(PKU)phenylketonuria

Introduction:Phenylketonuria (PKU) is a rare genetic inborn error

of protein metabolism that is detectable during the first days of life with appropriate blood testing (newborn screening). The absence or deficiency of an enzyme that is responsible for processing the essential amino acid phenylalanine characterizes PKU. With normal enzymatic activity, phenylalanine is converted to another amino acid (tyrosine), which is then utilized by the body (aprecursor of epinephrine, thyroxine an melanin). However, when the phenylalanine hydroxylase enzyme is absent or deficient, phenylalanine abnormally accumulates in the blood and is toxic to brain tissue. Phenylalanine is used in different biochemical processes to produce neurotransmitters, dopamine, norepinephrine, and epinephrine.

II. Precipitating Factor: PKU is inherited as an autosomal recessive trait. In other words, two people who conceive a child must both be carriers of the gene in order for there to be a chance that their infant will have PKU. When both carriers conceive a child, there is a one in four or 25% chance for each pregnancy that the baby will have PKU.

The child fails to meet average growth standards because of the lack of throxine production, restricted weight gain and osteopenia.

Tyrosine is necessary for building body pigment and is incorporated into thyroxine. Without it, body pigment fades and the child becomes fair skinned, light blond haired, and blue eyed.

Abnormally small head(microcephaly), hypersensitivity, developmental delay and even death.

The metabolite phenylpyruvic acid (a breakdown product of phenylalanine) spills into the urine to give the disorder its name. It causes urine to have its typical mousy odor.

III. Signs and Symptoms

Many children develop an accompanying seizure disorder . The skin is prone to eczema and alopecia (Atopic dermatitis).

Many children develop an emotional agitation, confusion, depression, decreased alertness, decreased memory and behavioral changes.

IV. Possible Complications:People with PKU who are not following the PKU diet can become deficient in biotin, a water-soluble B vitamin. This is because phenylalanine blocks biotin metabolism. In a controlled study of children with PKU, elevated phenylalanine levels resulted in seborrheic dermatitis caused by biotin deficiency, which was corrected by a return to the phenylalanine-restricted diet. Vitamin B12 is found almost exclusively in foods of animal origin, which are restricted on the PKU diet. People on the PKU diet who are inconsistent in their use of a vitamin B12 supplement may become deficient in this vitamin. In a survey of young adults with PKU, 32% were found to have low or low-normal blood levels of vitamin B12. Vitamin B12 deficiency can cause anemia and nerve problems.  

Because the PKU diet is low in animal products, fat intake is also significantly reduced. The results of a preliminary study of children with PKU suggested that the low-fat PKU diet intake may impair the absorption of vitamin K, a fat-soluble vitamin, from the diet, possibly resulting in a vitamin K deficiency. In that study, children with PKU on a strict diet had low levels of certain vitamin K-dependent proteins needed for normal blood clotting. Albinism- The persons lack in the tyrosinase enzyme system which is required for the conversion of 3, 4-dihydroxyphenyl alanine (DOPA) into melanin pigment inside the melanocytes. In an albino patient melanocytes are present in normal numbers in their skin, hair, iris, etc., but lack in melanin pigment. Alkaptonuria- The persons fail to produce the enzyme homogentisic acid oxidase which catalyzes the oxidation of homogentisic acid. Therefore, in them, normal oxidation of homogentisic acid into water and carbon dioxide does not occur and large amounts of homogentisic acid are excreted in the urine, which turn black upon exposure to the air.

In children who did not start receiving treatment for PKU until they were 20 to 40 days old, the benefits of breast-feeding, over formula feeding, was apparent and breast milk appeared to confer some extra benefits to such children born. This is demonstrated easily through higher IQ scores of PKU children who had been breast fed during a preliminary study, the other kids with phenylketonuria who had been formula fed scored lower; these test were of course carried out before these children started on similar restricted diets. Another interesting fact is that the accumulation of the trace molybdenum mineral is often observed in infants with PKU; this abnormal accumulation of molybdenum is universal in kids with PKU. This is another reason breast feeding is initially important, many of the formulas are reinforced with molybdenum far exceeding levels found in breast milk and hence newborns with phenylketonuria who are fed formula milk run the very real risk of accumulating too much molybdenum in their bodies.

