Information processing in patients with early and continuously-treated phenylketonuria

Stemerdink, B.A.; Meere, van der Jacob; Molen, Maurits W. van der; Kalverboer, Alex; Hendrikx, M. M. T.; Huisman, J.; Schot, L.W.A. van der; Slijper, F. M. E.; Spronsen, van FrancJan; Ph, Verkerk

doi:10.1007/bf02276719

Cited by 41 publications

(38 citation statements)

References 24 publications

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“…69 Notably, although studies have not been uniform, deficits in executive function in individuals with PAH deficiency are consistent enough to warrant special attention. 27,[72][73][74][75][76][77][78][79][80][81][82][83] …”

Section: Acmg Practice Guidelines Neurocognitive and Psychological Oumentioning

confidence: 99%

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

544

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: Acmg Practice Guidelines Neurocognitive and Psychological Oumentioning

confidence: 99%

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

544

443

View full text Add to dashboard Cite

show abstract

“…10 Early and continuous dietary therapy prevents the more severe neurological and intellectual dysfunction associated with classic PKU, but more subtle deficits in intelligence, academic achievement, and executive functioning can occur even in individuals with PKU who are treated early. [11][12][13] Despite functioning within the average range on tests of intelligence, children and adults with PKU have a lower mean intelligence quotient (IQ) than the general population. 12,14,15 Deficits affecting language skills, visual-spatial abilities, processing speed, verbal comprehension, and perceptual reasoning skills have also been reported.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13] Despite functioning within the average range on tests of intelligence, children and adults with PKU have a lower mean intelligence quotient (IQ) than the general population. 12,14,15 Deficits affecting language skills, visual-spatial abilities, processing speed, verbal comprehension, and perceptual reasoning skills have also been reported. 13,[16][17][18][19][20] A meta-analysis of Phe levels and IQ in 40 studies confirmed a significant negative correlation between blood Phe levels and IQ in individuals with PKU who were treated early.…”

Section: Introductionmentioning

confidence: 99%

Long-term developmental progression in infants and young children taking sapropterin for phenylketonuria: a two-year analysis of safety and efficacy

Longo

Siriwardena

Feigenbaum

et al. 2015

Genetics in Medicine

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“…This includes even those that are not typically regarded as protein providers, such as fruits and vegetables. It is therefore common practice in Germany and many other, but not all, countries to calculate phe intake from all foods to achieve tolerable phe plasma concentrations (Burgard et al, 1999;Stemerdink et al, 2000;Anon, 2001).…”

Section: Introductionmentioning

confidence: 99%

Unrestricted consumption of fruits and vegetables in phenylketonuria: no major impact on metabolic control

Rohde¹,

Mütze²,

Weigel³

et al. 2012

Eur J Clin Nutr

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Background/Objectives: The treatment of phenylketonuria (PKU) requires consistent restriction of protein intake from natural sources. Therefore, protein from all foods has to be accounted for, even the small amounts in fruits and vegetables. We studied whether free consumption of fruits and vegetables containing less than 75 mg phenylalanine (phe) per 100 g affects metabolic control in children with PKU. Subjects/Methods: Fourteen children (2-10 years) were included in a cross-over study, with a two-week period of conventional treatment (accounting for protein from fruits and vegetables) and a two-week period with free fruit and vegetable consumption. The instruction to follow liberal fruit and vegetable consumption in the first or second study period was randomized. Detailed daily dietary records were obtained throughout the study. Phe and nutrient content was calculated. Dried-blood phe concentration was monitored daily. Results: Although total phe intake increased by an average of 58 mg per day (P ¼ 0.037) during the 2 weeks of free fruit and vegetable consumption, dried-blood phe concentrations were unchanged. Total intake of fruits and vegetables did not increase, but patients instead used the higher phe tolerance to consume more of other foods, which were calculated and accounted for. Conclusion: Free consumption of fruits and vegetables does not impair metabolic control in PKU patients over a 2-week period.

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Information processing in patients with early and continuously-treated phenylketonuria

Cited by 41 publications

References 24 publications

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Long-term developmental progression in infants and young children taking sapropterin for phenylketonuria: a two-year analysis of safety and efficacy

Unrestricted consumption of fruits and vegetables in phenylketonuria: no major impact on metabolic control

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