Peroxisomal Disorders (Zellweger Syndrome Spectrum)

Peroxisomal disorders are rare genetic conditions that affect how your body breaks down fats and builds important molecules. Peroxisomes are tiny structures inside your cells that do hundreds of essential jobs. They help your body process very long chain fatty acids, create certain types of fats needed for your brain, and remove toxic substances.

Zellweger syndrome spectrum describes a group of peroxisomal disorders that range from severe to milder forms. The most severe form is classic Zellweger syndrome, which affects multiple organs from birth. Milder forms include neonatal adrenoleukodystrophy and infantile Refsum disease. All forms are caused by mutations in genes that build and maintain peroxisomes.

When peroxisomes do not work properly, harmful fats build up in your body and brain. Your body also cannot make enough DHA, an omega-3 fatty acid critical for brain and eye development. These disorders are inherited in an autosomal recessive pattern, meaning both parents must carry the gene mutation for a child to be affected.

• Poor muscle tone and weakness in infants
• Feeding difficulties and failure to gain weight
• Distinctive facial features including high forehead and broad nasal bridge
• Seizures that may begin in infancy
• Vision problems or blindness
• Hearing loss
• Liver enlargement and dysfunction
• Developmental delays or loss of developmental milestones
• Brain abnormalities visible on imaging
• Kidney cysts or other organ malformations

Symptoms typically appear in the first months of life for severe forms. Milder forms may not show symptoms until later in childhood. The severity and combination of symptoms varies widely across the spectrum.

Peroxisomal disorders are caused by mutations in genes that control peroxisome formation and function. Over 13 different genes can cause Zellweger syndrome spectrum disorders. These genes provide instructions for making proteins called peroxins, which are needed to build working peroxisomes. When these genes are mutated, peroxisomes either do not form at all or cannot do their jobs properly.

These conditions follow an autosomal recessive inheritance pattern. Both parents must carry one copy of the mutated gene for their child to be affected. Carrier parents typically have no symptoms themselves. There are no lifestyle or environmental risk factors that cause these genetic mutations, though certain populations may have higher carrier rates for specific mutations.

Peroxisomal disorders are diagnosed through a combination of clinical evaluation, blood tests, and genetic testing. Blood tests measure very long chain fatty acids, which are elevated in these conditions. DHA levels are typically very low because peroxisomes are needed to make this important omega-3 fatty acid. Other blood markers include phytanic acid and plasmalogen levels.

Rite Aid offers DHA testing as an add-on to our blood test panel. Low DHA levels can be an important early clue in diagnosing peroxisomal disorders. If results suggest a peroxisomal disorder, your doctor will order additional specialized testing including genetic analysis to confirm the diagnosis and identify the specific gene mutation involved.

• DHA supplementation to address deficiency and support brain development
• Specialized formulas and feeding support for infants with feeding difficulties
• Physical therapy to help with muscle tone and motor skills
• Occupational therapy to support daily functioning
• Medications to control seizures
• Hearing aids or cochlear implants for hearing loss
• Vision aids and support services for visual impairment
• Liver support and monitoring for liver dysfunction
• Nutritional support tailored to individual needs
• Regular monitoring by a team of specialists including geneticists, neurologists, and other experts