Tetrahydrobiopterin deficiencies: Lesson from clinical experience.

Autor: Bozaci AE; Department of Pediatrics, Division of Pediatric Metabolism Ege University Faculty of Medicine Izmir Turkey., Er E; Tepecik Research and Training Hospital, Department of Genetics Izmir Turkey., Yazici H; Department of Pediatrics, Division of Pediatric Metabolism Ege University Faculty of Medicine Izmir Turkey., Canda E; Department of Pediatrics, Division of Pediatric Metabolism Ege University Faculty of Medicine Izmir Turkey., Kalkan Uçar S; Department of Pediatrics, Division of Pediatric Metabolism Ege University Faculty of Medicine Izmir Turkey., Güvenc Saka M; Tepecik Research and Training Hospital, Department of Genetics Izmir Turkey., Eraslan C; Department of Radiology Ege University Faculty of Medicine Izmir Turkey., Onay H; Department of Medical Genetics Ege University Faculty of Medicine Izmir Turkey., Habif S; Department of Medical Biochemistry Ege University Faculty of Medicine Izmir Turkey., Thöny B; Division of Metabolism University Children's Hospital Zurich and Children's Research Center Zurich Switzerland., Coker M; Department of Pediatrics, Division of Pediatric Metabolism Ege University Faculty of Medicine Izmir Turkey.
Jazyk: angličtina
Zdroj: JIMD reports [JIMD Rep] 2021 Feb 01; Vol. 59 (1), pp. 42-51. Date of Electronic Publication: 2021 Feb 01 (Print Publication: 2021).
DOI: 10.1002/jmd2.12199
Abstrakt: Objectives: The present study describes clinical, biochemical, molecular genetic data, current treatment strategies and follow-up in nine patients with tetrahydrobiopterin (BH4) deficiency due to various inherited genetic defects.
Methods: We analyzed clinical, biochemical, and molecular data of nine patients with suspected BH4 deficiency. All patients were diagnosed at Ege University Faculty of Medicine in Izmir, Turkey and comprised data collected from 2006 to 2019. The diagnostic laboratory examinations included blood phenylalanine and urinary or plasma pterins, dihydropteridine reductase (DHPR) enzyme activity measurement in dried blood spots, folic acid and monoamine neurotransmitter metabolites in cerebrospinal fluid, as well as DNA sequencing.
Results: Among the nine patients, we identified one with autosomal recessive GTP cyclohydrolase I (ar GTPCH) deficiency, two with 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, three with sepiapterin reductase (SR) deficiency, and three with DHPR deficiency. Similar to previous observations, the most common clinical symptoms are developmental delay, intellectual disability, and movement disorders. All patients received treatment with l-dopa and 5-hydroxytryptophan, while only the ar GTPCH, the PTPS, and one DHPR deficient patients were supplemented in addition with BH4. The recommended dose range varies among patients and depends on the type of disease. The consequences of BH4 deficiencies are quite variable; however, early diagnosis and treatment will improve outcomes.
Conclusions: As BH4 deficiencies are rare group of treatable neurometabolic disorders, it is essential to diagnose the underlying (genetic) defect in newborns with hyperphenylalaninemia. Irreversible brain damage and progressive neurological deterioration may occur in untreated or late diagnosed patients. Prognosis could be satisfying in the cases with early diagnose and treatment.
Competing Interests: Ayse Ergul Bozaci, Esra Er, Havva Yazici, Ebru Canda, Sema Ucar Kalkan, Merve Saka Guvenc, Cenk Eraslan, Huseyin Onay, Sara Habif, Beat Thony, Mahmut Coker declare that they have no conflict of interest.
(© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)
Databáze: MEDLINE
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