatment that activates residual PAH, thus decreasing Phe concentrations in the blood of PKU patients. Moreover, daily subcutaneous injection of pegylated Phe ammonia-lyase (i.e., pegvaliase; PALYNZIQ®, BioMarin) has promised gene therapy in recent clinical trials, and mRNA approaches are also being studied. (© 2022. The Author(s).) |
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| فهرسة مساهمة: | Keywords: Epidemiology; Genetic etiology; PKU management; Pathophysiology; Phenylalanine hydroxylase; Phenylketonuria; Tetrahydrobiopterin |
| المشرفين على المادة: | 47E5O17Y3R (Phenylalanine) EC 1.14.16.1 (Phenylalanine Hydroxylase) |
| تواريخ الأحداث: | Date Created: 20220719 Date Completed: 20220721 Latest Revision: 20220910 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9295449 |
| DOI: | 10.1186/s40246-022-00398-9 |
| PMID: | 35854334 |
| قاعدة البيانات: | MEDLINE |
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