Zellweger Syndrome

Zellweger Syndrome Disease

Zellweger syndrome is a rare, inherited genetic disorder present at birth that affects the body’s ability to form functional peroxisomes, which are tiny cell structures needed to break down fats and toxins. It is the most severe type of the Zellweger spectrum disorders.

Symptoms and Causes

What are the symptoms of Zellweger syndrome?

Symptoms usually appear soon after birth and affect multiple organs:

Vision and hearing loss.
Distinctive facial features.
Weak muscle tone (hypotonia).
Seizures.
Enlarged liver (hepatomegaly).
Jaundice.
Kidney abnormalities.

What causes Zellweger syndrome?

Zellweger syndrome is caused by inherited genetic mutations that prevent the normal formation and function of peroxisomes, essential cell structures for breaking down fats and toxins.

Mutations in PEX genes: This condition occurs when there are mutations in one of the PEX genes (such as PEX1, PEX2, PEX3, PEX5, PEX6, etc.), which encode peroxins needed to build and maintain peroxisomes. Without these proteins, peroxisomes cannot form or work properly. Mutations in PEX1 are the most common cause.
Autosomal recessive inheritance: Zellweger syndrome follows an autosomal recessive pattern, meaning a child must inherit two mutated gene copies (one from each parent) to develop the disease, while carriers (with one copy) typically have no symptoms.
Defective peroxisome biogenesis: Because these gene mutations disrupt peroxisome biogenesis, cells lack functional peroxisomes needed for metabolizing very long‑chain fatty acids and detoxifying harmful compounds, leading to the accumulation of toxic substances.

Diagnosis of Zellweger Syndrome

A healthcare provider usually notices the facial features of ZS right after birth. The following tests confirm the diagnosis.

Clinical Evaluation (Physical Signs): Doctors initially suspect Zellweger syndrome based on characteristic features in newborns—such as distinctive facial appearance, poor muscle tone (hypotonia), feeding difficulties, and neurological signs like seizures.
Biochemical Tests (Blood & Urine): Blood and urine tests check for abnormally elevated very long-chain fatty acids (VLCFAs) and other metabolic markers that reflect peroxisomal dysfunction. These biochemical abnormalities support the diagnosis.
Imaging tests: Ultrasound and MRI assess internal organs (like the liver, kidneys, and brain) for characteristic abnormalities.
Genetic Testing (PEX Genes): The definitive diagnosis is confirmed with genetic testing that identifies pathogenic mutations in the PEX genes, which are responsible for peroxisome biogenesis. This also informs family counseling and future prenatal testing.

What are the Zellweger syndrome risk factors?

Zellweger syndrome is a rare, inherited genetic disorder that occurs when a child inherits defective copies of certain genes from both parents.

Autosomal recessive inheritance: A child must receive a mutated gene from both parents to develop the condition
Gene mutations: Mutations in any of several PEX genes (most often PEX1) disrupt peroxisome formation, leading to the disorder.
Carrier parents: Each pregnancy has a 25% chance of the child being affected if both parents are carriers.

What treatment options are available for Zellweger syndrome?

There is no cure for Zellweger syndrome; treatment focuses on supportive care to manage symptoms and improve quality of life.

Supportive Symptom Management: Care involves a multidisciplinary team to address feeding, muscle weakness, seizures, and organ dysfunction. This includes physical support, palliative care, and routine monitoring.

Seizure & Symptom Medications: Antiepileptic drugs control seizures, and hormone/vitamin supplements (like vitamins A, D, E, and K) help correct deficiencies caused by metabolic abnormalities.

Sensory Aids & Surgeries: Hearing aids/implants and vision support (glasses or cataract surgery) are used to manage sensory impairments.

Bile Acid Therapy (Cholic Acid): Cholic acid (FDA-approved therapy) may improve liver function and reduce toxic bile acid buildup in patients with peroxisomal dysfunction, though benefits vary and neurologic symptoms may persist.

Experimental & Future Approaches: Research in gene therapy, stem cell therapy, and enzyme precursors is ongoing but not yet standard or proven treatments.