Adults with late diagnosed PKU and severe challenging behaviour: a randomised placebo-controlled trial of a phenylalanine-restricted diet

Lee, Philip J.; Amos, Allayne; Robertson, Lesley; Fitzgerald, Brian; Hoskin, Rosemary; Lilburn, Maggie; Weetch, Eleanor; Murphy, Glynis H.

doi:10.1136/jnnp.2008.151175

Cited by 45 publications

(33 citation statements)

References 21 publications

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“…For these adults, the optimal serum Phe level was individually chosen and can be seen as a compromise between the effects on patients' emotional and behavioural functions and their ability to adhere to and manage the diet. The Phe levels in this study are comparable to the levels reported in other studies for late-diagnosed patients with PKU (Lee et al 2009;Trefz et al 2011) and to the levels reported to have positive effects on early-treated adult patients' mood and attention (Ten Hoedt et al 2011).…”

Section: Discussionsupporting

confidence: 88%

“…Patients born prior to this date were usually diagnosed late and developed various degrees of brain damage. It has been documented that dietary treatment started on clinical indications, during childhood or in adult years, can alleviate neurological and behavioural symptoms and signs also in late diagnosed patients (Yannicelli and Ryan 1995;Baumeister and Baumeister 1998;Fitzgerald et al 2000;Lee et al 2009). In Norway, late diagnosed adults with PKU are offered dietary treatment on a permanent basis if they experience positive effects on neurological and behavioural symptoms during a trial period, usually lasting 3 to 6 months.…”

Section: Introductionmentioning

confidence: 99%

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Nutritional Consequences of Adhering to a Low Phenylalanine Diet for Late-Treated Adults with PKU

et al. 2012

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Background: The main treatment for phenylketonuria (PKU) is a low phenylalanine (Phe) diet, phenylalaninefree protein substitute and low-protein special foods. This study describes dietary composition and nutritional status in late-diagnosed adult patients adhering to a PKU diet.Methods: Nineteen patients, followed at Oslo University Hospital in Norway, participated; median age was 48 years (range 26-66). Subjects were mild to severely mentally retarded. Food intake, clinical data and blood analyses relevant for nutritional status were assessed.Results: Median energy intake was 2,091 kcal/day (range 1,537-3,277 kcal/day). Carbohydrates constituted 59% (range 53-70%) of the total energy, including 15% from added sugar; 26% was from fat. The total protein intake was 1.02 g/kg/day (range 0.32-1.36 g/kg/day), including 0.74 g/kg/day (range 0.13-1.07 g/kg/day) from protein substitutes. Median dietary Phe intake was 746 mg/day (range 370-1,370 mg/day). Median serum Phe was 542 mmol/L (range 146-1,310 mg/day). Fortified protein substitutes supplied the main source of micronutrients. Iron intake was 39.5 mg/day (range 24.6-57 mg/day), exceeding the upper safe intake level. Intake of folate and folic acid, calculated as dietary folate equivalents, was 1,370 mg/day (range 347-1744 mg/day), and resulted in high blood folate concentrations. Median intake of vitamin B 12 was 7.0 mg/day (range 0.9-15.1 mg/day).Conclusions: The diet supplied adequate protein and energy. Fortification of the protein substitutes resulted in excess intake of micronutrients. The protein substitutes may require adjustment to meet nutritional recommendations for adults with PKU.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Nutritional Consequences of Adhering to a Low Phenylalanine Diet for Late-Treated Adults with PKU

et al. 2012

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“…That said, an individual's specific PAH genotype is still the major determinant of metabolic phenotype. 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%

“…PAH deficiency most accurately describes the spectrum of clinical phenotypes ranging from PKU to hyperphenylalaninemia and thus will be used throughout this guideline. Tetrahydrobiopterin (BH 4 ) is a necessary cofactor for PAH activity, and rare genetic defects in the pathway of BH 4 synthesis or recycling can lead to secondary PAH deficiency and elevated blood PHE levels. Treatment of these defects, which present differently than PAH deficiency and have largely different therapy, is not considered further in this guideline.…”

mentioning

confidence: 99%

“…Even severely intellectually disabled adults with late-diagnosed PAH deficiency show improvements in challenging behavior with lowering of blood PHE levels. 4 Pregnancy presents a particular problem in women with PAH deficiency; as high levels of PHE are toxic to the brain of the developing fetus and, along with other teratogenic effects, result in a defined maternal PKU (MPKU) syndrome.…”

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confidence: 99%

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Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

499

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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Transition to adult care for children with chronic neurological disorders

Camfield

2011

Annals of Neurology

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Chronic neurological disorders in children have significant effects on adult medical and social function. Transition and then formal transfer of care from pediatric to adult services is a complex process, although there are virtually no objective data to inform physicians about the most effective approach. Some neurological disorders that start in children are a danger to society if poorly treated in adulthood, some disorders that were previously lethal in childhood now permit survival well into adulthood, and others are static in childhood but progressive in adulthood. Some disorders remit or are cured in childhood but continue to have serious comorbidity in adulthood, whereas others are similar and persistent in children and adults. Maturity, provision of information, and cognitive problems are confounders. We discuss several models of transition/transfer but prefer a joint pediatric/adult transition clinic. We make a series of suggestions about how to improve the transition/transfer process with the hope of better medical and social adult outcome for children with neurological disorders.

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Adults with late diagnosed PKU and severe challenging behaviour: a randomised placebo-controlled trial of a phenylalanine-restricted diet

Cited by 45 publications

References 21 publications

Nutritional Consequences of Adhering to a Low Phenylalanine Diet for Late-Treated Adults with PKU

Nutritional Consequences of Adhering to a Low Phenylalanine Diet for Late-Treated Adults with PKU

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Transition to adult care for children with chronic neurological disorders

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