Zellweger syndrome (ZS) is a rare, hereditary disorder affecting infants and usually resulting in death.
Unusual problems in prenatal development, an enlarged liver, high level of iron and
copper in the blood and vision disturbances are among the major manifestations of
ZS. Mutations in the PEX1 gene cause ZS. ZS belongs to the Zellweger spectrum of peroxisome
biogenesis disorders (PDB, ZSS) and is considered the most severe of the PBDs. Infants
with ZS also lack muscle tone. Sometimes to the point of being unable to move, and
may not be able to suck or swallow. Some babies will be born with glaucoma retinal
degeneration and impaired hearing. Jaundice and gastrointestinal bleeding may also
occur. Symptoms include: characteristic facial appearance, seizures, inability to
feed, liver cysts with hepatic (liver) dysfunction, and chondrodysplasia punctata.
The most prominent dysmorphic (abnormal) features include a high forehead, hypoplastic
supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanel. The
head circumference is normal to large. Eye abnormalities include cataracts, glaucoma,
corneal clouding, Brushfield spots (gray or pale yellow spots that go around the sides
of the iris) optic nerve hypoplasia, and pigmentary retinal degeneration. There are
abnormalities in neuronal migration, some of which appear to be unique to this disorder
and which may be seen on an MRI of the head. Enlargement of the liver (hepatomegaly)
is present in 75 % of the cases; with periportal fibrosis resulting in jaundice, micronodular
cirrhosis, and hypoprothrombinemia. Renal cortical cysts are almost universally present
pathologically but may be missed on ultrasound study. Skeletal abnormalities include
clubbed feet, thumb rotation, and stippled chondral calcification of the patella and
acetabulum. Infants with this condition are significantly impaired and usually die
during the first year of life, usually having made no developmental progress.
TESTING, PHYSICAL FINDINGS, AND ICD-9-CM CODING
Biochemical abnormalities that are found in the blood and/or urine should be confirmed
in cultured fibro blasts. The tests are used to detect accumulation of very long chain
fatty acids (VLCFA) levels. Bony stippling (chondrodysplasia punctata) may be present
on radiological studies and this is suggestive of ZS in the proper clinical setting.
MRI of the brain may identify hypomyelination, cortical gyral abnormalities, and germinolytic
cysts that are highly suggestive of ZS. Molecular genetic testing for mutations in
the PEX genes.
ONSET AND PROGRESSION
The prognosis for infants with ZS is poor. Most infants do not survive past the first
6 months, and usually death is the result of respiratory failure, gastrointestinal
bleeding, or liver failure.
There is no cure for ZS, nor is there a standard course of treatment. Since the metabolic
and neurological abnormalities that cause the symptoms of Zellweger syndrome are present
during fetal development, treatments to correct these abnormalities after birth will
be limited. Most treatments are symptomatic and supportive and may include: gastrostomy
to provide adequate calories, hearing aids, cataract removal in infancy, glasses,
vitamin supplements, primary bile acid therapy, anti-epileptic drugs and possibly
monitoring for hyperoaluria, monitoring for coagulation factors and tests of liver
function. Avoidance of cow’s milk products is recommended to reduce exposure to phytanic
Suggested MER for Evaluation: If available in the MER, Plasma VLCFA abnormalities as outlined above or mutations in the PEX genes confirm
a diagnosis of one of the PBD’s. If such testing is not available, then a complete
review of the clinical history, course, and laboratory studies on which the diagnosis
is suspected will be needed for review. To then differentiate the three PBDs and to
evaluate the severity of the specific case, a complete physical and neurological examination