Phenylketonuria is a rare inherited disorder. It is the inability of the body to metabolize phenyalanine (an Amino Acid), which causes brain damage and nerve damage if left untreated. It can be detected early in new born babies by screening them as soon as they are born and this babies, adults and children are put on a strict low-diet proteins foods. PKU is caused by the absence of phenylalanine hydroxylase enzyme activity which is due to a mutation in a gene on chromosome 12.
A sweetener called "ASPARTAME" can also be poisonous for people with phenylketonuria. PKU is a rare disorder but is very important to identify. With early detection and consistent treatment, its damaging effects can be minimized and patients can have a normal life span with normal mental development. The best known treatment is a strict phenyalanine-restricted diet supplement prepared using a medical formula which contains amino acids and other nutrients. PKU is not a result of the environment or effects of the parents actions, it is inherited by the child if both parents have at least one mutated allele for the phenyalanine hydroxylase enzyme gene (the child needs to inherit 2 mutated gene in order to test positive for PKU). Most parents who are carriers of this mutation are not aware because they have no medical condition that determines its existence in them. If both parents are carriers, there is a 25% chance of birthing a child with the disorder, 50% chance of birthing a carrier and a 25% of birthing a child who is neither a carrier nor would he/she have the disorder.
To screen for PKU; it is done by bacterial inhibition assay, immunoassays using fluorometric or photo-metric detection or by amino acid detection using tandem mass spectrometry (MS/MS). The measurement done using MS/MS determines the concentration of Phe and the ratio of Phenylalanine (Phe) to Tyrosine (Tyr), the ratio is always high in PKU. It is always impossible to test for PKU at the birth of a baby because the baby would have a normal birth due to the fact that the mother's body breaks down phenylalanine during pregnancy thus there are no detectable damages done to the baby.
A routine newborn screening test is performed 2-7 days after the birth of the baby before a phenylalanine restricted diet has been introduced and blood samples are taken by "neonatal heel prick". The phenylalanine levels in the blood will increase over time, toxic levels of phenylalanine and an insufficient levels of tyrosine in the infant interferes with infant envelopment which causes permanent effects.
Clinical presentations of the disease include;
- Seizures
- Hypo-pigmentation (i.e, excessive fair hair and skin)
- musty odor to sweat and urine (this is due to phenylacetate, which is a carboxylic acid produced by the oxidation of phenylketone). It is usually advisable to have a repeat test at approximately two weeks of age to verify the initial test.
- Hyperactivity
- EEG abnormalities
- Eczema (skin rash)
- Microcephaly
- Severe learning disabilities.
When children are left untreated, they fail to attain early developmental milestones and they develop microcephaly and exhibit progressive impairment of cerebral function. The damage done to the brain during the first months of life is irreversible. PKU is not a curable disorder but can be managed by controlling the level of Phe in the diet or through a combination of diet and medication.
An allowable limit of 2mg/dL to 6mg/dL is recommended in the first 10 years of the child in order for the brain to develop normally.
A PKU diet requires the restriction of foods high in Phenylalanine such as soybeans, seal meat, egg white, shrimps, chicken breast, spirulina, watercress, fish, nuts, crayfish, tuna, turkey, lobster, elk meat, legumes, low-fat cottage cheese e.t.c.
A food diary is used to keep track of the amount of Phe consumed with each meal, snack or drink. A lower-protein "medical food" is usually substituted for grain-based foods, bread and pasta. Fruits and vegetables are very low in Phe, therefore can be eaten in large quantities. An infant can be breastfed but in smaller quantity in order for the infant to get the required nutrients it needs and any other missing nutrient is replaced through supplementation. A supplementary protein substitute formulas are prescribed for classical PKU patients starting from infancy which provides the amino acids and other necessary nutrients that would other-wise be lacking in a low-phenyalanine diet. Tyrosine which is required for the brain function is always supplemented. Tyrosine is derived from the breakdown of Phenyalanine. Women with PKU (although not at risk of additional complications during pregnancy) are advised to maintain low Phe levels before and during pregnancy for health benefits of their children. The intrauterine environment could have very high levels of phenylalanine which may cross the placenta to the developing fetus and the fetus may develop congenital heart disease, growth retardation, microcephaly and intellectual disability. The mother's daily Phe intake could double or triple by the end of her pregnancy. When the maternal blood Phe levels fall below 2mg/dL, her anecdotal reports indicate that the mothers may suffer adverse effects like headaches, nausea, hair loss, and general malaise.
When low levels of Phe are maintained for the duration of pregnancy, there are no elevated levels of risk of birth defects when compared to a baby of a non-PKU mother.
