title: Four Years of Diagnostic Challenges with Tetrahydrobiopterin Deficiencies in Iranian Patients.
abstract: Hyperphenylalaninemia (HPA) is a condition caused by tetrahydrobiopterin (BH4) and phenylalanine hydroxylase (PAH) deficiencies. It is essential that differential diagnosis be conducted to distinguish these two causes of HPA, because BH4deficiency is a more severe disease involving progressive neurologic deterioration. Based on the biological findings, HPA is defined as a plasma phenylalanine level of >2.0 mg/dl (>120 μmol/l). The National Biochemistry Reference Laboratory at the Pasteur Institute of Iran initiated BH4deficiency screening tests for the first time during the implementation of a nationwide phenylketonuria (PKU) screening program. Measurement of blood phenylalanine and urinary neopterin and biopterin was conducted by high-performance liquid chromatography in 617 patients with HPA. Dihydropteridine reductase (DHPR) activity was measured in all patients by kinetic spectrophotometry. Differential diagnosis was conducted for PKU, transient HPA, and BH4deficiencies.Our results indicated that out of 76 cases involving BH4deficiencies, 37 had 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency, 35 had DHPR deficiency, 1 case had pterin-4a-carbinolamine dehydratase (PCD) deficiency, and 3 cases had GTP cyclohydrolase I (GTPCH) deficiency. In this study, 1 novel deletion mutation and 18 novel missense mutations were reported in addition to mutations that had previously been identified and registered in BIOMDB. At present, the screening program for PKU in Iran includes tests that detect different forms of BH4deficiency presenting with HPA. Newborns that are BH4-deficient benefit from the availability of the tests because they can receive necessary care before being clinically affected.
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Pasteur Street, No. 69, 1316943551, Tehran, Iran. sh-khatami@pasteur.ac.ir.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Khatami
authors.affiliation: Department of Biochemistry, Pasteur Institute of Iran, Pasteur Street, No. 69, 1316943551, Tehran, Iran. SRD@pasteur.ac.ir.
authors.forename: Soghra Rouhi
authors.initials: SR
authors.lastname: Dehnabeh
authors.affiliation: Genetic Laboratory of Dr Zeinali, Tehran, Iran.|Department of Medical Molecular, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Sirous
authors.initials: S
authors.lastname: Zeinali
authors.affiliation: Division of Clinical Chemistry and Biochemistry, Laboratory of Molecular Genetic Investigation, University Children's Hospital Zürich, Zürich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Thöny
authors.affiliation: Mofid Children's Hospital, Shaid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Alaei
authors.affiliation: Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Shadab
authors.initials: S
authors.lastname: Salehpour
authors.affiliation: Growth and Development Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Aria
authors.initials: A
authors.lastname: Setoodeh
authors.affiliation: Department of Pediatrics Endocrinology and Metabolism, Ali Asghar Children's Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Rohani
authors.affiliation: Genetics Office, CDC, Ministry of Health of Iran, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Hajivalizadeh
authors.affiliation: Genetics Office, CDC, Ministry of Health of Iran, Tehran, Iran.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Samavat
keywords: BH4 deficiencies; Hyperphenylalaninemia; Phenylketonuria