Zellweger Syndrome is one class of Cerebrohepatorenal syndromes. It is a rare hereditary disorder and caused by a gene mutation that affects the way peroxisomes function.

1. Zellweger Syndrome
“Cerebrohepatorenal Syndromes”
A rare hereditary disorder; tertiary
in the Zellweger Spectrum

2. Zellweger's or ZS is a Peroxisome biogenesis disorder meaning there is a
mutation in the amount of peroxisomes that will break down lipids, and
contribute to the production of Myelin. Most people with Zellweger’s have long
chains of fat in their blood.
Peroxisomes are cell structures that break down toxic substances and form
lipids (fatty acids. oils, and waxes) that are necessary for cell function.
Peroxisomes are required for normal brain development and function and the
formation of myelin, the whitish substance that coats nerve fibers.
They are also required for normal eye, liver, kidney, and bone functions.
What is Zellweger’s Syndrome?

3. What cause it?
If you are born to parents who both carry an autosomal recessive change (two
copies of an abnormal gene must be present in order for the disease or trait to
develop.), you have a 1 in 4 chance of getting the malfunctioning genes from
both parents and developing the disease, meaning you have a 50% (1 in 2)
chance of inheriting the abnormal gene. This would make you a carrier.
Zellweger syndrome is caused by mutations in any one of at least 12 genes;
mutations in the PEX1 gene are the most common cause, (70%). It is inherited
in an autosomal recessive manner.There is no cure for Zellweger syndrome;
treatment is generally symptomatic and to be supportive.

4. Who is it most common in?
ZS is most common in newborns, most that
have inherited ZS die before their first
birthday reaching no physical or mental
milestones that affects 1 in 50,000
individuals.

5. What part of the body does ZS affect?
ZS effects…
● Upper forehead
● Earlobes
● Skull
● Muscles
● Liver
● Digestive tract
● Sclera
● Bones
● Cochlearis
● Brain
● Larynx

6. What are the symptoms?
The symptoms of ZS are…
● Poor sucking
● Epileptic seizures
● Psychomotor retardation: slowed
physical and emotional response
● Impaired hearing
● Nystagmus: rapid involuntary eye
movement
● Hepatomegaly: enlarged liver
● High forehead
● Flat occiput: bone in back of skull
● Large fontanelle: soft spot
● Abnormal Moro response: abnormal
reflex when startled
● Low broad nasal bridge
● Epicanthus: skin fold of the eyelids
● High arched platelet: roof of mouth
● External ear deformities
● Micrognathia: small chin
● Multiple skin folds of the neck
● Brushfield spots: Speckled iris
● Cataracts: Cloudy corneas
● Glaucoma: high fluid pressure in the
eyes causing blindness
● Retinal pigmentation
● Severe hypotonia: too much muscle
tone
● Hyperreflexia: slow reflexes

7. When are the onset of symptoms?
Zellweger syndrome is a Congenital
disorder, meaning the symptoms are present
at birth. After the onset typically most
infants have up to 5 years to live.

8. What are the exams/tests?
An Integrated Genetics Inhertist would test for a PEX1
gene mutation test, which is present in 70% of people
with ZS. If you have 2 copies of the mutation you have
Zellweger’s, one copy you are a carrier of the disease.
Measurement of plasma very-long-chain fatty acid
(VLCFA) levels is the most commonly used and most
informative most times also.

9. What are the treatments?
Medical science as of now has not discovered a cure and
there are general treatments besides symptomatic and
supportive methods. Symptomatic therapy may include:
gastrostomy to provide acceptable calorie intake, hearing
aids, cataract removal in infancy, glasses, vitamin
supplementation, primary bile acid therapy, antiepileptic
drugs, and possibly monitoring for hyperoxaluria.
(removal of salt in urine)

10. What’s the history?
Zellweger Syndrome was discovered by an
Switz-American pediatrician Hans
Zellweger.

11. Bibliography
http://www.genome.gov/glossary.cfm?key=mutation
http://www.nlm.nih.gov/medlineplus/ency/article/002052.htm
http://ulf.org/the-zellweger-spectrum
https://www.labcorp.
com/wps/wcm/connect/intgeneticslib/IntegratedGenetics/Resources/Diseases
/Zellweger+Syndrome+Spectrum
http://www.disabled-world.com/disability/types/zellweger-syndrome.php
http://www.ncbi.nlm.nih.gov/books/NBK1448/