Biology of Disease

National Screening Programs for Inherited Diseases

A number of factors need to be considered before a screening program

(Chapter 1) for any inherited disease is instituted. These include:

N does the disease have a relatively high incidence;

N can the disease be detected within days of birth;

N can the disease be identified by a biochemical marker that is easily measured;

N will there be a failure in diagnosing the disease early and would this cause

irreversible damage to the baby;

N can the disease be treated and will the result of any screening test be

available before irreversible damage to the baby occurs?

Thus, for example, neonatal screening programs for PKU are well established

in practically all the countries of the developed world, including the UK.

Any screening program has to be cost effective. Screening for PKU involves

collecting a specimen of capillary blood from the baby at 6 to 10 days

after birth, which allows for sufficient time for feeding and protein intake

to become established. The test involves determining the concentration

of phenylalanine in the plasma. If the result is indicative of PKU, further

definitive tests are performed. The plasma phenylalanine concentration used

to be determined by the Guthrie test, which involves determining the ability

of plasma to support the growth of the bacterium Bacillus subtilis, which can

only grow if phenylalanine is present in the medium. Nowadays, however,

most laboratories use chromatographic, fluorimetric or mass spectrometric

methods for the estimation of phenylalanine.

15.7 Chromosomes and the Human Karyotype

Interphase chromosomes are present as extended structures and cannot be

seen with the light microscope. At the onset of cell division, both mitotic and

meiotic, the chromosomes condense to form compact structures, referred

to as mitotic figures. All chromosomes have a narrowed region called the

centromere that divides the chromosome into two portions and allows them

to be classified as metacentric, submetacentric, acrocentric or telocentric as

shown in Figure 15.18. When the chromosome is divided into two unequal

lengths, the shorter is called the p arm and the longer the q arm. When

stained with Giemsa stain (Figure 15.19), most arms are divided into two

or more regions by prominent bands and each region is further subdivided

into subbands that can be numbered unambiguously. For example, band

Xp21.2 is to be found on the p arm of the X chromosome in region 2, band 1,

subband 2.

X]VeiZg&*/ GENETIC DISEASES

)'- W^dad\nd[Y^hZVhZ

Metacentric Submetacentric Acrocentric Telocentric

p

q

p

q

Satellite

Stalk

Centromere

Figure 15.18 A classification of chromosomes

into metacentric, submetacentric, acrocentric and

telocentric types based on the position of the

centromere.