Methylmalonic acidemia due to transcobalamin receptor defect is a genetic, metabolic condition and a type of organic acidemia. It is caused by genetic changes in the CD320 gene that is responsible for producing the transcobalamin receptor (TCBLR). The transcobalamin receptor helps cobalamin  (vitamin B12) to be taken up into cells. Genetic changes in the CD320 gene affects the function of the transcobalamin receptor, resulting in decreased cobalamin being taken up into cells and less cobalamin being available in cells. Once in the cells, the cobalamin is usually processed into a form that is involved in a multi-step process to break down certain amino acids (which are building blocks of protein) and some types of fats. With less cobalamin, this multi-step process is affected, leading to slight increase in methylmalonic acid that can be toxic to the body when at high levels. Whilst most people with methylmalonic acidemia due to transcobalamin receptor defect may not have any symptoms (are asymptomatic), in some cases it can cause slight increase in homocysteine levels and severe visual loss due to retinal vascular occlusive disease.

In Australia, methylmalonic acidemia due to transcobalamin receptor defect is often detected shortly after birth via newborn bloodspot screening (NBS) programs. For individuals who are not screened at birth, methylmalonic acidemia due to transcobalamin receptor defect is often diagnosed after symptoms develop.

Synonyms: Cd320 methylmalonic acidemia; MATR; Methylmalonic acidemia caused by mutation in cd320; Methylmalonic acidemia TCb1R type; Methylmalonic acidemia, TCb1R type; Methylmalonic acidemia, TCb1R type

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.

Orphanet: Methylmalonic aciduria due to transcobalamin receptor defect

There is no known ICD:11 classification.

Rare diseases typically display a high level of symptom complexity. There is often a wide range of symptoms and the symptoms may vary between individuals in terms of its presentation, severity, duration and impact.

Please speak to your medical team to learn more about the symptoms 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.

Methylmalonic acidemia due to transcobalamin receptor defect is a genetic condition. It is caused by disease-causing genetic changes (variants) in the CD320 gene on chromosome 19. The CD320 gene is responsible for producing the transcobalamin receptor (TCBLR).

All individuals have two copies (alleles) of the CD320 gene – one copy inherited from each parent. Methylmalonic acidemia due to transcobalamin receptor defect is an autosomal recessive condition, which means both copies of the CD320 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

Screening

In Australia, methylmalonic acidemia due to transcobalamin receptor defect 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 Methylmalonic acidemia due to transcobalamin receptor defect. 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 methylmalonic acidemia due to transcobalamin receptor defect 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, methylmalonic acidemia due to transcobalamin receptor defect is often diagnosed after symptoms develop.

Diagnosis of methylmalonic acidemia due to transcobalamin receptor defect may be made based on clinical evaluation of symptoms, laboratory tests on blood samples to detect for increased levels of methylmalonic acid and increased C3-acylcarnitine levels, and confirmed by genetic testing.

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

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.

Healthcare professionals involved in the clinical care of individuals with methylmalonic acidemia due to transcobalamin receptor defect may include general practitioners (GP), paediatricians, geneticists, metabolic physicians, genetic counsellors, ophthalmologist and haemotologists. 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.

For many rare diseases, 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

If you know of any relevant clinical care guidelines, please let us know via the  Contribute page.

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.

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.

We are not aware of any rare disease organisations specifically for methylmalonic acidemia due to transcobalamin receptor defect in Australia. If you are aware of any relevant Australian organisations, please let us know via the Contribute page.

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.

Methylmalonic acidemia due to transcobalamin receptor defect 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.

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 relevant to methylmalonic acidemia due to transcobalamin receptor defect can be found at:

• Genetic and Rare Diseases (GARD) Information Center: Methylmalonic acidemia due to transcobalamin receptor defect

Orphanet: Methylmalonic aciduria due to transcobalamin receptor defect

Online Mendelian Inheritance in Man, OMIM^®: #613646 – Methylmalonic aciduria, Transient, due to transcobalamin receptor defect; MATR

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team. If you would like to see more information added to this page, please reach out via the Contact form. If you would like to share relevant resources for this condition, please visit the Contribute page.

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.