Does the disease have a relatively high incidence?

 Can the disease be detected within days of birth?

 Can the disease be identified by a biochemical marker which can be easily measured?

 Will the disease be missed clinically, and would this cause irreversible damage to the baby?

 Is the disease treatable, and will the result of the screening test be available before any irreversible damage to the baby has occurred?

Congenital hypothyroidism

Primary hypothyroidism is present in one in every 4000 births in the UK. There is often no clinical evidence at birth that the baby is abnormal, yet if congenital hypothyroidism is unrecognized and untreated, affected children develop irreversible mental retardation and the characteristic features of cretinism (Fig 78.3). Most cases of congenital hypothyroidism are due to thyroid gland dysgenesis, the failure of the thyroid gland to develop properly during early embryonic growth. The presence of a high blood TSH concentration is the basis of the screening test (Fig 78.4). In addition to congenital hypothyroidism, iodine deficiency in the mother and/or the baby may also cause babies to be hypothyroid at birth, and to have a high TSH on screening. It is important that these babies are not incorrectly labelled as having congenital hypothyroidism and unnecessarily treated with thyroxine for life.

A positive result of a screening test should be confirmed by demonstration of an elevated TSH in a serum specimen obtained from the infant. When necessary, thyroxine treatment should be initiated as soon as possible after diagnosis. The initial dosage is 10 µg/kg and this can be gradually increased during childhood to the adult dosage of 100–200 µg per day by 12 years of age. The absence of clinical signs of hypothyroidism or hyperthyroidism, together with normal serum T₄ and TSH concentrations, provides evidence of the adequacy of treatment.

If a positive screening test is obtained, the mother’s thyroid function is usually also assessed. Maternal autoantibodies can cross the placenta and block receptor sites on the fetal thyroid. In this rare situation, after an initial transient hypothyroidism just after birth, the baby’s own thyroid function will usually develop normally.

TSH screening does not detect secondary hypothyroidism due to pituitary disease. This is a much rarer disorder than primary hypothyroidism, occurring in one in every 100 000 births.

Phenylketonuria

The incidence of phenylketonuria is around one in every 10 000 births in the UK. Phenylketonuria arises from impaired conversion of phenylalanine to tyrosine, usually because of a deficiency of phenylalanine hydroxylase. Figure 78.5 shows how phenylalanine, an essential amino acid, is metabolized. In phenylketonuria, phenylalanine cannot be converted to tyrosine, accumulates in blood and is excreted in the urine. The main urinary metabolite is phenylpyruvic acid (a ‘phenylketone’), which gives the disease its name. The clinical features include:

Phenylalanine hydroxylase uses tetrahydrobiopterin (BH4) as a cofactor. Defective BH4 supply or regeneration, due to deficiency of dihydropteridine reductase, have been identified as rare causes of ‘hyperphenylalaninaemia’, a term that better describes the group of disorders.

The detection of phenylketonuria was the first screening programme to be established. The screening test is based on the detection of increased phenylalanine concentration in the blood spot.

The mainstay of the management of phenylketonuria is to reduce the plasma phenylalanine concentration by dietary control. Mental retardation is not present at birth, and can be prevented from occurring if plasma phenylalanine concentrations are kept low in the early years of life. It was thought that dietary control need only be followed for 10 years or so but current views are that lifelong therapy is necessary.

Women with PKU can have healthy children provided they maintain strict adherence to a low phenylalanine diet throughout their pregnancy. These women with PKU should have counseling and dietary advice before becoming pregnant and are followed up in specialist clinics after conception. Poor maternal control puts the baby at risk of delayed development, mental retardation, microcephaly, poor somatic growth and congenital defects. Since pregnancy is often unplanned, ideally they should always remain in good control.