In many cases, signs and symptoms of AAT deficiency do not show up before the individual is above the age of 30 years. However, some individuals who smoke tend to develop symptoms in their early 20s. AAT deficiency gravely affects the functioning of the lungs and the liver. The signs and symptoms include the following:

• Shortness of breath
• Wheezing
• Cough along with sputum
• Chest infections
• Mild liver damage 
• Vision problems
• Unexplained weight loss
• Fatigue 
• Rapid heart rate upon standing

• Fatigue

  Coughing, wheezing, shortness of breath, chest infection, fatigue and unexplained weight loss are some of the grave symptoms of this genetic disorder. [symptoma.com]

  BACKGROUND: The benefits of pulmonary rehabilitation (PR) on fatigue-resistant skeletal muscle fibre type I have been found to be smaller in COPD patients with alpha-1 antitrypsin deficiency (AATD) than in those without AATD. [ncbi.nlm.nih.gov]

  The most common adverse reactions during PROLASTIN-C LIQUID clinical trials in >5% of subjects were diarrhea and fatigue, each of which occurred in 2 subjects (6%). Please see full Prescribing Information for PROLASTIN-C LIQUID. [prolastin.com]

• Weight Loss

  Coughing, wheezing, shortness of breath, chest infection, fatigue and unexplained weight loss are some of the grave symptoms of this genetic disorder. [symptoma.com]

  Symptoms of AAT deficiency include Shortness of breath and wheezing Repeated lung infections Tiredness Rapid heartbeat upon standing Vision problems Weight loss Some people have no symptoms and do not develop complications. [medlineplus.gov]

  This causes symptoms such as: Tiredness Loss of appetite Weight loss Yellow color in skin or eyes (jaundice) Swollen belly Swollen legs Blood in vomit or stool In some cases, A1AD may lead to inflammation of fat under the skin. [mountnittany.org]

  This causes symptoms such as: Tiredness Loss of appetite Weight loss Yellow color in skin or eyes (jaundice) Swollen belly Swollen legs Blood in vomit or stool In some people, A1AD may lead to inflammation of fat under the skin. [myhealth.ucsd.edu]

  Unexplained weight loss and chronic respiratory infections associated with fever and rapid heart rate are additional findings that may be reported. As the lung disease advances, emphysema will develop. [texasliver.com]

• Weakness

  There was no correlation between decline in gas transfer and FEV1 for those with COPD, although a weak relationship existed for those without (r=0.218; P CONCLUSION: These data confirm differing individual rates of lung function decline in alpha-1-antitrypsin [ncbi.nlm.nih.gov]

  The Most Common Signs and Symptoms of Alpha-1 Liver Disease Feeling weak and tired Most Alphas have no symptoms of liver disease 41. Testing for Alpha-1 42. [slideshare.net]

  […] effect in those with normal blood oxygen saturations.[3][20] Physiotherapy[edit] Individuals can benefit from a variety of physical therapy interventions.[21] Persons with neurological/neuromuscular abnormalities may have breathing difficulties due to weak [en.wikipedia.org]

  […] recommendations similar to those in the joint statement by the European Respiratory Society and the American Thoracic Society, but the former group capped the age of screening in patients with COPD at 65 years, based on a review of available screening studies (weak [doi.org]

• Anemia

  겸상 적혈구빈혈(Sickle cell anemia) 16. 테이삭스병(Tay-Sachs disease) 17. 윌슨병(Wilson's disease) 18. 판코니 빈혈(Fanconi's anemia) 19. 블룸 증후군(Bloom syndorme) 20. 부신백질 영양장애(Adrenoleukodystrophy) 21. 무감마글로불린혈증(Agammaglobulinemia) 22. 알포트 증후군(Alport syndrome) 23. [hosp.ajoumc.or.kr]

  P74 ) Endocrine, nutritional and metabolic diseases E70-E88 2019 ICD-10-CM Range E70-E88 Metabolic disorders Type 1 Excludes androgen insensitivity syndrome ( E34.5- ) congenital adrenal hyperplasia ( E25.0 ) Ehlers-Danlos syndrome ( Q79.6 ) hemolytic anemias [icd10data.com]

  Treatment, depending on severity of symptoms, typically starts with anticoagulants; the presence of ominous signs (low blood pressure) may warrant the use of thrombolytic drugs.[2] Anemia[edit] Anemia that develops gradually usually presents with exertional [en.wikipedia.org]

