Significance of genotype in tetrahydrobiopterin‐responsive phenylketonuria

Trefz, Friedrich K.; Scheible, D.; Götz, H; Frauendienst-Egger, G.

doi:10.1007/s10545-008-0940-8

Cited by 58 publications

(60 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18,19 Mutation analysis should be obtained for all infants with elevated PHE to provide information that may affect the extent of dietary PHE restriction and the likelihood of response to cofactor (BH 4 ; sapropterin) supplementation, with submission of results to the PAH databases. [20][21][22][23] …”

Section: Genotypingmentioning

confidence: 99%

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

528

443

View full text Add to dashboard Cite

Phenylalanine hydroxylase (PAH) deficiency, traditionally called phenylketonuria (PKU) due to characteristic phenylketones accumulating in the urine of affected individuals, has a significant place in history as the first inborn error of metabolism identified through population-based screening, initiating a new era in the diagnosis and treatment of genetic disorders. PKU was first described in 1934 by the Norwegian physician Asbjörn Fölling, but it was not until the mid-1950s that a patient with PAH deficiency was treated with a low phenylalanine (PHE) diet. Although this first patient already had irreversible Phenylalanine hydroxylase deficiency, traditionally known as phenylketonuria, results in the accumulation of phenylalanine in the blood of affected individuals and was the first inborn error of metabolism to be identified through population screening. Early identification and treatment prevent the most dramatic clinical sequelae of the disorder, but new neurodevelopmental and psychological problems have emerged in individuals treated from birth. The additional unanticipated recognition of a toxic effect of elevated maternal phenylalanine on fetal development has added to a general call in the field for treatment for life. Two major conferences sponsored by the National Institutes of Health held >10 years apart reviewed the state of knowledge in the field of phenylalanine hydroxylase deficiency, but there are no generally accepted recommendations for therapy. The purpose of this guideline is to review the strength of the medical literature relative to the treatment of phenylalanine hydroxylase deficiency and to develop recommendations for diagnosis and therapy of this disorder. Evidence review from the original National Institutes of Health consensus conference and a recent update by the Agency for Healthcare Research and Quality was used to address key questions in the diagnosis and treatment of phenylalanine hydroxylase deficiency by a working group established by the American College of Medical Genetics and Genomics. The group met by phone and in person over the course of a year to review these reports, develop recommendations, and identify key gaps in our knowledge of this disorder.Above all, treatment of phenylalanine hydroxylase deficiency must be life long, with a goal of maintaining blood phenylalanine in the range of 120-360 µmol/l. Treatment has predominantly been dietary manipulation, and use of low protein and phenylalanine medical foods is likely to remain a major component of therapy for the immediate future. Pharmacotherapy for phenylalanine hydroxylase deficiency is in early stages with one approved medication (sapropterin, a derivative of the natural cofactor of phenylalanine hydroxylase) and others under development. Eventually, treatment of phenylalanine hydroxylase deficiency will be individualized with multiple medications and alternative medical foods available to tailor therapy. The primary goal of therapy should be to lower blood phenylalanine, and any interventions, including medica...

show abstract

Section: Genotypingmentioning

confidence: 99%

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

528

443

View full text Add to dashboard Cite

show abstract

“…13 Genotyping, by itself, can not be used as a definitive diagnostic test for cofactor sensibility, and it should be combined with a BH4-loading test. 14 The high sensitivity of molecular diagnostics enables detection of heterozygotes in familial risk constellations.…”

Section: Diagnostic Settingmentioning

confidence: 99%

Clinical utility gene card for: Phenylketonuria

Zschocke

Haverkamp²,

Møller

2011

Eur J Hum Genet

View full text Add to dashboard Cite

“…The p.L48S mutation as well as seven others (p.R158Q, p.R261Q, p.I306V, p.E390G, p.A403V, p.R413P, and p.Y414C) were characterized as BH4-responsive ones in previous European studies (Zurfl€ uh et al 2008;Trefz et al 2009a;Karacic et al 2009). Accordingly, the sum of relative frequencies of BH4-responsive mutations for Serbian population is 52.6%.…”

Section: Bh4 Responsivenessmentioning

confidence: 94%

“…Later on, it became clear that BH4-responsive genotype has a greater BH4-responsive predictive value (Trefz et al 2009a;Karacic et al 2009). In order to make the most accurate estimation of the potential of BH4-supplementation therapy, we classified Serbian PAH genotypes into BH4 responsive, probably BH4 responsive, and non-BH4 responsive (Table 3) (Sterl et al 2012).…”

Section: Bh4 Responsiveness In Serbiamentioning

confidence: 99%