The membrane consists of a very thin sheet of fatty molecules (the 'lipid bilayer'), which acts as a seal, supported by a network of protein molecules known as the cytoskeleton. It is like a sheet of plastic supported by chicken wire. Studs in the sheet of plastic attach it to the support below. Other inherited haemolytic anaemias, hereditary spherocytosis and hereditary elliptocytosis, are caused by problems in the supporting network; stomatocytosis is a problem with the sealing sheet.
The red cell, like all other cells, tends to take on water, pulled in by a process known as osmosis. The cell has to counter this tendency, and it does so by manipulating the movements of the ions sodium and potassium. A protein called the 'sodium pump' is embedded in the membrane and this protein uses energy to force sodium ions out of the cell and potassium ions in. The action of this pump is pitted against a non-energy-consuming 'leak', which is abnormally high in the hereditary stomatocytoses as defined here.
A 'gene' is a stretch of DNA on a chromosome which codes for a protein. It is made of a very long string of 4 similar molecules ('bases', labelled A,C,G and T), like coloured beads on a string, and the ordering of these bases determines the nature of the protein for which the gene codes. The gene itself does nothing except be copied. It is the master design, with control switches, for proteins. Errors creep into these sequences and it is a series of such errors that cause inherited diseases. There are about 50,000 genes in the human collection.
The packaging system for genes. Humans have 23 pairs of 'autosomes', the chromosomes that are common to both sexes, and two sex chromosomes, X and Y. Females are XX and males, XY. Each chromosome contains a quantity of DNA and very many genes, which are arranged in a line.
A protein is made of 'amino-acids' which are small molecules (there are 20) with different sizes and electrical charge. Like the bases in DNA, these are arranged in a long chain, and the sequence of the protein is determined by the sequence of the gene that codes for the protein. The amino-acid chain folds up into some definite shape&emdash;long and thin or short and fat&emdash;and then 'does something'. It might act as a building block, or the cement, or the setter of the cement, or the pourer of the cement, or the tap that controls the pourer, or the arm that lifts the pourer, or ... well, they can do a lot of things. Message is that while genes act as designs, it is the proteins that do the doings.
When common salt, which is sodium chloride, dissolves in water, the atoms of sodium and chloride immediately separate and go their different ways in the liquid. It happens that the atoms become electrically charged in this process: sodium loses one electron and becomes positvely charged, while chloride gains an electron and becomes negatively charged. The body, and in particular the membrane pumps that we are concerned with here, deal with these in a particular way: hence the 'sodium-potassium pump', the protein that shifts these ions across the membrane. Different proteins deal with the chloride, but these need not concern us here.
Mapping is an approach to genetic problems which exploits the fact that the genes are arranged in lines on the chromosomes. When the rearrangements take place which mix the genes that we inherit, the long lines of genes derived from the grandparents are laid out beside eachother, like the two carriageways of a motorway. Then, at some random point along the motorway, the two strands are cut and switched over. Thus we inherit all the way from North down to the cut point from grandad and all points south from grandma. If you can find this cut point, you can predict what is happening above and below. It's powerful. Since this cut point is random, individuals vary, and the different cut points in different people can be used to narrow down the interval on the chromosome where the problem must lie. Thus we like to find big families (you know who you are!) who have these conditions. Barry, Catherine, Jennifer, Matthew, we love you all.
The normal red cell survives for about 120 days in the circulation. Apart from hereditary stomatocytosis, there are many other problems which can shorten the lifespan of the red cell, and these conditions go under the name 'haemolytic anaemia'. The cell can be attacked by antibodies ('autoimmune haemolytic anaemia'); or for genetic reasons, a number of proteins (the functioning components) within the cell may not work properly. For instance, its principal protein, haemoglobin, may be faulty, as in sickle cell disease; or one of the proteins that maintains the energy supply may be faulty; or one of the 200 or so proteins of the membrane may be not be working properly. Problems in the other membrane proteins are quite common and end up in conditions known as 'hereditary spherocytosis' or 'hereditary elliptocytosis'.
When the red cell breaks down too soon, its contents have to be dealt with. The vast majority are easily disposed of, or recycled, but one part of the haemoglobin protein molecule is difficult for the body to get rid of because it is not readily soluble in water. This 'haem' material is taken to the liver and chemically altered, but the product accumulates in the circulation because the liver has only a limited capacity to deal with it further. This yellow substance, known as bilirubin, makes the patient appear yellow, especially around the eyes. When this yellow substance passes through the liver into the bile ducts, it can precipitate and form stones&emdash;gallstones&emdash;which cause pain in the upper right part of the abdomen.