• Cough

  Coughing, wheezing, shortness of breath, chest infection, fatigue and unexplained weight loss are some of the grave symptoms of this genetic disorder. [symptoma.com]

  Bronchodilators, drugs that relax the muscles around the small airways and thus widen the airways, such as albuterol may help ease breathing and relieve cough. Lung infections that develop are treated promptly. [msdmanuals.com]

  Patients with alpha 1-antitrypsin (AAT) deficiency, like those with asthma and chronic obstructive pulmonary disease, usually present with dyspnea, wheeze, and cough. [ncbi.nlm.nih.gov]

  Coughing blood Easy bleeding and bruising Skin symptoms Panniculitis are painful lumps or patches on the skin. [medicinenet.com]

• Dyspnea

  Here, we report the case of a 36-year-old Korean woman with AAT deficiency who visited the emergency department of our hospital for the treatment of progressive dyspnea that had begun 10 years ago. She had never smoked. [ncbi.nlm.nih.gov]

  Dyspnea is the symptom that eventually dominates AATD (84%). [1] Similar to other forms of emphysema, the dyspnea of AATD is initially evident only with strenuous exertion. Over several years, it eventually limits even mild activities. [emedicine.medscape.com]

• Pneumonia

  We report a case of panniculitis occurring in a 34-year-old woman with severe AATD following the extravasation of clarithromycin infused intravenously for treatment of community-acquired pneumonia. Resolution occurred with conservative management. [ncbi.nlm.nih.gov]

  Common complications of AATD include pneumothorax, pneumonia, acute exacerbation of airflow obstruction, and respiratory failure. [wikidoc.org]

  They can include: Trouble catching your breath with mild activity Wheezing Tiredness Weight loss A chronic cough with phlegm Chest colds or infections (pneumonia) that happen often A1AD can cause liver disease. [mountnittany.org]

• Sputum Production

  Symptoms The initial symptoms of Alpha 1 antitrypsin deficiency include: Chronic cough Sputum production Wheezing If patients present with wheezing, they're often told that they have asthma. [1stclassmed.com]

  Less common associations are panniculitis and an increase in the association of cytoplasmic antineutrophil cytoplasmic antibody‒positive vasculitis. [5] The initial symptoms of alpha1-antitrypsin deficiency include cough, sputum production, and wheezing [emedicine.medscape.com]

  COPD is characterized by coughing, shortness of breath, sputum production, rapid breathing, wheezing, and weight loss due to the energy required for labored breathing. [en.wikibooks.org]

  Symptoms by affected organ: Lungs Shortness of breath, excessive cough with phlegm/sputum production, wheezing. These symptoms can persist and lead to a decrease in exercise capacity and a persistent low energy state or tiredness. [foundation.chestnet.org]

• Decreased Breath Sounds

  A physical examination may reveal a barrel-shaped chest, wheezing, or decreased breath sounds. [medlineplus.gov]

  […] chest, wheezing, or decreased breath sounds. [ufhealth.org]

  For example, AATD may be suspected when a physical examination reveals a barrel-shaped chest, or, when listening to the chest with a stethoscope, wheezing, crackles or decreased breath sounds are heard. [genome.gov]

• Failure to Thrive

  Other signs in infancy may include: Dark urine, pale stools Itching Enlarged liver Bleeding Fluid build-up in the belly (called ascites) Trouble eating Poor growth or failure to thrive Elevated liver enzyme levels Other children may not show signs of [cincinnatichildrens.org]

  Characteristic features of iron deficiency anaemia in children include failure to thrive (grow) and increased infections. The treatment of iron deficiency anaemia, whether it be in children or adults, is with iron and iron-containing foods. [kmle.co.kr]

  Other symptoms may include: Elevated liver enzyme levels Dark urine and pale stools Itching Enlarged liver Bleeding Feeding problems Poor growth or failure to thrive Diagnosis of Alpha-1 Antitrypsin Deficiency If your child has symptoms of alpha-1 antitrypsin [rileychildrens.org]

  Older children can present as asymptomatic chronic hepatitis, poor feeding, failure to thrive, hepatosplenomegaly, or complications of portal hypertension and cirrhosis. Risk of hepatocellular carcinoma in AAT may be independent of cirrhosis. [unboundmedicine.com]

  Other symptoms may include enlarged liver, bleeding, an abnormal accumulation of fluids within the abdominal cavity (ascites), feeding difficulties, and poor growth or failure to thrive. [rarediseases.org]

• Blood in Stool

  Liver Tiredness, loss of appetite, weight loss, swelling of the feet or belly, yellowish discoloration of the skin (jaundice) or white part of the eyes, vomiting of blood, or blood in stools. [foundation.chestnet.org]

