Peroxisome Biogenesis Disorder (PBD)
Otherwise known as Zellweger Spectrum Disorders (ZSD), comprised of Infantile Refsum’s Disease, Neonatal Adrenoleukodystrophy and Zellweger Syndrome
Inheritance:
Autosomal recessive
Inheritance from both parents will result in the disease
Age range at onset:
Newborn to early childhood
Specialists you may see:
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.
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.