Alpha-1 Antitrypsin Deficiency (A1AD)

Metabolic Disorders Inborn errors of metabolism

IMPORTANT INFORMATION

The information on the Rare Awareness Rare Education (RARE) Portal is intended for educational purposes only and does not replace professional advice.

Rare diseases typically display a high level of symptom complexity and variability. Individuals diagnosed with the same rare disease may be impacted differently and each person’s experience is unique. Please seek support from qualified healthcare professionals to learn more about the most suitable care and support options for you.

For more information on this disease, please refer to RVA Partner, Alpha-1 Organisation Australia Inc.¹

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.

Contributors

This page has been co-developed with RVA Partner, Alpha-1 Organisation Australia Inc.¹

Emergency Management

There may be special considerations for the emergency management of individuals living with A1AD presenting to emergency departments.

Clinical Care Guidelines

Clinical Care Guidelines for A1AD are yet to be developed in Australia.

There is a clinical practice guideline available in the United States – The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult.

In Australia, there is a position statement (from the Thoracic Society of Australia and New Zealand) available to provide information to clinicians on the diagnosis and treatment of A1AD (please note, this does not represent a guideline).

Synonyms

A1AD, A1AD, A1AT Deficiency; AAT Deficiency; Alpha 1 Antitrypsin Deficiency, Alpha 1-proteinase Inhibitor Deficiency; ORPHA:60

Summary

Alpha-1 Antitrypsin Deficiency (A1AD) is a genetic condition associated with increased risk of chronic obstructive pulmonary disease (COPD), liver disease, skin conditions and inflammation of the blood vessels.^1,2 Lung problems are common in adults with A1AD, whilst liver disease and skin conditions are observed in some adults and children.² Some people living with A1AD do not have any symptoms.

A1AD is caused by genetic changes (mutations) in the SERPINA1 gene.² These genetic changes can either cause too little or no functional alpha-1 antitrypsin protein (AAT), or abnormal forms of the protein, to be made. AAT is made in the liver and sent to the lungs through the bloodstream to protect the lungs from damage.² Having no or low levels of AAT tends to cause more damage in the lungs whilst a build-up of abnormal AAT is more likely to affect the liver.²^,3

Useful Links for Professionals

GeneReviews®: Alpha-1 Antitrypsin Deficiency

Online Mendelian Inheritance in Man (OMIM): #613490 Alpha-1 Antitrypsin Deficiency (A1ATD)

Orphanet: Alpha 1 Antitrypsin Deficiency

Human Phenotype Ontology (HPO): Alpha-1 Anti-trypsin Deficiency

Royal College of Pathologists of Australasia (RCPA): Pathology Test – Alpha-1-antitrypsin

Symptoms

Alpha-1 It Starts with the Liver. © Depiction of a deliberately anatomically incorrect liver to emphasis the role of the liver in genetic COPD By Gaynor Heading 2022. People with A1AD are predisposed to lung (pulmonary) disease (including emphysema, bronchitis, bronchiectasis and COPD) and liver disease (hepatitis, fibrosis, cirrhosis, hepatocellular carcinoma and liver failure).³ They may also be affected by issues associated with skin (panniculitis) and blood vessels (vasculitis). Symptoms may include shortness of breath and wheezing, repeated infections of the lungs and liver, jaundice, fatigue, rapid heartbeat when standing, vision problems and weight loss.²It is recommended that A1AD testing should be considered for individuals with chronic airflow obstruction, adult-onset asthma, and bronchiectasis, particularly those under 40—45 years who are non-smokers or also have liver or skin disease.^4,5

Children with A1AD can be born with liver damage or develop chronic liver disease during childhood.¹^,6 Symptoms and complications can include jaundice, insufficient weight gain, weight loss, enlarged liver (hepatosplenomegaly), enlarged spleen (splenomegaly), reduced or blocked flow of bile from the liver (cholestasis) and neonatal and chronic hepatitis.¹^,6

Please speak to your medical team to learn more about the symptoms and complications of A1AD.

Cause/Inheritance

A1AD is caused by inheritable genetic variations in the SERPINA1 gene that produces the AAT protein.² Every individual has two SERPINA1 gene alleles (one from each parent), with the normal, non-disease-causing allele referred to as the “M” allele.⁷ There have been reports of over 150 different genetic variations in SERPINA1 that can result in either abnormal or no AAT protein being produced, with the most common being the “S” and “Z” alleles.⁷ Each individual can be either homozygous (have two of the same SERPINA1 alleles; e.g. “MM”, SS”, “ZZ”) or heterozygous (have two different alleles; e.g. “SZ”, “MZ”, “MS”). For people with A1AD, the risk and severity of their condition is influenced by the type and combination of their SERPINA1 alleles.¹^,3

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information on genetic counselling can be found on the National Services page and specific State and Territory Services pages on the RARE Portal.