• Jaundice

  Jaundice : what conditions can be associated with jaundice? Last updated 01.10.2014 [netdoctor.co.uk]

  Jaundice in the newborn period can be physiologic and is often due to benign causes. [ncbi.nlm.nih.gov]

  In newborns, AATD causes prolonged jaundice and sometimes perinatal hepatitis that usually resolves by itself. In adults, the liver can be affected, causing fibrosis and sometimes cirrhosis, and in rare cases, malignant hepatoma. [lung.templehealth.org]

  Infants who develop jaundice secondary to alpha-1 antitrypsin deficiency usually have resolution of the jaundice within the first year of life. [rileychildrens.org]

  Affected infants develop yellowing of the skin and the whites of the eyes (jaundice) and an enlarged liver during the first week of life. Jaundice disappears at about age 2 to 4 months. [msdmanuals.com]

• Pulsus Paradoxus

  Airflow obstruction manifests as pursed-lip breathing, wheezing, and pulsus paradoxus. [emedicine.medscape.com]

  Other findings on physical examination include pulsus paradoxus, scalene muscle retraction, intercostal muscle retraction, wheezing, hepatomegaly, hyperinflation results in barrel chest, increased percussion note, decreased breath sound intensity, and [wikidoc.org]

  Cardiac tamponade presents with dyspnea, tachycardia, elevated jugular venous pressure, and pulsus paradoxus.[15] The gold standard for diagnosis is ultrasound.[15] Anaphylaxis typically begins over a few minutes in a person with a previous history of [en.wikipedia.org]

• Tachycardia

  Cardiac tamponade presents with dyspnea, tachycardia, elevated jugular venous pressure, and pulsus paradoxus.[15] The gold standard for diagnosis is ultrasound.[15] Anaphylaxis typically begins over a few minutes in a person with a previous history of [en.wikipedia.org]

• Pruritus

  Alpha-1 antitrypsin testing may be requested when a newborn or infant has jaundice that lasts for an extended period of time (more than a week or two), an enlarged spleen, ascites (fluid accumulation in the abdominal cavity), pruritus (itching), and other [labtestsonline.org.au]

  […] birth including jaundice, swelling of the abdomen, and poor feeding In some children, the signs of alpha-1 antitrypsin deficiency do not become apparent until early childhood or adolescence when they may develop hepatitis, enlarged spleen, ascites, pruritus [en.wikibooks.org]

  Vaccination against hepatitis A and B Medication (Drugs) Ursodeoxycholic acid, a choleretic agent, can be used to manage cholestasis and pruritus in patients with liver disease. [unboundmedicine.com]

  […] however, occur in many liver conditions and are therefore not a reliable clinical feature to distinguish obstruction from liver causes of jaundice.[22] People also can present with elevated serum cholesterol, and often complain of severe itching or "pruritus [en.wikipedia.org]

• Yellow Discoloration of the Skin

  […] disease".[11] Signs and symptoms[edit] The main sign of jaundice is a yellowish discoloration of the white area of the eye (sclera) and the skin. [en.wikipedia.org]

The condition of AATD is usually diagnosed when an individual complains of shortness of breath or is suffering from lung or liver disorders. Lung and liver disease are the preliminary features of AATD.

Blood test to determine the levels of AAT is carried out. In addition, a phenotype blood test is also done to assess the presence of the causing gene. Several other diagnostic tests such as lung functioning tests known as spirometry are done to evaluate the functioning ability of the lungs.

Imaging studies that include an X-ray and CT scan of the chest is also done to further understand the capacity of the lungs. CT scan of the chest would reveal whether the patient has emphysema and its degree of severity. Liver function tests may also be done in order to assess the functioning of the organ.

• Pulmonary Infiltrate

  Then, in May, 2002, she started to present cough, fever and bilateral leg pain and was diagnosed as having CSS on the basis of her past history of allergic rhinitis, pulmonary infiltration, eosinophilia and the presence of antineutrophil cytoplasmic antibody [webview.isho.jp]

• Liver Enzymes Abnormal

  Most of these AATD individuals (83%) are clinically healthy throughout adulthood and most will have liver enzyme abnormalities in early life [ 39 ]. [ncbi.nlm.nih.gov]

  Most of these AATD individuals (83%) are clinically healthy throughout adulthood and most will have liver enzyme abnormalities in early life [39]. [ojrd.biomedcentral.com]

