How Do I Deal With Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency refers to a disorder or disease that is the result of lack of production or abnormal production of the alpha-1 antitrypsin, an enzyme inhibitor, in the body. Alpha-1 antitrypsin belongs to a family of proteins called as the serine proteinase inhibitor (serpin) family due to similar functions. Such proteins actively aids in managing the inflammation, coagulation, and restore mechanisms of the body. The liver is the major producer of alpha-1 antitrypsin.

In the tissues and blood, there exist some powerful enzymes called as proteases that are capable of attacking unknown substances such as tobacco smoke, present or entering in the body. But, these protease enzymes should be controlled, as they have the potential to attack and harm normal body tissues; instead of the targeted substances. This leads to the condition wherein the local tissues are damaged.

In order to protect the tissues from this attack or damage, the blood and tissues in our body carry a protease inhibitor that does the work of binding the proteases. Alpha-1 antitrypsin is the most common protease inhibitor in the blood whose aim is to block this uncontrolled and possible dangerous protease activity.

Alpha-1 antitrypsin deficiency is believed to be a common hereditary disorder among white population. It is more commonly found across Europe, but the frequency and the type of the deficiency differ. According to a research, the most severe type of alpha-1 antitrypsin deficiency is found across the North Western European seaboard. In Scandinavia, alpha-1 antitrypsin deficiency is seen rarely in 1 per 1600 people, but is even rare in other places.

Alpha-1 Antitrypsin Deficiency Causes

The alpha-1 antitrypsin deficiency is considered as a hereditary disorder that is the result of a defect in the gene of chromosome 14. A gene is the sequence of DNA present in chromosomes that exist in the cell’s nucleus.

According to the results of the laboratory tests and medical research on the types of this deficiency, above 70 different variants are discovered among which the normal alpha-1 antitrypsin is indicated as M. Each child takes over two replica of chromosome 14. If they are normal, the person is assigned the label of PiMM, where Pi is the short form of protease inhibitor.

If there is any mutation (change) in the alpha-1 antitrypsin gene, two main abnormal variants are produced that are labeled as S and Z. These variants can be in any combination such as SS or SZ. Depending on the variants produced, a person might be designated as PiSS, PiZZ, or PiSZ. This state is medically termed as being homozygous.

Sometimes, an individual might have one normal and another abnormal gene. Then, this person will be designated as PiMS or PiMZ.

It is this heterozygous state that is responsible for the onset of the alpha-1 antitrypsin deficiency.

The Alpha-1 antitrypsin genes are co-producers of the alpha-1 antitrypsin. This means that each of the normal genes produce 50 percent of this protease inhibitor. However, if there is an unusual PiZ gene and another usual PiM gene, the PiZ gene is able to produce only 10 percent of the alpha-1 antitrypsin produced by the PiM gene. This means that the person labeled with PiMZ have 60 percent of the alpha-1 antitrypsin (50 percent from PiM and 10 percent from PiZ) in its blood, which usually suffice to prevent the onset of the disease.

If an individual is designated with PiZZ, the blood of the so-called person only has 15-20 percent of the alpha-1 antitrypsin levels, which is the cause of severe condition of the deficiency.

An individual who is designated as PiSS, both the genes being of the ‘S’ variant, are not inclined towards the serious condition of this disease. But, it can lead to disorders related to lungs, rather than disorders of the liver. This is because the means through which this deficiency results in damaging the lungs and liver are likely to vary.

The Progress of Alpha-1 Antitrypsin Deficiency

The type of abnormal alpha-1 antitrypsin genes that affects the quantity and type of alpha-1 antitrypsin plays an important role in the progress of alpha-1 antitrypsin deficiency. However, the effects of this disease might vary among people having similar genes.

In case of alpha-1 antitrypsin deficiency, both liver and lungs are damaged.

• Alpha-1 antitrypsin deficiency results in emphysema in lungs, which is a persistent progressive disease apparently observable between the age of 30-40 for the ones who smoke and 10-15 years afterwards for those who do not smoke. Over the 15-20 years later, the lung disease may deteriorate slowly that can result in respiratory failure and death.
• Alpha-1 antitrypsin deficiency can also result in jaundice and other liver problems in toddlers just after few days of their birth. Some of these might suffer from quickly progressive disease, but symptoms tend to reduce. Sometimes, in few cases of children, noticeable liver disease occurs prior to the age of 20 due to alpha-1 antitrypsin deficiency. Many a times, the liver problems caused due to this deficiency might be detected only in adulthood. This means that the progress of liver disease is not that predictable. Among people with severe PiZZ variant, there are chances of cirrhosis and liver scarring.

Alpha-1 Antitrypsin Deficiency Symptoms

Listed below are the symptoms of alpha-1 antitrypsin deficiency.

