Zellweger Syndrome Health Article

Demographics

The frequency of this condition is estimated to be 1 in 50,000. There is no reported difference in the incidence in any particular sex or ethnic background.

Signs and symptoms

The characteristic facial features of Zellweger syndrome include:

• high forehead
• widely spaced eyes (hypertelorism)
• low, broad, or flat nasal bridge
• "full" cheeks
• small chin (micrognathia)
• forward tilting (anteverted) nostrils
• vertical fold of skin over the inner corner of the eye (epicanthal fold)
• upslanting eyes
• shallow orbital ridges
• minor ear abnormalities

Other characteristics include, but are not limited to:

• breech presentation at birth (feet first)
• extremely weak muscles (hypotonia)
• weak sucking and swallowing reflexes
• high arched palate
• absent deep tendon reflexes
• seizures
• deafness
• enlarged liver (hepatomegaly)
• enlarged spleen
• gastrointestinal bleeding
• slow growth after birth
• severe mental retardation
• abnormal brain findings
• involuntary, rhythmic movements of the eyes (nystagmus)
• large space between the bones of the skull (fontanel)
• flat back part of the head (occiput)
• tiny white or yellow spots on the colored part of the eyes (brushfield spots)
• redundant skin on neck
• congenital cloudy lenses of the eye (cataracts)
• possible heart defects
• a single crease across the palm of the hands (simian creases)
• fixed, immovable joints (contractures)
• misaligned bones in the front part of the foot/club foot (talipes equinovarus)
• undescended testicles (cryptorchidism)
• underdeveloped thymus (thymus hypoplasia)
• hearing impairment
• failure to thrive
• psychomotor retardation
• high levels of iron or copper in the blood

Diagnosis

Diagnosis is based on clinical characteristics combined with a series of tests to determine the peroxisomal function and structure. Biochemical abnormalities include elevated levels of very long chain fatty acids, a decrease in the levels of a peroxisomal enzyme dihydroxyacetone phosphate acyltransferase (DHAPAT), the presence of abnormal intermediates in bile acid formation, and a lack of plasmalogens in a blood sample. Absence of peroxisomes in liver biopsy specimen is considered essential for the diagnosis of Zellweger syndrome.

Prenatal diagnosis for Zellweger syndrome is possible through chorionic villus sampling (CVS) and amniocentesis. Diagnosis may be made by measuring the synthesis of plasmalogens in cultured CVS or amniotic fluid cells or by measuring the amount of very long chain fatty acids. Other tests may be useful, including measuring the amount of the peroxisomal enzyme DHAPAT in the amniotic fluid.

There are other leukodystrophies, including neonatal adrenoleukodystrophy, infantile Refsum disease, and hyperpipecolic acidemia. The milder diseases may be due to having partial peroxisome function.

Treatment and management

In general there is no cure and no treatment for Zellweger syndrome.

Prognosis

The prognosis for individuals who have Zellweger syndrome is poor. Those with the disease usually only live for a few months after birth. Rarely do individuals who have Zellweger syndrome live longer than one year.

BOOKS

Jones, Kenneth Lyons, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia: W.B. Saunders Company, 1997.

ORGANIZATIONS

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.

United Leukodystrophy Foundation. 2304 Highland Dr., Sycamore, IL 60178. (815) 895-3211 or (800) 728-5483. Fax: (815) 895-2432. <http://www.ulf.org>.

WEBSITES

"NINDS Zellweger Syndrome Information Page." National Institute of Neurological Disorders and Stroke. <http://www.ninds.nih.gov/health_and_medical/disorders/zellwege_doc.htm>.

Renee A. Laux, MS