• Hypoalbuminemia

  Diagnostic Tests and Interpretation Lab Elevated total and conjugated bilirubin, elevated serum transaminases, hypoalbuminemia, or coagulopathy Gold standard assessment is protein electrophoresis to determine the protease inhibitor (Pi) phenotype. [unboundmedicine.com]

• Hepatocellular Carcinoma

  Cirrhosis and hepatocellular carcinoma then result in some patients. [ncbi.nlm.nih.gov]

  It can lead to hepatocellular carcinoma. In The Lung The lack of a normal, functioning alpha-1-antitrypsin protein leads to an excess of protease enzymes that attack the connective tissue in the lungs. [zerotofinals.com]

  Hepatocellular carcinoma screening is also needed (more common in males than in females). Liver failure may require transplantation. [patient.info]

  Risk of hepatocellular carcinoma in AAT may be independent of cirrhosis. Fulminant hepatic failure is rare but has been reported. [unboundmedicine.com]

• Liver Biopsy

  A repeat liver biopsy confirmed the presence of a second hereditary disease. This is a unique concurrence of two uncommon genetic disorders. [ncbi.nlm.nih.gov]

  Liver biopsy is not required for diagnosis but can help to support it. [unboundmedicine.com]

So far there is no known treatment plan to cure this genetic disorder. Treatment methods are designed to effectively manage the disease condition and slow down the progression of the disease. Medications form the primary basis of the treatment program. The individual is put on drugs such as a steroids and bronchodilators to help manage the inflammation and flare-ups of emphysema. Antibiotics may also have to be prescribed if the individual is also suffering from infection of the chest. Theophylline that works as a bronchodilator is also prescribed to patients. Augmentation therapy with intravenous alpha-1 antitrypsin protein may afford some benefits for patients with low levels of AAT below 11 µM [8].

Surgery is often the last resort when the patients with COPD develop bullae characterized by large air–filled sacs. Liver transplantation may be required among patients with cirrhosis due to AAT deficiency [9].

Immunizations shots are also given to individuals with emphysema. Some individuals may also be advised to undergo home oxygen therapy. Individuals with recurrent bouts of emphysema may benefit from this. Portable oxygen cylinders are available and oxygen is supplied either through tubes or masks.

The prognosis of the disease condition varies with the degree of symptoms and the pace at which the disease progresses. However, with prompt diagnosis and effective treatment regime, individuals are thought to recover well. The progression of the disease can be arrested and the symptoms put to rest. Since this is an inherited disease condition, it cannot be cured but managed well with appropriate treatment.

Complications

If timely diagnosis and treatment is not initiated, then AAT deficiency can bring along life threatening complications. These include:

• Infection of the chest that worsens the already existing symptoms
• Liver cirrhosis
• Severe emphysema
• Severe bronchitis
• Development of large air filled sacs in patients with COPD.
• Spontaneous pneumothorax [7]

Alpha–1 antitrypsin deficiency is a genetic disorder. If a child inherits two AAT genes from both the parents, then he is said to have developed the AAT deficiency.

The faulty AAT gene that is known to cause the genetic disorder is known as PiZ. Now, if the child inherits one normal AAT gene and one faulty AAT gene (Piz) then he would not suffer from AAT deficiency. However, in such cases, there is a possibility that the child transfers the faulty PiZ gene to the next generation.

About 1.1 million individuals across the globe fall prey to this genetic disease. Earlier it was thought that AAT deficiency is only the disease of Caucasians. However, with in depth research it was revealed that this inherited genetic disorder exists amongst all racial groups. It has also been estimated, that about 3.1 million Americans suffer from COPD.

Of these about 1.9% individuals suffer from COPD as a result of AAT deficiency. Statistics have also revealed that about 1 in every 3000 to 5000 individuals of UK suffer from AAT deficiency. Of the 100,000 person with AAT deficiency in the world only less than 10% are identified clinically [5].

The median time from the instance the symptoms were observed to the time of clinical diagnosis is 8 years making mortality rate for symptomatic patients very high [6].

AAT deficiency is an inherited autosomal disorder that occurs due to mutations in a specific gene that is known to alter the configuration of the alpha–1 antitrypsin molecule. This specific gene is named as SERPINA1 and is located in the long arm of chromosome 14. Alteration of the configuration of AAT prevents its release from the hepatocytes causing a significant decrease in its serum levels. This sequence of events gives rise to the condition related to AAT deficiency.

