Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies

Blau, Nenad; Hennermann, Julia B.; Langenbeck, U.; Lichter‐Konecki, Uta

doi:10.1016/j.ymgme.2011.08.017

Cited by 199 publications

(173 citation statements)

References 49 publications

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“…15 Pterins must be measured in urine or blood. 16 As this will not detect all disorders of tetrahydrobiopterin metabolism, erythrocyte dihydropterin reductase should be measured on whole blood spotted on filter paper. A quantitative assay for urinary neopterin and biopterin can confirm results obtained from the filter paper samples.…”

Section: Diagnostic Testingmentioning

confidence: 99%

“…If testing is to be done in early infancy, it is recommended that blood PHE levels first be lowered to 480-600 µmol/l. 16 Sapropterin has been used under the age of 4 years in PAH deficiency and in patients with biopterin synthesis defects. 36,40 Sapropterin responsiveness is commonly determined by obtaining a baseline blood PHE level on the day the medication is initiated (baseline) and then starting the patient on a single daily dose of sapropterin at 20 mg/kg.…”

Section: Pharmacotherapymentioning

confidence: 99%

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Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

528

443

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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...

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Section: Diagnostic Testingmentioning

confidence: 99%

Section: Pharmacotherapymentioning

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

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“…Differential diagnosis between PAH-and BH4-deficient patients was performed according to the published diagnostic criteria (Blau et al 2011). …”

Section: Sample Criteriamentioning

confidence: 99%

Molecular Characterization of QDPR Gene in Iranian Families with BH4 Deficiency: Reporting Novel and Recurrent Mutations

et al. 2015

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Newborn screening for PKU has been in practice in Iran since 2007. Some hyperphenylalaninemia cases have tetrahydrobiopterin (BH4) biosynthesis deficiency/ disorder. Several genes including QDPR (encodes DHPR enzyme, the necessary cofactor for PAH activity) have been associated with the BH4. Mutations have been previously described in the QDPR gene. The incidence of BH4 deficiency is expected to be higher in Iran due to high rate of consanguineous marriages.We identified a total of 93 BH4-deficient families. A multiplex set of STR markers linked to 4 genes responsible for the BH4 deficiency (i.e., GCH1, PCBD1, PTS, and QDPR genes) was used to quickly determine which gene may be responsible to cause the disease. Mutation analysis of QDPR gene revealed some known and novel mutations. Our findings show that no common mutation predominates, and they are scattered in the gene in our population.

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“…Patients with PKU lack phenylalanine hydroxylase (PAH), an enzyme that metabolizes phenylalanine into tyrosine (NIH, 2001;Blau, 2011). Phenylalanine is a common amino acid found in most protein-rich foods, such as milk, eggs, meat, and nuts.…”

Section: Phenylketonuriamentioning

confidence: 99%

“…Without PAH, phenylalanine will accumulate and thus will be converted to phenylpyruvate, which can be detected in the urine (Blau, 2011). PKU, if left untreated, will lead to developmental delay, microcephaly, albinism, seizures, and mental retardation (Trefz, 2011).…”

Section: Phenylketonuriamentioning

confidence: 99%

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy

et al. 2014

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Introduction: Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). Methods: The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. Results: The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. Conclusions: There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue. Muscle Nerve 49: 822–828, 2014

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Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies

Cited by 199 publications

References 49 publications

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Molecular Characterization of QDPR Gene in Iranian Families with BH4 Deficiency: Reporting Novel and Recurrent Mutations

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy

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