18.04.07 Newborn screening

Question 1

When was the newborn screening programme introduced. Which conditions are currently tested for?

Answer 1

Intoduced in 1969 - PKU, 1981 - Hypothyroidism.

1. Phenylketonuria (PKU)
2. Congenital hypothyroidism (CHT)
3. Sickle cell anemia/disease (SCD)
4. Cystic fibrosis (CF)
5. Medium chain acyl-CoA dehydrogenase deficiency (MCADD).
6. Maple Syrup Urine Disease (MSUD)
7. Homocystinuria (pyridoxine unresponsive) (HCU)
8. Glutaric Acidaemia type 1 (GA1)
9. Isovaleric Acidaemia (IVA)

Question 2

What is the incidence, gene association and clinical features of PKU?

Answer 2

1 in 10,000 in UK
PAH (12q23.2) mutations
PAH encodes phenylalanine hydroxylase necessary for Phe –> Tyr. No PAH = toxic build up of Phe.
Mental retardation will result if left untreated.

Question 3

What is the biochemical test for NBS PKU?

Answer 3

Tandem mass spec used to measure absolute conc of Phe and Tyr.
Ratio calculated
Raised Phe = ?PKU
Raised Phe + Tyr = ?Galactosaemia

Question 4

Describe the role of genetic testing in the NBS for PKU.

Answer 4

Not usually a routine part of the programme as prenatal testing is not encouraged for this treatable condition.

PAH genetic testing may be useful following diagnosis to identify mutations that may be amenable to specific treatment e.g. BH4 supplementation

Question 5

What are the advantages of genetic screening for PKU?

Answer 5

Identified babies can be treated early through special diet preventing severe disability.

Early diagnosis and treatment reduces risk of neurological handicap 80/90% –> 6-8%

Patients who are identified later may see no benefit from a modified diet.

Question 6

What is the incidence, physiology and clinical features of congenital hypothyroidism?

Answer 6

Thyroid gland does not produce thyroxine

1 in 4,000 babies

Growth retardation and may develop irreversible mental disability.

Low hair-line, protruding tongue, cold skin, jaundice, feeding difficulties, constipation and sluggish behaviorurs.

Question 7

What are the different aetiologies of CHT?

Answer 7

Primary CHT: absence or abnormal development of thyroid gland (can be ectopic), may be caused by maternal anti-thyroid medication.

Can also be the result of a non-function thyroid or dimished capability of producing thryoxine