title: Molecular analysis of the AGXT gene in patients suspected with hyperoxaluria type 1 and three novel mutations from Turkey.
abstract: Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive disease, caused by the defect of AGXT gene encoding hepatic peroxisomal alanine glyoxylateaminotransferase (AGT). This enzyme is responsible for the conversion of glyoxylate to glycine. The diagnosis of PH1 should be suspected in infants and children with nephrocalcinosis or nephrolithiasis. Early diagnosis and treatment is crucial in preventing disease progression to end stage kidney disease (ESKD). In this study, AGXT gene sequence analyses were performed in 82 patients who were clinically suspected (hyperoxaluria and nephrolithiasis or nephrocalcinosis with or without renal impairment) to have PH1. Disease causing mutations have been found in fifteen patients from thirteen families (18%). Novel mutations have been found (c.458T>A (p.L153X), c.733_734delAA (p.Lys245Valfs*11), c.52 C>T (p.L18F)) in three of 13 families. There were 3-year lag time between initial symptoms and the time of PH1 is suspected; additionally, 5.5-year lag time between initial symptoms and definitive diagnosis. Consanguinity was detected in 77% of the patients with mutation. After genetic diagnosis, one patient received combined kidney and liver transplantation. AGXT gene sequencing is now the choice of diagnosis of PH1 due to its non-invasive nature compared to liver enzyme assay. Early diagnosis and accurate treatment in PH1 is important for better patient outcomes.
authors.affiliation: Department of Pediatric Nephrology, Gazi University Medical Faculty, Turkey. Electronic address: eisiyel@gazi.edu.tr.
authors.forename: Emel
authors.initials: E
authors.lastname: Isiyel
authors.affiliation: Department of Pediatric Nephrology, Gazi University Medical Faculty, Turkey.
authors.forename: Sevcan A Bakkaloglu
authors.initials: SA
authors.lastname: Ezgu
authors.affiliation: Department of Pediatric Nephrology, Istanbul University Cerrahpasa Medical Faculty, Turkey.
authors.forename: Salim
authors.initials: S
authors.lastname: Caliskan
authors.affiliation: Department of Pediatric Nephrology, Akdeniz University Medical Faculty, Turkey.
authors.forename: Sema
authors.initials: S
authors.lastname: Akman
authors.affiliation: Department of Pediatric Nephrology, Celal Bayar University Medical Faculty, Turkey.
authors.forename: Ipek
authors.initials: I
authors.lastname: Akil
authors.affiliation: Department of Pediatric Nephrology, Inonu University Medical Faculty, Turkey.
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Tabel
authors.affiliation: Department of Pediatric Nephrology, Sisli Etfal Training and Research Hospital, Turkey.
authors.forename: Nurver
authors.initials: N
authors.lastname: Akinci
authors.affiliation: Department of Pediatric Nephrology, Karadeniz Technical University Medical Faculty, Turkey.
authors.forename: Elif Bahat
authors.initials: EB
authors.lastname: Ozdogan
authors.affiliation: Department of Pediatric Nephrology, Konya Training and Research Hospital, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozel
authors.affiliation: Department of Pediatric Nephrology, Hacettepe University Medical Faculty, Turkey.
authors.forename: Fehime Kara
authors.initials: FK
authors.lastname: Eroglu
authors.affiliation: Department of Pediatric Metabolic Disorders and Pediatric Genetics, Gazi University Medical Faculty, Turkey.
authors.forename: Fatih S
authors.initials: FS
authors.lastname: Ezgu
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D042241:Early Diagnosis; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D007223:Infant; D008297:Male; D009154:Mutation; D000637:Transaminases / Q000235:genetics*; D055815:Young Adult
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase
keywords: Alanine glyoxylateaminotransferase (AGXT) gene mutation; Primary hyperoxaluria type 1