Phenylketonuria: Dietary and therapeutic challenges

Giovannini, Marcello; Verduci, Elvira; Salvatici, E.; Fiori, Laura M.; Riva, Enrica

doi:10.1007/s10545-007-0552-8

Cited by 70 publications

(46 citation statements)

References 61 publications

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“…Still others may assume that their protein-restricted diet is normal as they are accustomed to protein restriction since early childhood. As a consequence, deficiencies of trace elements, vitamins, minerals, and amino acids may result because diet is not supplemented with AAM (Giovannini et al 2007;Feillet and Agostoni 2010;MacDonald et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Dietary Habits and Metabolic Control in Adolescents and Young Adults with Phenylketonuria: Self-Imposed Protein Restriction May Be Harmful

et al. 2013

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Background: In untreated patients, phenylketonuria (PKU) results in severe encephalopathy with mental retardation. A protein-restricted diet is recommended which can be relaxed in adolescence/adulthood.Methods: We contacted all 72 adult/adolescent PKU patients who had been treated in our center during early childhood. Some still regularly attended our outpatient clinics, while others were lost for follow-up, giving 51 patients in our study. We asked all patients to complete a dietary protocol as well as a questionnaire on quality of life. Blood and urine were analyzed and body impedance plethysmography and cerebral MRI were performed.Results: 42 % of the patients followed protein restriction supplemented with amino acid mixtures (AAM), others had a vegan diet with (8 %) or without (14 %) AAM; 36 % said they were eating normally and did not need any AAM. However, based on dietary protocols and blood urea levels, protein intake was restricted in this patient group. None of the patients examined had serious nutritional deficits. Phenylalanine levels were higher in patients not taking AAM. MRI of the brain was not different from those following protein restriction and taking AAM. The lesions score and mood correlated best with the cumulative phenylalanine values during the first 10 years of life.Conclusion: In summary, 50 % of adult/adolescent patients from our center did not take AAM at the start of our survey although they unknowingly followed selfimposed protein restriction. They had no overt nutritional deficits; however, long-term brain function may be compromised. Our study emphasizes the need for specialized metabolic care in PKU during adulthood.

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Section: Introductionmentioning

confidence: 99%

Dietary Habits and Metabolic Control in Adolescents and Young Adults with Phenylketonuria: Self-Imposed Protein Restriction May Be Harmful

et al. 2013

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“…In general, the usual treatment goal is a blood Phe level of 120 to 360 mmol/L (National Institutes of Health 2001; Poustie and Wildgoose 2010). In addition to the lowPhe diet, patients replace nutrients that are absent in their restricted diet with Phe-free medical foods (Giovannini et al 2007). With adherence to a Phe-restricted diet, poor outcomes can be mitigated.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of BH4 (Sapropterin) for the Adjuvant Treatment of Phenylketonuria

Lindegren

Krishnaswami²,

Reimschisel

et al. 2012

JIMD Reports

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Context: Dietary management is the mainstay of effective treatment in PKU, but dietary restriction is difficult and additional treatment options are needed.Objective: To systematically review evidence regarding sapropterin (BH4) use as an adjunct to dietary restriction in individuals with PKU.Data Sources: Five databases including MEDLINE up to August 2011.Study Selection: Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria.Data Extraction: Two reviewers independently extracted data regarding participant and intervention characteristics and outcomes and assigned overall quality and strength of evidence ratings based on predetermined criteria.Results: BH4 research includes two randomized controlled trials (RCTs) and three uncontrolled open-label trials. Phenylalanine (Phe) levels were reduced by at least 30 % in up to half of treated participants (32-50 %). In one RCT comparing placebo on likelihood of a 30 % reduction in Phe, 9 % of those on placebo achieved this effect, compared with 44 % of the treated group after 6 weeks. Phe tolerance and variability were improved in treated participants in studies assessing those outcomes. No comparative studies assessed long-term outcomes including cognitive effects, nutritional status, or quality of life.Conclusions: Adjuvant pharmacologic therapy has the potential to support individuals in achieving optimal Phe levels. BH4 has been shown to reduce Phe levels in some individuals, with significantly greater reductions seen in treated versus placebo groups. The strength of the evidence is moderate for short-term effects on reducing Phe in a subset of initially BH4-responsive individuals, moderate for a lack of significant harms, low for longerterm effects on cognition, and insufficient for all other outcomes.

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“…Treatment must be neonatally established in order to prevent neurological damage. Other clinical manifestations are "mousy" odour, light skin pigmentation, peculiar sitting posture, eczema, epilepsy, etc (Scriver & Kaufman 2001;Giovannini et al, 2007). PAH deficiency is highly heterogeneous showing an enormous phenotypic variability.…”

Section: Introductionmentioning

confidence: 99%

PKU in Minas Gerais State, Brazil: Mutation Analysis

Santos

Castro-Magalhães

Fonseca

et al. 2008

Annals of Human Genetics

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SummaryThis work was undertaken in order to ascertain the PKU mutational spectrum in Minas Gerais, Brazil, the relative frequency of the mutations in the State and the origin of these mutations by haplotype determination. Minas Gerais is a trihybrid population formed by miscegenation from Europeans, Africans and Amerindians. All 13 exons of the PAH gene from 78 PKU patients were analyzed, including splicing sites and the promoter region. We identified 30 different mutations and 98% of the PAH alleles were established. A new mutation (Q267X) was identified as well. The most common mutations found were V388M (21.2), R261Q (16.0%), IVS10-11G>A (15.3%), I65T (5.8%), IVS2+5G>C (5.8%), R252W (5.1%), IVS2+5G>A (4.5%), P281L (3.8%) and L348V (3.2%). These nine mutations correspond to 80% of the PKU alleles in the state. Haplotypes were determined to characterize the origin of the PAH alleles. The majority of the mutations found, with respective haplotypes, are frequent in the Iberian Peninsula. However, there were some mutations that are rare in Europe and four previously unreported mutation-haplotype associations. I65T and Q267X were found in association with haplotype 38 and may be African in origin or the result of miscegenation in the Brazilian population.

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Phenylketonuria: Dietary and therapeutic challenges

Cited by 70 publications

References 61 publications

Dietary Habits and Metabolic Control in Adolescents and Young Adults with Phenylketonuria: Self-Imposed Protein Restriction May Be Harmful

Dietary Habits and Metabolic Control in Adolescents and Young Adults with Phenylketonuria: Self-Imposed Protein Restriction May Be Harmful

A Systematic Review of BH4 (Sapropterin) for the Adjuvant Treatment of Phenylketonuria

PKU in Minas Gerais State, Brazil: Mutation Analysis

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