Biotinidase deficiency is a genetic, metabolic condition where the body is unable to recycle and reuse a vitamin called biotin (also known as vitamin B7 or vitamin H) due to genetic changes in the BTD gene. Biotin is important for breaking down and converting carbohydrates, fats and proteins to energy.

These genetic changes in the BTD gene causes a protein called biotinidase to not work properly. Biotinidase is involved in recycling biotin and when biotinidase does not work properly, there is not enough biotin for important metabolic processes in the body. This leads to symptoms such as delayed development, weak muscle tone (hypotonia), seizures, hair loss, as well as issues with the skin, eyes, hearing and others. There are two forms of biotinidase deficiency:

• profound biotinidase deficiency – severe form of the condition with symptoms presenting early in life; this condition can be life-limiting without treatment
• partial biotinidase deficiency – mild symptoms that usually presents during time of stress or illness

Early detection and management of biotinidase deficiency is important to prevent permanent damage. In Australia, biotinidase deficiency is usually diagnosed after symptoms develop. Biotinidase deficiency is in the process of being added to Australia’s newborn bloodspot screening (NBS) programs. For more information, please visit the Australian Government Department of Health, Disability and Ageing: What is screened in the program page. Children with biotinidase deficiency who are diagnosed early and treated before symptoms develop can remain healthy and have normal development. Management of biotinidase deficiency involves supplementation of oral biotin in the free, non-protein bound form. Treatment of biotinidase is life-long.

Synonyms: BTD deficiency; deficiency of biotinidase; juvenile-onset multiple carboxylase deficiency; late-onset multiple carboxylase deficiency

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:79241 Biotinidase deficiency

ICD11: 5C50.E0 Classical organic aciduria

Symptoms of biotinidase deficiency can vary between individuals and present at different times. Those with profound biotinidase deficiency will have more severe symptoms than those with partial biotinidase deficiency. Children with profound biotinidase deficiency may develop symptoms within weeks after birth, or later in childhood, often within the first ten years of life. Individuals with partial biotinidase deficiency, on the other hand, may only develop symptoms when their body is under stress, such as illness.

If a child with biotinidase deficiency is diagnosed early and treated before symptoms appear, the child can grow and develop in a similar way to their healthy peers who don’t have biotinidase deficiency. However, if not diagnosed and treated early, the child may have:

• delayed development
• weak muscle tone (hypotonia)
• seizures
• hair loss (alopecia)
• skin issue, such as rashes
• issues with vision
• hearing loss
• fungal infections

Whilst many of these symptoms are reversible with early detection and treatment, symptoms such as vision, hearing loss and developmental delay may not be completely reversed if they occur before treatment. Children with profound biotinidase deficiency can also develop metabolic acidosis (where the blood becomes too acidic); if left untreated, this can lead to coma and death.

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.

Biotinidase deficiency is a genetic condition. It is caused by disease-causing genetic changes (variants) in the BTD gene located on Chromosome 3.

All individuals have two copies (alleles) of the BTD gene – one on each chromosome that is inherited from each parent. Biotinidase deficiency is an autosomal recessive condition, which means both copies of the BTD 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

In Australia, biotinidase deficiency is usually diagnosed after symptoms develop and may include a blood test (to test for biotinidase activity in the blood) and genetic testing.

Biotinidase deficiency is in the process of being added to Australia’s newborn bloodspot screening (NBS) programs. For more information, please visit the Australian Government Department of Health, Disability and Ageing: What is screened in the program page.

A timely diagnosis is critical for better patient outcomes, the provision of the best possible care and treatment options, access to services and support, increased reproductive confidence and the ability to participate in clinical trials.

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.

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.

Healthcare professionals involved in the clinical care of individuals with biotinidase deficiency may include paediatricians, metabolic doctors, nurses, neurologists, dieticians, and others. The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

We are not aware of any clinical care guidelines for GAMT deficiency in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

The following recommendations is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

• Laboratory diagnosis of biotinidase deficiency, 2017 update: a technical standard and guideline of the American College of Medical Genetics and Genomics

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.

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.

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 any clinical trials with your medical team to determine suitability and eligibility.

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

We are not aware of any rare disease organisations specifically for biotinidase deficiency 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.

Biotinidase deficiency 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, including families and carers, 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 people 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 biotinidase deficiency can be found at:

• Genetic and Rare Diseases (GARD) Information Center: Biotinidase deficiency
• National Organization for Rare Disorders (NORD): Biotinidase deficiency

Orphanet: Biotinidase deficiency

GeneReviews^®: Biotinidase Deficiency

Online Mendelian Inheritance in Man, OMIM^®: #253260 Biotinidase deficiency

Biotinidase deficiency: A treatable neurometabolic disorder

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.