Diagnosis

Diagnosis of A1AD may be based on detection of low AAT levels in the blood and confirmed with genetic testing.

More information about AAT tests can be found at Pathology Tests Explained: Alpha-1-antitrypsin.⁵

Treatment

There is no overall curative treatment for A1AD, but clinical trials are underway.¹ Meanwhile, there are management strategies for the symptoms and diseases associated with A1AD. It is best to speak with your medical team to learn more about possible management strategies which may reduce the risks or slow progression of disease. It is also recommended that individuals with A1AD avoid exposure to cigarette smoke, dust and fumes and reduce their alcohol intake due to the associated risk of lung and liver diseases.³

For some individuals, augmentation therapy (intravenous infusions of AAT concentrate) may be used to increase AAT levels in the blood and lungs to treat A1AD-associated lung diseases.⁴ Augmentation therapy is approved for use in Australia by the Therapeutic Goods Administration (TGA) specifically for individuals with a A1AD diagnosis, confirmed low levels of AAT and clinical evidence of emphysema; however, augmentation therapy is currently not subsidised by Medicare and can be costly.

Clinical Care

According to the International Classification of Diseases 11th Revision (ICD11), A1AD is classified as a metabolic condition. In Australia, the healthcare professionals involved in the treatment of A1AD generally include general practitioners (GP), geneticists, pulmonologists, hepatologists and nephrologists.¹ The need for different healthcare professionals may change over a person’s lifetime and may extend beyond those listed here.

Research

Please visit Australian Clinical Trials to learn about clinical trials for A1AD in Australia; there may not be any clinical trials currently available.

Information regarding clinical trials for A1AD in other countries can be found at ClinicalTrials.gov; there may not be any clinical trials currently available.

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Rare Disease Organisation(s)

Alpha-1 Organisation Australia Inc RVA Partner Australian Organisation
Website: https://www.a1oa.org.au/
Contact form: https://www.a1oa.org.au/contact/

Alpha-1 Organisation Australia Inc. is a charity that provides support and advocacy for Alpha-1 Australians as well as promotes educational research aimed at advancing breakthroughs and ultimately finding a cure.

ALPHA-1 Association of Australia (AAA) Australian Organisation
Website: https://www.alpha1.org.au/
Phone: (07) 3103 3363, 0410 108 104
Email: [email protected]

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance.

Please see the National and State Services pages.

Mental Health

Please see the ‘Mental Health’ sections listed on the National and State Services pages.

Other

Further information on A1AD can be found at:

For more general information on lung, liver and kidney health, please visit:

References

Alpha-1 Organisation Australia Inc. Accessed 12 May 2022. Available from: https://www.a1oa.org.au/
Genetic and Rare Diseases (GARD) Information Center. Aromatic L-amino acid decarboxylase deficiency. Accessed 12 May 2022. https://rarediseases.info.nih.gov/diseases/770/aromatic-l-amino-acid-decarboxylase-deficiency
Greene CM, Marciniak SJ, Teckman J, Ferraroti I, Brantly ML, Lomas DA et al. α1‑Antitrypsin deficiency. Nat. Rev. Dis. Primers. 2016;2:16051. Available from: https://www.nature.com/articles/nrdp201651
Dummer J, Dobler CC, Holmes M, Chambers D, Yang IA, Parkin, L et al. Diagnosis and treatment of lung disease associated with alpha one‐antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand*. Respirology. 2020; 25:321-335. Available from: https://doi.org/10.1111/resp.13774
Pathology Tests Explained. Alpha-1-antitrypsin. Accessed May 23, 2022. https://pathologytestsexplained.org.au/learning/test-index/alpha1-antitrypsin
Comba A, Demirbaş F, Çaltepe G, Eren E, Kalayci A. Retrospective analysis of children with α-1 antitrypsin deficiency. Eur. J. Gastroenterol. Hepatol. 2018; 30(7):774-778. Available from: https://doi.org/10.1097/MEG.0000000000001108
Sandhaus RA, Turino G, Brantly ML, Campos M, Cross CE, Goodman K et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obst. Pulm. Dis. 2016; 3(3):668-682. Available from: http://doi.org/10.15326/jcopdf.3.3.2015.0182

Page Last Updated

13/11/2023 16:43

Metabolic Disorders Inborn errors of metabolism