Endocrine/ Metabolic Flashcards
What is phenylketonuria (PKU)?
Phenylketonuria (PKU) is an inborn error of amino acid metabolism (the most common in the UK) caused by absent or virtually absent phenylalanine hydroxylase (PAH) enzyme activity. This enzyme converts dietary phenylalanine to tyrosine. The products of this metabolic pathway are important in the formation of catecholamines, neurotransmitters and melanin.
What is the consequence of an excess of phenylalanine?
High plasma concentrations of phenylalanine lead to the formation of the byproducts phenylpyruvic acid and phenylethylamine, which are thought to be neurotoxic above a threshold concentration.
Presentation of a child with PKU:
- Most children appear normal at birth and diagnosis usually occurs through an abnormal result in the heel-prick blood assay.
- Children tend to be very fair with pale blue eyes if compared to siblings or general family colouring.
- In undetected cases, children often give off a musty or ‘mousey’ odour.
- Progressive developmental delay and general learning disability are the usual modes of presentation in those not detected by screening.
- Diagnosed children who cease dietary manipulation may show deterioration in motor skills and cognitive function; there may be MRI evidence of demyelination.
- Recurrent vomiting.
- Eczematous skin eruptions, scleroderma-like skin lesions
- Seizures.
- Self-mutilation and severe behavioural disturbance.
- Untreated older children may be hyperactive with rhythmic rocking and writhing movements classically affecting the hands, face and tongue.
Name the different classifications of PKU:
Type I, or classical, PKU: Inherited in an autosomally recessive fashion.
Type II: There are cases of hyperphenylalaninaemia (HPA) where up to 5% of enzyme activity is retained, due to less critical mutations in the enzyme’s sequence, or differing phenotypical expression. These patients tend to have less serious disease that presents later in life and their optimal treatment is less clear-cut.
Malignant PKU: There is a variety of PKU due to a deficiency in the synthesis or metabolism of the enzyme’s co-factor tetrahydrobiopterin (THB), important for the hydroxylation of tyrosine and tryptophan. Such patients tend to develop more severe neurological disease that is not fully responsive to dietary manipulation.
Investigations needed in suspected PKU:
- Heel-prick blood should be assayed for phenylalanine in all UK-born newborns.This test should be carried out at >12 hours after birth.
- Blood levels of phenylalanine above a threshold value (usually around 120 μmol/L) suggest the diagnosis and prompt re-testing and/or formal assay by a specialist laboratory and assessment by a metabolic disease service.
- Tyrosine and THB assay may form part of specialist investigations.
- The disease may be detected during aminoaciduria screening for older children with developmental delay or general learning disability.
Where and who should manage PKU?
Specialist metabolic/ paediatric clinic
Where and who should manage PKU?
Specialist metabolic/ paediatric clinic
Dietician input is necessary
What is the mainstay of treatment for PKU?
Dietary protein restriction of phenylalanine combined with dietary substitution of proteins containing a balanced mixture of amino acids, including a generous supply of tyrosine. These include special low protein foods.
-Regular assay of plasma phenylalanine level, along with levels of its metabolites, are used to assess and monitor response to therapy.
Is breastfeeding ok in PKU?
Yes. Breast feeding is encouraged as breast milk is relatively low in phenylalanine. Breast feeding is used in combination with a special baby milk which does not contain phenylalanine.
What advice do pregnant women with PKU need?
It is very important that pregnant PKU patients who are not strictly adherent to their diet should resume it. Studies suggest that untreated PKU in pregnancy is associated with microcephaly, intellectual disability and attention deficit hyperactivity disorder
What advice do pregnant women with PKU need?
It’s recommended that all women with PKU plan their pregnancies carefully. You should aim to follow a strict diet and monitor your blood twice a week before becoming pregnant. It’s best to try to conceive once phenylalanine levels are within the target range for pregnancy.
During pregnancy, you’ll be asked to provide blood samples 3 times a week and will be in frequent contact with your dietitian.
It is very important that pregnant PKU patients who are not strictly adherent to their diet should resume it. Studies suggest that untreated PKU in pregnancy is associated with microcephaly, intellectual disability and attention deficit hyperactivity disorder
Prognosis in PKU:
-Worsening intellectual disability and developmental delay in infancy and childhood if untreated.
Many adults with PKU find they function best while on a low protein diet. The current advice is for people with PKU to remain on a low-protein diet for life.
Unlike in young children, there isn’t any evidence yet that high phenylalanine levels cause any permanent brain damage in adults with PKU. Some adults decide to resume a normal diet. As a result, they may find they don’t function as well. For example, they may lose concentration or have a slower reaction time. These adverse effects can usually be reversed by going back on to a stricter diet to bring the phenylalanine levels down again. Anyone who returned to a normal diet should still be supported by their clinicians.
What diet should be maintained in PKU?
Avoiding protein rich foods like meat, eggs and diary and controls the intake of many other foods, such as potatoes and cereals. Supplementation of iron, vitamins and minerals may be necessary for those on the diet.
There are also a number of specially designed low-protein versions of popular products (such as flour, rice and pasta) specifically designed for people with PKU and related conditions to incorporate into their diets. Many of these are available on prescription.
If a high phenylalanine level is confirmed, a baby will immediately be started on a low-protein diet and amino acid supplements.
Phenylalanine levels in the blood are regularly monitored by collecting blood from a finger prick on to a special card and sending it to a laboratory.
Your dietitian will draw up a detailed dietary plan for your child that can be revised as your child grows and their needs change.
What is congenital hypothyroidism?
Congenital hypothyroidism (CH) can be defined as a lack of thyroid hormones present from birth. If it is not detected and treated early it is associated with irreversible neurological problems and poor growth.
What is childhood hypothyroidism?
Some infants develop a lack of thyroid hormones after birth. This is thought to represent primary hypothyroidism rather than CH. Children with untreated primary hypothyroidism do not experience the irreversible neurological problems that are seen with untreated CH.
