Question

Another infant (Patient B) is also being evaluated for suspected PKU. BH, loading tests are performed on both patients and the results are presented below. *BH, loading test: Tablets of synthetic cofactor are dissolved in 20 ml of water in dim light and administered to the patients at least 30 min before a meal. Blood was drawn before, and 4 and 8 hours after BH, loading; Phe levels are determined. How would you summarize the results of this test for Patient A and Patient B? Patient A Patient B Phe mg/dL Time (hrs) after BH4 administration

(for patient A the birth weight was 5.9 lbs, and the birth was normal..... newborn screening demonstrated Phe level of 6.6 mg/dL .... Phe dietary restriction was initiated and plasma phenylalanine levels dropped to normal range( 1.65 mg/dL)

Answer 1

Phenylketonuria is an autosomal recessive disorder characterized by deficiency of enzyme phenylalanine 4 hydroxylase which is essential for conversion of phenylalanine to tyrosine. Due to this phenylalanine retain in the blood in high levels and can cause neurological manifestations such as seizures, decreased iq , mental retardation in newborn . This can be identified by detecting  the level of phenylalanine in the blood in new borns so that early treatment can be started and complications can be minimized.

Pku exist as 4 types according to phe level in the blood . The normal range is 0.6 to 2 mg/dl in infants .when there is an increase above the level they are classified as

• Hyperphenylalaninemia
• Mild pku
• Moderate pku
• Classical pku

Most common method to treat these patients ,, is dietary restriction of phenylalanine. Thus high protein content foods are restricted . The disadvantage is, the patient may also develop vitb12 , calcium, vit D , and folic acid deficiency.  

Thus to avoid these disadvantages ,, bh4 loading test is performed to find responses in patients with pku at an eary stage .

Bh4 is tetrahydrobiopterin a cofactor needed for phenylalanine hydroxylase( PAH) to convert phenylalanine to tyrosine

In some patients PAH may be present but bh4 is deficient which may lead to pku . So in these patients administration of bh4 as a supplement will  reduce the level of phenylalanine in the blood .

IN THE ABOVE CHART :

Patient B : who was given bh4 loading dose showed decrease in phe values after 4 hrs and 8 hrs which indicates the patient is responsive to bh4 treatment and bh4 supplement can be given without any dietary restriction to treat the underlying pku which is mild .

Patient A is already diagnosed with pku and was on phe restriction ,, showed slight elevation in pku value after 4 hrs and 8hrs following the bh4 loading dose and meal . This indicates the patient suffer from severe form of pku. And bh4 supplement is unresponsive to this patient . And patient B should continue strict dietary restriction of phenylalanine.