Maternal phenylketonuria: low phenylalaninemia might increase the risk of intra uterine growth retardation

Teissier, R.; Nowak, Emmanuel; Assoun, M.; Mention, Karine; Cano, Aline; Fouilhoux, Alain; Feillet, François; Ogier, H.; Oger, Emmanuel; Parscau, L. De

doi:10.1007/s10545-012-9491-0

Cited by 48 publications

(35 citation statements)

References 27 publications

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“…56 The incidence of intrauterine growth retardation is not increased if PHE control is achieved by 10 weeks gestation; however it increases with later onset of PHE control. 57 Additional attention should be paid to women with PAH deficiency who have themselves had poor PHE control throughout their lives. Lower maternal IQ, <85, is associated with later achievement of gestational PHE control and poorer fetal outcomes, although when optimal PHE control is achieved in mothers irrespective of their IQ, the fetal outcomes are improved.…”

Section: Clinical Featuresmentioning

confidence: 99%

“…58 Although studies have shown that PHE levels as low as 100 µmol/l are safe during gestation, there are concerns that persistently low maternal PHE levels, especially during the second and third trimesters, may be associated with an increased risk of IUGR. 57 The adverse effects of elevated PHE on the developing fetus warrant increased attention and intervention during gestation, with emphasis on preconception control as optimal. Women who become pregnant without appropriate PHE control will need significant support to attain PHE levels within the…”

Section: Clinical Featuresmentioning

confidence: 99%

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Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

526

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: Clinical Featuresmentioning

confidence: 99%

Section: Clinical Featuresmentioning

confidence: 99%

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Vockley

Andersson

Antshel

et al. 2014

Genetics in Medicine

526

443

View full text Add to dashboard Cite

show abstract

“…With respect to the second issue, phenylalanine concentrations were both statistically and clinically significantly lower at T2 and T3 compared to T1, showing levels <30 mmol/L. This indeed is of clinical importance since too low phenylalanine concentrations in PKU are related to impaired growth and development (Rouse 1966;Smith et al 1990;Teissier et al 2012), and possibly also to physical and mental development in HT1 (de Laet et al 2011;van Vliet et al 2014). …”

Section: Day-to-day Variation Is Comparable For Phenylalanine and Tyrmentioning

confidence: 93%

What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

et al. 2017

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Background: Treatment of hereditary tyrosinemia type 1 with nitisinone and phenylalanine and tyrosine restricted diet has largely improved outcome, but the best blood sampling time for assessment of metabolic control is not known. Aim: To study diurnal and day-to-day variation of phenylalanine and tyrosine concentrations in tyrosinemia type 1 patients. Methods: Eighteen tyrosinemia type 1 patients aged >1 year (median age 7.9 years; range 1.6-20.7) were studied. Capillary blood samples were collected 4 times a day (T1: pre-breakfast, T2: pre-midday meal, T3: before evening meal, and T4: bedtime) for 3 days. Linear mixed-effect models were used to investigate diurnal and day-to-day variation of both phenylalanine and tyrosine. Results: The coefficients of variation of phenylalanine and tyrosine concentrations were the lowest on T1 (13.8% and 14.1%, respectively). Tyrosine concentrations did not significantly differ between the different time points, but phenylalanine concentrations were significantly lower at T2 and T3 compared to T1 (50.1 mmol/L, 29.8 mmol/L, and 37.3 mmol/L, respectively). Conclusion: Our results indicated that for prevention of too low phenylalanine and too high tyrosine concentrations, measurement of phenylalanine and tyrosine pre-midday meal would be best, since phenylalanine concentrations are the lowest on that time point. Our results also indicated that whilst blood tyrosine concentrations were stable over 24 h, phenylalanine fluctuated. Day-to-day variation was most stable after an overnight fast for both phenylalanine and tyrosine. Therefore, in tyrosinemia type 1 patients the most reliable time point for measuring phenylalanine and tyrosine concentrations to enable interpretation of metabolic control is pre-breakfast.

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“…This results in both high tyrosine and low phenylalanine concentrations (De Laet et al 2011;Daly et al 2012;Wilson et al 2000), with dietary treatment being primarily monitored based on tyrosine concentrations. In phenylketonuria, too strict dietary treatment, resulting in "low" phenylalanine concentrations, has shown to be related to impaired growth and development (Teissier et al 2012;Rouse 1966;Smith et al 1990;Pode-Shakked et al 2013). In tyrosinemia type II, high tyrosine concentrations are associated with mental retardation.…”

Section: Introductionmentioning

confidence: 99%

Infants with Tyrosinemia Type 1: Should phenylalanine be supplemented?

et al. 2014

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Tyrosinemia type 1 (HT1) is an inborn error of tyrosine catabolism caused by fumarylacetoacetase deficiency. Biochemically, this results in accumulation of toxic metabolites including succinylacetone. Clinically, HT1 is characterized by severe liver, kidney, and neurological problems. Treatment with NTBC and dietary restriction of tyrosine and phenylalanine have strongly improved outcome, but impaired neurocognitive development has been reported. Whether impaired neurocognitive outcome results from high blood tyrosine or low blood phenylalanine concentrations is currently unknown. In this report, two HT1 newborns, diagnosed by neonatal screening, are presented. The first patient showed low phenylalanine concentrations, growth retardation, neurological impairments, and skin problems, clearly improving after institution of phenylalanine supplementation (~30 mg/kg/ day) at age 6 months, while both blood phenylalanine and tyrosine concentrations increased. In the second patient, phenylalanine supplementation (~20 mg/kg/day) was initiated as soon as low phenylalanine concentrations were observed at age 19 days. On this regimen, blood phenylalanine concentrations increased, and hypophenylalaninemia was less frequently observed than in the first patient, whereas blood tyrosine concentrations tended to increase. Clinically, no growth, neurological, or skin problems have been observed. The combination of knowledge obtained from these cases suggests that hypophenylalaninemia rather than hypertyrosinemia during the first months of life may impair neurocognitive development in young HT1 infants. Phenylalanine supplementation should really be considered in HT1 patients with consistently low blood phenylalanine concentrations during the first months of life. However, the minimal phenylalanine concentrations acceptable and the optimal phenylalanine supplementation regimen require further investigation.

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Maternal phenylketonuria: low phenylalaninemia might increase the risk of intra uterine growth retardation

Cited by 48 publications

References 27 publications

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

Phenylalanine hydroxylase deficiency: diagnosis and management guideline

What Is the Best Blood Sampling Time for Metabolic Control of Phenylalanine and Tyrosine Concentrations in Tyrosinemia Type 1 Patients?

Infants with Tyrosinemia Type 1: Should phenylalanine be supplemented?

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