Description of the condition

Peroxisome Biogenesis Disorders (PBD) are a group of rare genetic disorders that affect peroxisome function in cells. These disorders result from mutations in various genes involved in peroxisome creation and function. PBDs encompass a range of conditions, causing developmental delays, vision and hearing impairments, and organ dysfunction. Treatment primarily focuses on managing symptoms and providing supportive care to enhance the individual’s quality of life.

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Cause

Caused by mutations in one of 13 PEX genes, with PEX1 mutations the most common. These genes contribute to the creation and functioning of peroxisomes, which are vital to breakdown fatty acids and produce fats needed by the nervous and digestive systems. Peroxisomes also contribute to development and functioning of the brain. In NALD and Infantile Refsum’s Disease, mutations allow some peroxisomes to form.

Inheritance

Autosomal recessive: In autosomal recessive conditions, two copies of the genetic mutation are needed to cause the condition. We all have two copies of every gene, one from our mother and one from our father. The parents of someone with an autosomal recessive condition both carry one copy of the gene with a genetic mutation. Therefore, someone with an autosomal recessive condition has two copies of the genetic mutation, one copy from each parent. Each child of parents that both carry the genetic mutation will have a 25% chance of having the condition, a 50% chance of carrying the genetic mutation (like the parent), and a 25% chance of not having the condition.

This image shows the inheritance of genes from parents to their children and the resulting combination of genes the child will have. Red represents the genetic mutation, blue represents the normal copy of the gene. The line from each parent shows which gene they pass on to their child. The colours of the individuals tell the effect of the genes they have, red means they will be at risk of being affected, blue means they will not be at risk of being affected, and yellow means they carry the mutated gene.

Genetic counselling

Genetic counselling is essential for affected families due to the inheritance pattern of the condition. This is available at hospitals and Regional Genetic Centres. Please contact your doctor if you have any questions.

Learn more about genetic testing and counselling here.

Symptoms

Peroxisome Biogenesis Disorders can be broken down into three conditions of increasing severity: Infantile Refsum’s Disease, Neonatal Adrenoleukodystrophy and Zellweger Syndrome.

Newborns with Zellweger syndrome suffer from hypotonia, problems with hearing, vision and feeding, and seizures as well as developmental delay. These infants may have hepatomegaly and coagulopathy. The condition has a life-threatening effect on a child’s liver, heart and kidneys,  as well as causing bone abnormalities such as bone spots and large fontanelles. Distinctive facial features of newborns with Zellweger syndrome are a broad nasal bridge, flattened face and high forehead. Life expectancy is less than one year.

Neonatal adrenoleukodystrophy is characterised by seizures, hypotonia, progressive vision and hearing loss, mild facial abnormalities such as hypertelorism and a flat midface, and developmental delay. Older children with the condition may present with adrenal insufficiency,  and those who are less mobile are at risk of osteoporosis and fractures. Over time, those with NALD lose previously acquired skills, develop dementia and ultimately die, with only a few surviving into teenage years.

Infantile Refsum’s disease symptoms are similar to that of Zellweger syndrome, but will progress more slowly. Those with Infantile Refsum’s Disease may survive into adulthood. Some at the mildest end of the spectrum experience some developmental delay in childhood and some vision or hearing difficulties in adulthood and may have no further symptoms.

More symptom information

Learn more about specific symptoms of this leukodystrophy in these pages.

Treatments

Although there is currently no specific treatment for this leukodystrophy, there is condition management information that may be useful for you in managing your or your loved one’s leukodystrophy.

Current research

There may be a current clinical trial, natural history study or patient registry for your condition. Check our current research page and ask your specialist doctor for more information.

Scientific research

We understand that research is a significant priority and source of hope for the leukodystrophy community. There is more research in leukodystrophy now than ever before. Alex TLC actively promotes and supports research in a number of ways.

Every month we update our database of research summaries with the most recent research. This includes summaries of leukodystrophy articles, clinical trials and pharmaceutical press releases. Our summaries allow our community to read about relevant recent research developments in a format that is easily understood.

How we can support you

Learn about the ways in which we can help in the how we support you section. When you or a family member been diagnosed with a leukodystrophy it may be difficult to know where to go for more advice – this information could help.

How we support you

Services and equipment

Our services and equipment section is here to help leukodystrophy patients and their families manage their condition. All information is based on our knowledge of UK services, however, our team are happy to receive support requests from other countries – email us.

Services and equipment

Healthcare professionals

You may be introduced to many different medical professionals which you may find confusing. View our guide to the health and care professionals you may encounter, with short descriptions about what they do.

Health and care professionals

Other resources

Links to useful information

We take great care in only selecting credible, useful links and resources, however we cannot be held responsible for the content of external websites or other sources.

View the full list of leukodystrophies