Tyrosinaemia type II is a genetic, metabolic condition in which the body is unable to properly break down tyrosine due to genetic changes (variants) in the TAT gene.^1-3 Tyrosine is an amino acid that is a building block for many proteins.⁴ The TAT gene produces an enzyme called tyrosine aminotransferase (TAT). which is involved in breaking down tyrosine. The breakdown of tyrosine is a multistep process, and TAT is responsible for the first step, which converts tyrosine to p‑hydroxyphenylpyruvate.¹ In tyrosinaemia type II, there is low or no TAT activity, resulting in a build up of tyrosine, affecting the eyes and skin, and in some cases, the central nervous system.

In Australia, tyrosinaemia type II is often detected shortly after birth via newborn bloodspot screening (NBS) programs. Additional testing is required to confirm the diagnosis. Early diagnosis and treatment of tyrosinaemia type II can prevent development of symptoms or reduce severity, leading to only mild symptoms.²

There are also two other types of tyrosinaemia (tyrosinaemia type I and tyrosinaemia type III) that are caused by genetic changes in other genes and are currently being detected via Australia’s newborn bloodspot screening (NBS) programs.

Synonyms: Keratosis palmoplantaris-corneal dystrophy syndrome; Oculocutaneous tyrosinemia; Richner-Hanhart syndrome; Tyrosinemia due to TAT deficiency; Tyrosinemia due to tyrosine aminotransferase deficiency; Tyrosinemia type II ^2,5

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:28378 Tyrosinemia type 2

ICD-11: 5C50.12 Tyrosinaemia type 2

Tyrosinaemia type II typically affects the eyes, skin and in some cases, the central nervous system. If untreated, characteristic symptoms of tyrosinaemia type II include:^1-6

• inflammation of the cornea (front layer of the eye) – this inflammation is also known as keratitis, and be accompanied by pain, light sensitivity (photophobia), and impaired eyesight; symptoms often develop in the first year of life
• skin lesions, such as painful palmoplantar hyperkeratosis (thickening of the skin on the palms of hands and soles of feet that is very painful); symptoms often develop after the first year of life or with symptoms of the eye
• intellectual disability ranging from mild to severe, and in rare cases, developmental delay

Early diagnosis and treatment of tyrosinaemia type II can prevent development of symptoms or reduce severity, leading to only mild symptoms.²

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

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Tyrosinaemia type II is a genetic condition. It is caused by disease-causing genetic changes (variants) in the tyrosine aminotransferase (TAT) gene located on Chromosome 16.^1,2

All individuals have two copies (alleles) of the TAT gene – one on each chromosome that is inherited from each parent. Tyrosinaemia type II is an autosomal recessive condition,^1-2 which means both copies of the TAT gene must have the disease-causing genetic variants. More information on autosomal recessive inheritance pattern can be found at Centre for Genetics Education: Autosomal recessive inheritance.

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 about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Newborn screening

In Australia, tyrosinaemia type II is usually detected via the newborn bloodspot screening (NBS) programs.  Shortly after birth and with parental consent, a nurse or midwife will collect the baby’s blood via a heel prick blood test. The healthcare provider will then send it to a specific laboratory to test for a range of rare conditions, including tyrosinaemia type II. If the test results suggest that there is a risk of the baby having one of screened conditions, laboratory staff will promptly get in touch with healthcare providers. The healthcare providers will then arrange for the baby to have further testing to confirm if the baby actually has the condition. The healthcare providers will also organise for the baby to receive urgent care if required. Depending on your state or territory, parents may or may not receive a notification if the test results are clear. You can find out more about NBS in your state or territory at Australian Government Department of Health, Disability and Ageing: Delivering newborn bloodspot screening programs.

Newborn bloodspot screening is a reliable way to check for certain rare conditions early in life. Although it’s extremely rare, cases can sometimes be missed. If you are concerned your baby may have a condition that they have already been screened for, you should contact a medical professional.

Diagnosis

A diagnosis of tyrosinaemia type II may be suspected based on an abnormal result from NBS but additional tests or a clinical examination will be required to confirm a diagnosis. For individuals who are not screened at birth or if undetected during NBS screening, tyrosinaemia type II is often diagnosed after symptoms develop.

Diagnosis of tyrosinaemia type II may be made based on clinical evaluation of symptoms, laboratory tests on blood and urine samples to detect for increased levels of tyrosine and other tyrosine metabolites, and confirmed by genetic testing.⁵

As part of the diagnostic process, doctors may do a differential diagnosis, which is to rule out other conditions that have similar symptoms, such as tyrosinaemia type I, tyrosinaemia type III, and palmoplantar keratoderma with periorificial keratotic plaques.^2,5

Please speak to your medical team to learn more about the available pathways for diagnosis of this condition.

There is no curative treatment for tyrosinaemia type II. Treatment is life-long and consist of a low-protein diet (to restrict intake of tyrosine and phenylalanine), together with a specialised nutritional supplement.⁴ The ASIEM Low Protein Handbook for Tyrosinaemia has more information about the special diet.

If tyrosinaemia type II is diagnosed and treated early enough, treatment may prevent the development of eye and skin symptoms and can also prevent intellectual disability.² For those who have developed symptoms before diagnosis, treatment with the low protein diet can quickly lead to improvement of the skin and eye lesions, even within days or weeks.¹

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities. For many rare diseases, treatment options may be limited. Participation in a clinical trial may provide access to new or emerging therapies.

Healthcare professionals involved in the care of individuals living with tyrosinaemia type II may include general practitioners (GP), paediatricians, metabolic physicians, metabolic nurses, genetic counsellors, and other metabolic specialists and care team. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

This may not be applicable to all rare diseases but for many, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

If you know of any relevant emergency management guidelines or information relevant to emergency care, please let us know via the  Contribute page.

Metabolic Dietary Disorders Association (MDDA): Latest Research Updates has information about key areas of ongoing research for various inborn errors of metabolism conditions, including amino acid disorders.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

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

Australian Organisation:

Metabolic Dietary Disorders Association (MDDA)
Website: https://mdda.org.au/

Metabolic Dietary Disorders Association Inc (MDDA) is the national peak consumer body dedicated to supporting, educating, connecting, and representing all individuals their families and carers living with Inborn Errors of protein Metabolism (IEpM).

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

Tyrosinaemia type II varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

• The ASIEM Low Protein Handbook for Tyrosinaemia

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on tyrosinaemia type II can be found at:

• The ASIEM Low Protein Handbook for Tyrosinaemia
• Genetic and Rare Diseases (GARD) Information Center: Tyrosinemia type ii
• National Organization for Rare Disorders: tyrosinemia type II

Orphanet: Tyrosinemia type 2

GeneReviews^®: Tyrosinemia Type II 

Online Mendelian Inheritance in Man, OMIM^®: #276600 – Tyrosinemia, Type II; TYRSN2

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team.

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.