Respiratory (lung) Disease

• Progressive lung damage due to protease enzymes along with other factors as smoking
• Emphysema due to damage of the lung tissue and permanent unusual widening of airspaces at the bottom of the lungs
• Shortness in breathing on exertion and cough in smokers
• Difficulty in breathing at rest over 15-20 years
• Respiratory failure
• Untimely death

Hepatic (liver) Disease

In individuals with PiZZ, who are mostly inclined towards severe liver disease, defective alpha-1 antitrypsin genes might bundle together in the cells of the liver, whose effects are noxious in nature.

Childhood Liver Disease

Alpha-1 antitrypsin deficiency is the genetic reason of liver problems in toddlers and children. The most common effect is the ‘neonatal hepatitis syndrome’ whose onset is in between four days to six weeks from birth. The symptoms of this syndrome include:

• Jaundice
• Pale stools
• Excessive bleeding
• Enlarged liver
• Liver cirrhosis (rare)
• Liver failure (rare)

Mostly, toddlers will show a sign of improvement with jaundice vanishing and normal liver blood tests, which means that an immediate treatment is normally not required. In further years of childhood, victims of alpha-1 antitrypsin deficiency might suffer from the symptoms of chronic liver problems or even liver failure. These symptoms are:

• Jaundice
• Abdominal pain
• Itching
• Swelling of the ankles or stomach
• Enlargement of the liver or spleen
• Bleeding from the gut (serious case)
• Drowsiness (serious case)
• Coma (serious case)

Adult Liver Disease

As compared to the liver diseases in children, the symptoms and liver diseases in adults are not different. But the problem is that the disease is not noticeable until many years. Listed below are the symptoms that are more or less that of the symptoms of liver cirrhosis.

• Jaundice
• Swelling
• Bleeding from the gut
• Coma

One more risk associated with the alpha-1 antitrypsin deficiency is hepato-cellular carcinoma or primary liver cancer, which might be first symptom of this deficiency.

Disease in Alpha-1 Antitrypsin Carriers

Even today, medical experts are not sure as to whether heterozygous carriers, those having one unusual gene, are predisposed towards the development of the liver disease. In some cases, the prevailing liver disease whose cause is not known is considered due to
alpha-1 antitrypsin deficiency. This is because reduced production of alpha-1 antitrypsin along with other factors such as infection, smoking, or alcohol might deteriorate or increase the chances of inclination towards liver diseases.

Alpha-1 Antitrypsin Deficiency Diagnosis

The first step for the doctor to deal with a disease is to diagnose it, confirm it. In case of children, this disease is not that common, so the complaint of any problem related to the liver would stimulate the thought of alpha-1 antitrypsin deficiency as the cause in mind. On the contrary, in case of adults, the presence of this deficiency might just be ignored as there are many other common factors resulting in liver disease.

In reality, most cases are not even diagnosed. To support this statement, according to the research statistics, it is found that approximately 5 percent of U.K. population suffering from alpha-1 antitrypsin deficiency is hardly examined for confirmation.

To detect this deficiency, the blood test is done to identify the alpha-1 antitrypsin levels. If this is low, the next action is to determine the precise alpha-1 antitrypsin variant by examining the cells under the microscope. These cells are mostly taken from a liver biopsy.

It is difficult for your GP to confirm alpha-1 antitrypsin deficiency 100 percent. Therefore, it is done in coordination with the hospital specialists. As the deficiency in genetic in nature,
genetic counseling and tests for the family members are suggested for the victims’ families.

Liver functioning can be examined by blood tests and further scans, while the lung functioning can be assessed through breathing tests, chest X-ray, and CT scans.

Alpha-1 Antitrypsin Deficiency Treatment

In case of children, the GP, hospital specialists, and other centres specializing in liver disease together might treat the deficiency and liver problems, as a liver disease is quite strange in children. In case of adults, GP and hospital specialists can manage to tackle the deficiency. Listed below are the different alternatives to treat alpha-1 antitrypsin deficiency.

• Inhaled medicines and antibiotics to treat emphysema and liver infections
• Therapy for liver cirrhosis and liver failure
• Organ transplantation if the over the time medication or treatment is not effective in preventing the chronic progressive disease of the liver or lungs
• Lung transplantation for the end-stage emphysema
• Liver transplantation for children (rare)
• Periodic infusion of alpha-1 antitrypsin for improving lung disorders, but no guarantee for long time benefit

There is no effective specific therapy to treat alpha-1 antitrypsin deficiency. On a different thought, a research has been done on gene therapy, but the results are not up to the mark and hence the therapy not implemented.

Lastly, the most important advice to keep in mind is to quit smoking.

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