You have been told by your doctor that your child has alpha-1 antitrypsin deficiency and that there may be some problems with his or her liver. This webpage attempts to explain, using the minimum of technical terms, what your doctor or hospital consultant may have discussed with you. Nothing written here should be taken as a substitute for what he or she has said to you.
The next two sections briefly explain the background to your child’s condition.
The liver is the largest gland in the body the only organ that can repair and re-grow itself after damage. It performs many complicated functions varying from cleansing the blood of poisons to manufacturing bile to assist in the digestion of fat in our diets. It helps with the breakdown of carbohydrates in our food into a form that allows a quick release of energy when needed. This is why people with liver damage may lack energy.
The liver has many functions relating to keeping the blood clean and healthy:
- Removal of worn out red blood cells by re-using them in making bile which is used by the body to digest food.
- Regulation of blood sugar.
- Helping the body to destroy poisons such as alcohol and other unwanted substances.
- Removal of excess amino acids in the blood by breaking them down to be passed out in urine.
- Controlling the level of fats in the blood by making cholesterol.
- Making proteins to help the blood clot (coagulants) and others to keep the blood from thickening too much (anticoagulants).
- Making and regulating the level of many hormones.
- Producing alpha-1 Antitrypsin which protects the body from the activity of the enzymes released from white blood cells when the body is attacked by infecting agents such as germs, viruses and chemical irritants.
What is Alpha-1 AntitrypsinDeficiency?
Alpha-1 antitrypsin deficiency (AATD) is a hereditary condition that occurs predominantly in people of European extraction. In the United Kingdom about one in 2,500 people have this condition. It is the most common genetic cause of pulmonary emphysema in adults and liver disease in children.
People with AATD either do not produce enough of the alpha-1 antitrypsin protein or the protein produced is abnormal and it accumulates in the liver and is not released into the bloodstream. What is a deficiency in the rest of the body is often a surplus of badly formed alpha-1 antitrypsin in the liver.
Most people with AATD do not have liver disease; others have severe disease which can lead to scarring (cirrhosis) of the liver. The reasons for this variability are not fully understood. In addition, there is evidence that infants, young children, and school-age children with the deficiency also have an increased likelihood of developing bronchial disease. According to current data, only around 2 to 5% of Alpha patients are affected by liver disease in adult age.
New-born babies can show signs that their livers are not functioning properly – jaundice, pale stools, dark urine, etc. This is not unusual. Even babies with AATD can, and often do, become normal healthy babies after a period of neonatal jaundice. However, if it known that the baby is a possible Alpha and these signs persist, hepatologists (specialists in liver diseases), gastroenterologists and paediatricians will investigate further and endeavour to help in this complex clinical area. They will measure the level of alpha-1 antitrypsin (AAT) in the baby’s blood and other chemicals related to liver function From this they will choose the most appropriate treatment and also make an estimate of the likely progression of the condition. If the level of AAT is very low they may make further tests to see if the baby is alpha-1 antitrypsin deficient.
Generation to Generation
Our ability to make AAT is inherited through genes passed on by both parents. We have about 25,000 pairs of genes in every cell of our body. Our genes determine how our bodies grow and develop. One of these genes is known as Protease Inhibitor (Pi). It is this gene that makes AAT.
We all have two copies of the Pi gene. We inherited one copy from our mother and the other from our father. When we have a child we pass one of our Pi genes, and our partner provides the other.
There are more than 75 different varieties of the Pi gene. Most of these varieties result in normal levels of AAT in the blood, but some result in low levels or no AAT. The most common varieties are labelled M, S and Z.
- Most people have two copies of type M (written PiMM) and have normal levels of AAT in their bloodstream.
- Type Z results in low levels of AAT in the bloodstream and someone with two copies of the Z type (PiZZ) has AAT deficiency.
- Someone with one copy of type Z and a copy of type M (PiMZ) is a carrier of AAT deficiency.
- Type S results in slightly reduced levels of AAT, so someone with PiMS will probably have less AAT than someone with PiMM but more than someone with PiMZ.
Your child has been diagnosed as being an Alpha, i.e. having two Z genes. This means that you and the other parent of your child are at least carriers of the Z gene.