Phenylketonuria Test(PKU Test, Guthrie Test,

Phenylalanine)

Testing is done either on the serum (Guthrie test) or on the urine. Testing is not valid until the newborn has ingested an ample amount of the amino acid phenylalanine, which is found in human and cow’s milk. Two or three days of intake are usually sufficient for the Guthrie test. Urine PKU testing is usually done after the infant is 4 to 6 weeks old.

It determines the phenylalanine level in the blood should be done on the second or third day of life is a screening test done to identify elevated phenylalanine levels. Phenylalanine level is usually 20-40 mg/dl in comparison with normal levels of 4-6 mg/dl.

DESCRIPTION

V. Diagnostic Procedure

PROCEDURE AND NURSING RESPONSIBILITIES

Pre-Procedure:• Explain the purpose of the test to the mother and the need for a blood sample to be obtained.• No fasting is required prior to the test.

ProcedureFor Guthrie (serum) test•Warm sites with soft cloth, moistened with warm water up to 41°C, for three to five minutes.Rationale: To easily obtain blood sample.

•. Cleanse site with alcohol prep. Wipe DRY with sterile gauze pad.Rationale: To have a sterile area for puncture.

• Blood is collected by pricking the baby's heel.Rationale: Puncture in heel, it is where blood samples are taken from infants. Wipe out first drop of blood since it is not clean.

. This is then used to cover four circles on an absorbent card, which is then forwarded to the public health laboratory.

Post-Procedure:• Apply pressure on the newborn’s heel for 5 to 10 minutes and then leave the site open tothe air for healing.

How Does Guthrie Test Work??A microbiological assay for the presence of phenylalanine,

phenylpyruvate, and phenyllactate in blood or urine: compounds present in excess in the blood or urine of patients with PKU.

The test uses the growth of a strain of bacteria on a specially-prepared agar plate as a sign for the presence of high levels of phenylalanine, phenylpyruvate, and/or phenyllactate.

The compoundB-2-thienylalanine will inhibit the growth of bacterium Bacillus subtilis (ATCC 6051) on minimal culture media.

If phenylalanine, phenylpyruvate, and/or phenyllactate is added to the medium, then growth of Bacillus subtilis is restored.

If a suitably-prepared sample of blood or urine is applied to the said agar plate, the growth of the bacteria in the test will be a positive indicator for PKU in the patient.

If concentration high enough (as with the excess levels seen with PKU), bacteria will grow under the disc, but not elsewhere.

Generally overnight incubation is enough to determine whether phenylalanine, phenylpyruvate, and/or phenyllactate are present in unusual concentrations in blood or urine.

THERAPEUTIC MANAGEMENT

MEDICAL MANAGEMENTThere are no known drugs or surgical management that would help in treating the disorder. Treatment is a low-phenylalanine diet that must be continued throughout life. The infant receives a special formula, such as Lofenalac, which is low in phenylalanine, and low protein foods are introduced when solid foods begin. Dieticians may recommend that small amounts of milk may be added to the infant’s diet so the child does receive some phenylalanine, as this is essential for cellular growth and body repair. Foods high in phenylalanine content are those rich in protein sources such as eggs, meat, and milk. The child will undergo strict diet. The diet is primarily fruits, vegetables, and starches with a phenylalanine-free protein supplement given to provide sufficient protein for growth.

Human breast milk is fairly low in phenylalanine content. The ideal for most infants with PKU is to be fed some breast milk (so that the many benefits can be obtained), while adjusting the diet appropriately. Babies receive a measured amount of phenylalanine-free milk and an adjusted amount of breast milk. Phenylalanine levels need to be monitored.