A practical approach to maternal phenylketonuria management

Abstract

More women with phenylketonuria are becoming pregnant and need appropriate management to avoid the effects of raised phenylalanine on the fetus: facial dysmorphism, microcephaly, growth retardation, developmental delay and congenital heart disease. Here we describe our experiences from a single centre gained over almost three decades. A series of six cases is presented to illustrate key points in management. Ideally, phenylalanine-restricted diet is started before conception in a planned fashion, but some women present pregnant and blood phenylalanine must be lowered rapidly. The aims of management are to maintain blood phenylalanine concentration in the target range (100-250 micromol/L) before and throughout the pregnancy, and to ensure adequate maternal nutrition and appropriate weight gain. Blood phenylalanine is monitored twice, three times a week, before and after conception respectively. Weight is monitored on a weekly basis and key micronutrients are monitored every 6-8 weeks in clinic. From the second trimester onwards, dietary phenylalanine intake has to be promptly increased, as phenylalanine tolerance increases rapidly. Postnatal management includes a neurological assessment of the infant at 4-8 weeks and an echocardiogram for infants conceived off diet. Subsequently, offspring are seen at 1 year, 4 years, 8 years and 14 years for neuropsychometric evaluations. Regular follow-up of the mother remains important whether on or off a phenylalanine-restricted diet.

Maternal phenylketonuria and hyperphenylalaninemia in pregnancy: pregnancy complications and neonatal sequelae in untreated and treated pregnancies

“…For this reason, an unambiguous policy to prevent maternal phenylketonuria syndrome is necessary. In this respect, women with a desire to become pregnant are advised to use a strict diet that starts before conception to prevent teratogenic effects in the fetus (6)(7)(8)(9)(10). During pregnancy, phenylalanine tolerance improves to some extent because of increased fetal phenylalanine-hydroxylase activity.…”

Maternales Phenylketonurie-Syndrom trotz intensiver Patientenberatung

“…The maternal PKU syndrome (or phenylalanine embryopathy) consists of facial dysmorphia, microcephaly, congenital heart defect (CHD), developmental delay and learning difficulties, and is caused by elevated maternal Phe levels during pregnancy, which exert teratogenic effects on the foetus [1][2][3][4].…”

“…Hence, closely monitored Pherestricted diet is required before conception and throughout pregnancy [1,2,4]. Maillot et al suggest continuing contraception until blood Phe concentrations in the recommended range are achieved for at least four weeks [3]. According to other investigators our target Phe levels before conception and throughout pregnancy are 120-360 mmol/l (2-6 mg/dl).…”

“…Even at rather low Phe levels the foetus may be protected from maternal Phe deficiency due to a positive concentration gradient across the human placenta [8]. A tight control of Phe metabolism is mandatory throughout pregnancy since Phe tolerance of the mother increases with the growing foetus in particular in the second and third trimester [3,8]. To prevent protein deficiency we prescribed a synthetically manufactured Phe-free amino acid mixture as the major protein source.…”

Study of determinants of health status and quality of life in pregnancy

“…Prenatalna identifikacija ovih faktora u rizičnim populacijama žena reproduktivnog doba koje planiraju trudnoću i antenatalni skrining fetalne genetike predstavljaju bitne odlike savremenog pristupa trudnoći, a posebno je važno što se nepoželjni efekti nekih genetskih faktora mogu uspešno prevazići [Maillot 2007]. …”