1. Tetrahydrobiopterin deficiencies: Lesson from clinical experience
- Author
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Mahmut Çoker, Ayse Ergul Bozaci, Havva Yazıcı, Merve Güvenc Saka, Sara Habif, Esra Er, Ebru Canda, Sema Kalkan Uçar, Hüseyin Onay, Beat Thöny, Cenk Eraslan, University of Zurich, Kalkan Uçar, Sema, and Thöny, Beat
- Subjects
Research Report ,demography ,Movement disorders ,phenylalanine ,Endocrinology, Diabetes and Metabolism ,clinical evaluation ,retrospective study ,adverse event ,tetrahydrobiopterin deficiencies ,monoamine ,biogenic amine ,pterin ,Medicine ,DNA sequencing ,microcephaly ,l-Dopa ,nuclear magnetic resonance imaging ,Sepiapterin reductase ,l‐Dopa ,dried blood spot testing ,BH4 ,clinical article ,anthropometry ,adult ,homovanillic acid ,autosomal recessive inheritance ,Tetrahydrobiopterin ,brain damage ,biopterin ,PKU ,laboratory test ,drug deficiency ,disease severity ,5 hydroxytryptophan ,motor dysfunction ,electroencephalography ,early diagnosis ,medicine.medical_specialty ,6 pyruvoyltetrahydropterin synthase ,phenotype ,Urinary system ,GTP cyclohydrolase I ,folinic acid ,sepiapterin reductase ,Brain damage ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,sapropterin ,Article ,cerebrospinal fluid ,folic acid ,Genetics ,biochemistry ,inheritance ,human ,levodopa ,amantadine ,intellectual impairment ,medicine.disease ,RC648-665 ,radiology ,2724 Internal Medicine ,molecular genetics ,prognosis ,swallowing ,Pediatrics ,Sanger sequencing ,genomic DNA ,oculogyric crisis ,apathy ,QH426-470 ,Hyperphenylalaninemia ,gene mutation ,biology ,dihydropteridine reductase ,neurologic disease ,enzyme activity ,2712 Endocrinology, Diabetes and Metabolism ,prolactin blood level ,female ,guanosine triphosphate cyclohydrolase I ,head circumference ,blood sampling ,medicine.symptom ,medicine.drug ,DHPR deficiency ,neurotransmitter ,health care personnel ,high performance liquid chromatography ,610 Medicine & health ,progeny ,1301 Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Diseases of the endocrine glands. Clinical endocrinology ,dysarthria ,male ,Internal Medicine ,follow up ,outcome assessment ,hyperphenylalaninemia ,muscle hypotonia ,business.industry ,hypersalivation ,Research Reports ,Dihydropteridine Reductase ,central nervous system ,dyskinesia ,neopterin ,10036 Medical Clinic ,electrochemiluminescence immunoassay ,biology.protein ,hypersomnia ,genetic disorder ,business - Abstract
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. © 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.
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- 2021