In this case the probability of your child being an Alpha was one in four. If you or your partner is an Alpha (PiZZ) then this increased to one in two. In the extremely rare case that both of you are Alphas then all your children will be Alphas.
Diagnosis of Liver Problems
A correct diagnosis can only be made by a trained hepatologist or gastroenterologist but here are a few signs that you may notice.
- Jaundice. Spent red blood cells break down to produce bilirubin. A damaged liver cannot process bilirubin which consequently builds up in the blood and this causes the skin and the whites of the eyes to appear yellow. Urine becomes darker but stools may be light in colour because they contain less bilirubin than usual.
- Severe itching. This is caused by bile products being carried to the surface of the skin.
- Swelling of the abdomen by the accumulation of water. This is termed ascites.
- Easy bleeding or bruising of the skin.
- General failure to thrive.
Remember, jaundice is quite common in new-born babies so do not take this sign (or any of the others) in isolation as indicating liver problems. The type of jaundice related to the liver problem is different and can be distinguished by a simple blood test.
You may already know that you or the other parent of your child is an Alpha or a carrier of AATD. These facts are also helpful in confirming the diagnosis. But even then most Alpha children do not suffer from major liver failure and so your doctor may resort to Liver Function Tests to determine the best treatments.
Liver Function Tests
This section explains what some of the standard tests are measuring. It may also make you familiar with some of the long chemical names and their abbreviations used by physicians.
Alanine aminotransferase (ALT) and aspartarte aminotransferase (AST) are enzymes that are present in the liver cells. They leak into the blood stream when the liver cells are damaged. Alkaline phosphatase (ALP) is an enzyme found mainly in the bile ducts of the liver. Increases in ALP and another liver enzyme called gamma glutamyl transferase (Gamma GT or GGT) can indicate obstructive or cholestatic liver disease. This is when bile is not properly carried from the liver because the bile duct is blocked. GGT and ALP are tested together to check that ALP increases are coming from the liver and not from other sources.
Bilirubin has already been mentioned as an indicator of liver disease. Another important protein that may be tested is albumin. This is an important protein that helps keep fluid pressures in the body stable and carries many substances in the body. Albumin levels may be low for a number of reasons and so it is only used to corroborate the other tests.
The liver makes proteins which clot the blood which is a useful feature when we suffer cuts and abrasions. A damaged liver may not produce the proteins in sufficient quantity and so the blood becomes thin and the skin bruises easily. The test is a simple measure of the time that the blood takes to clot – the prothrombin time.
Many of the substances tested can have abnormal levels or values for reasons not directly connected with the liver. In addition, normal healthy livers can from time-to-time produce substances in excess or deficiency. Even when liver damage is suspected the blood tests are not always able to reveal the full extent. The two main techniques used to resolve this are biopsies and sonar scans.
A liver biopsy is a direct method of assessing the extent of liver damage. A special needle is passed through the skin from the side then between the lower ribs to sample tissue from the liver. The specimen sample is then examined under a microscope by a specialist.
A sonar or ultra-sound scan is less invasive. It shows the size of the liver and adjacent organs and assesses their blood supply and the presence of any unusual lumps.
There is no single treatment that can be prescribed for liver damage in children caused by AATD.
In mild cases of liver distress the treatment may be to relieve the side effects. Fluid build up in the abdomen may be reduced with a diuretic drug or by paracentesis which is the direct removal of the fluid by needle.
Drugs may be used to correct imbalances in the levels of substances processed or created by the liver. This is a complex area and each child is different and so the hepatologist will make a judgement on a case by case basis.
The liver processes many of the constituents of the food that we eat and so it is essential to follow dietary advice from your hepatologist or specialist dietician.
The general aim is to place low stress on the liver but to provide sufficient nutriments to help the body thrive.
- Good amount of fresh fruits and vegetables.
- A restricted amount of protein, especially animal protein, as a diseased liver cannot metabolise protein well.
- Slightly more carbohydrate than usual in the diet. This is to compensate for the reduced ability of the liver to convert carbohydrates to glycogen which supplies energy to other organs. This is the underlying reason why liver patients often feel very fatigued.
