Complications
An increased incidence of ADHD, and of the use of stimulant medication, is seen in patients with PKU.[20] The occurrence of this complication may be a reflection of the degree of metabolic control in that it is associated with elevated mean blood phenylalanine (phe) levels. Older patients who were well controlled in childhood but later abandon therapy may also have attentional problems that are reversible in many cases by re-institution of treatment and lowering of the blood phe level.
Patients with PKU have an increased incidence of depression, anxiety, and phobias, and difficulties forming stable adult relationships.[21] These outcomes seem to be related to the degree of metabolic control; improvement in some psychiatric manifestations can be observed when metabolic control is restored.
An increased incidence of osteopenia and osteoporosis has been demonstrated in young adult patients with PKU.[22] It is not clear whether this is related to the disease itself or to the protein- and phe-restricted diet. Some patients have had fractures with minimal trauma.
Hyper-phenylalaninaemia in a pregnant woman with PKU is toxic to the developing fetus.[23] Women with phe levels >908 micromol/L (15 mg/dL) during pregnancy have a risk >85% of having an infant with microcephaly and intellectual disability. Congenital heart disease and growth retardation also occur with increased frequency. The risk of fetal abnormalities seems to be dose-related; women with lower elevations of blood phe are also at increased, albeit somewhat lower, risk. If the blood phe level is brought down <363 micromol/L (6 mg/dL) before conception and maintained in that range throughout pregnancy, a normal outcome can be anticipated in most cases.[24] Unfortunately, many women who have not maintained strict metabolic control find it difficult to return to dietary therapy for purposes of pregnancy.
Chronic elevations of blood phe in infancy and in early childhood, beyond a certain threshold, result in abnormal myelination, small brain size, seizures, and diminished IQ.
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