AAT being an inherited disorder has no prevention. However, early detection of this disease can help in better management of the disease condition. If parents suffer from the same, then diagnosis of their children at an early age can help early initiation of treatment. Making small changes in lifestyle can go a long way in better management of the disease condition. The following practices can be adopted:

• The practice of smoking cigarettes should be discontinued. It not only aggravates the existing condition but also speeds up the development of signs and symptoms of the disease.
• Alcohol should be avoided as it would further aggravate the condition in individuals suffering from liver disease as a secondary complication of AAT.
• The administration of pneumococcal and influenza vaccination have significantly lowered the incidence of emergency room visits of AAT deficient patients with clinical emphysema [10].

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that occurs due to absence of alpha–1 antitrypsin (AAT) enzyme. This heritable disorder predisposes an individual to fall prey to an array of clinical diseases especially early onset emphysema [1]. However, the lungs and the liver are the two main organs that are severely affected. The effects of AATD are not evident until one is of 30 years of age [2].

There is no cure to this disease. The symptoms can however be managed with an effective treatment regime. An estimated 1-5% of adults with chronic obstructive pulmonary disease (COPD) may have AAT deficiency [3]. Although adults AATD cases are more predisposed to emphysema, cases of children with AAT deficiency presenting with emphysema symptoms may occur rarely [4].

Definition

Alpha-1 antitrypsin (AATD) deficiency is an inherited genetic disorder caused due to deficiency of the alpha–1 antitrypsin. This disorder generally affects the lungs and liver of the individual. So far there is no cure to this disease, but with appropriate treatment regime, the symptoms can be managed and the progression of the condition slowed down.

Cause

Two faulty genes of AATD are responsible for the causation of the disease condition. These faulty genes are known as PiZ. If the individual inherits one faulty gene and one normal then he would not develop AATD; however he may pass on the faulty gene to his children.

Symptoms

AATD generally presents lung and liver disorders. Coughing, wheezing, shortness of breath, chest infection, fatigue and unexplained weight loss are some of the grave symptoms of this genetic disorder.

Diagnosis

The condition is usually diagnosed through blood tests that detect the level of alpha–1 antitrypsin. In addition spirometry is also done to assess the lung functioning. Imaging studies that include X-ray and CT scan of the chest are done to evaluate emphysema.

Treatment

Treatment of AATD includes medications that are given to control the wheezing and coughing problem. Antibiotics and steroids are administered to combat the infection and bring down the inflammation.

1. Stoller JK, Aboussouan LS. A review of a1-antitrypsin deficiency. Am J Respir Crit Care Med. Feb 1 2012; 185(3):246-59.
2. Kauppi P, Jokelainen K. Alpha-1 antitrypsin deficiency. Duodecim. 2011; 127(18):1911-8 (ISSN: 0012-7183)
3. Marciniuk DD, Hernandez P, Balter M, Bourbeau J, Chapman KR, Ford GT, et al. Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline. Can Respir J. Mar-Apr 2012; 19(2):109-16.
4. Stoller JK, Lacbawan FL, Aboussouan LS. Alpha-1 Antitrypsin Deficiency. 1993
5. Greene DN, Elliott-Jelf MC, Straseski JA, Grenache DG. Facilitating the laboratory diagnosis of a1-antitrypsin deficiency. Am J Clin Pathol. Feb 2013; 139(2):184-91.
6. Bornhorst JA, Greene DN, Ashwood ER, Grenache DG. A1-Antitrypsin phenotypes and associated serum protein concentrations in a large clinical population. Chest. Apr 2013; 143(4):1000-8.
7. Serapinas D, Obrikyte V, Vaicius D, Balciuviene R, Valavicius A, Sakalauskas R. Alpha-1 antitrypsin deficiency and spontaneous pneumothorax: possible causal relationship. Pneumologia. 2014; 63(1):32-5 (ISSN: 2067-2993)
8. Campos MA, Lascano J. a1 Antitrypsin deficiency: current best practice in testing and augmentation therapy.Ther Adv Respir Dis. Jul 9 2014
9. Carey EJ, Iyer VN, Nelson DR, Nguyen JH, Krowka MJ. Outcomes for recipients of liver transplantation for alpha-1-antitrypsin deficiency–related cirrhosis. Liver Transpl. 2013; 19(12):1370-6 (ISSN: 1527-6473)
10. Köhnlein T, Janciauskiene S, Welte T. Diagnostic delay and clinical modifiers in alpha-1 antitrypsin deficiency. Ther Adv Respir Dis. 2010; 4(5):279-87 (ISSN: 1753-4666)