- There should be strict restriction of fat intake as fat can cause more damage to a diseased liver.
- You may be advised to restrict fluids and salt. The sodium in salt helps in retaining water. Liver patients with ascites (accumulation of fluid in abdomen) will feel worse if they consume too much water and sodium.
There may be other conditions or intolerances that must be taken into account when planning a balanced diet and these general guidelines may be varied to account for these.
There is no procedure or drug that can repair a damaged liver. In extreme cases of liver failure the only option is a transplant.
A Transplant Co-ordinator may be appointed to check the availability of suitable livers for a sick child. This may take time during which the hepatologist will monitor liver functions and continue to give medication to control the symptoms.
Living donor transplant is also a possibility where a suitable healthy adult is prepared to donate a part of his or her liver. This is an increasingly popular option for liver transplantation in children.
A piece of the donor’s liver (from the small bulge on the left-hand side) is removed during a simple surgical procedure and transplanted into the recipient child. The donor’s liver will regenerate itself to full size in a few weeks and show no signs of impairment. The liver in the child will grow normally.
Living donor transplants are elective operations. There is time to plan these operations in detail and schedule them for times convenient to the donor, recipient and medical staff. Most importantly the donated liver section is outside the body for a very short time and is in the best possible condition for the transplant.
Experience has shown that the risks to the donor are minimal for what is a relatively simple surgical procedure. However, since AATD is a genetic condition some close family members may be Alphas and not be ideal candidate donors.
Caring for Your Child
As your child grows you will want him/her to have the best opportunities to cope with, and overcome, possible complications stemming from alpha-1 antitrypsin deficiency.
If your child has liver problems or has received a transplanted liver then your medical specialists will have given you instructions on signs to look for and advice on how to respond when you see them.
As a responsible parent of a young child you must make decisions on your child’s behalf just as an adult Alpha would make for himself. Amongst other things this means avoiding smoke and fumes, staying away from people with colds, etc.
Do not be overprotective of your child. A child brought up to think of himself/herself as ‘sickly’ is starting out at a disadvantage. Many Alphas live long and healthy lives provided that they take sensible precautions. A positive attitude is important and the condition should not be taken to be an unmanageable burden.
As you child grows up he or she should be slowly informed of the do’s and don’ts of life as an Alpha. Starting early with the habit of eating and enjoying a nutritious diet is a gift that will last a lifetime. Pass on the knowledge that smoking is particularly dangerous for Alphas – and that this extends to passive smoking. An understanding of this may help your child resist peer pressures in teenage years. Total avoidance of alcohol is essential for liver affected Alphas.
. . . and Caring for Yourself
Your child is an Alpha therefore you and your partner are at least carriers and you could even be Alphas. If you have not already been tested then ask your doctor to perform the tests. If you are uncertain about any part of this then he/she may recommend that you see a genetic counsellor.
Some Alphas live their lives and have no symptoms of emphysema or liver failure. This may be due to chance but most Alphas follow a few simple guidelines to help chance along. Even carriers of AATD will benefit from them.
- Keep your body healthy with a balanced diet and regular exercise. Infections and other illnesses are more challenging to Alphas than to most people. Improve your defences.
- Smoking is especially harmful for people with AATD. Tobacco smoke releases increased amounts of the lung-damaging enzyme, thereby destroying more lung tissue. In addition, the smoke destroys what little AAT may be present in the lungs. If you smoke, you should quit as soon as possible. Certainly it is no easy matter to stop smoking, but you can do it. There are programmes to help you kick the habit and your GP will be able to advise you further. Even passive smoking is harmful. Ask everyone who smokes near you to refrain from doing so.
- Keep away from environmental pollutants such as open fires, petrol fumes, paints and solvents, dust, etc. If there are air-borne irritants or fumes at your place of work then wear a mask.
- Heed any air quality warnings on the radio or television, especially in the hot summer months. If ozone levels are high, try not to venture outside and avoid excessive physical exertion.
- Avoid contact with anyone who has a cold or flu. In addition, try to stay away from crowds and large gatherings, especially in winter.
- Ask your GP if he/she recommends a regular flu vaccination or an occasional vaccination against pneumococcal infections.