Zellweger Syndrome Causes, Symptoms, Diagnosis, Treatment

Zellweger Syndrome Causes, Symptoms, Diagnosis, Treatment

What is Zellweger Syndrome?

Zellweger syndrome is one of a group of four related diseases called peroxisome biogenesis disorders (PBD). The diseases are caused by defects in any one of 13 genes, termed PEX genes, required for the normal formation and function of peroxisomes. The PBDs are divided into two groups: Zellweger spectrum disorders and Rhizomelic Chondrodysplasia Punctua spectrum. The Zellweger spectrum is comprised of three disorders that have considerable overlap of features. These include Zellweger syndrome (ZS, the most severe form), neonatal adrenoleukodystrophy (NALD), and Infantile Refsum disease (IRD, the least severe form).

Peroxisomes are cell structures that break down toxic substances and synthesize 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. Zellweger spectrum disorders result from dysfunctional lipid metabolism, including the over-accumulation of very long-chain fatty acids and phytanic acid, and defects of bile acids and plasmalogens--specialized lipids found in cell membranes and myelin sheaths of nerve fibers. Symptoms of these disorders include an enlarged liver; characteristic facial features such as a high forehead, underdeveloped eyebrow ridges, and wide-set eyes; and neurological abnormalities such as mental retardation and seizures. Infants will Zellweger syndrome 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 also may occur.

Causes of Zellweger Syndrome

It is caused by changes, or mutations, in any of the various genes that are involved in the proper function and creation of peroxisomes. These are the structures that are in the cells that are involved in many chemical processes which the body needs in order to function correctly. At this time there are twelve different genes known but there could be more. This makes Zellweger syndrome a disorder that is referred to as an autosomal recessive condition which means that this is just one of many different ways that a disorder can be passed down in families.

When a person has an autosomal recessive disorder there are two copies of the abnormal gene that has to be present in order for the disorder to develop. These structures in the cells are what are responsible for the production of certain lips that are important to digestion and your nervous system and for the proper breakdown of the fatty acids. They are also parts of waste disposal plus they help with the function and development of their brain. It is considered as a congenital or hereditary disorder that is rare. When one or both parents are carriers of any of these abnormal genes there is a twenty-five percent chance that they will have a child with Zellweger syndrome so this is why genetic counseling is so important before the woman becomes pregnant. With each pregnancy the woman has there is a one in four chances she will have a baby with Zellweger syndrome.

Zellweger syndrome Symptoms

The symptoms of this disorder will normally become apparent either during the first few hours or first few days of their life. 

Some of the Zellweger Syndrome symptoms that the infant may have include:

  • Poor muscle tone called hypotonia.
  • Difficulties in feeding or having poor sucking abilities.
  • Seizures
  • Liver cysts along with liver dysfunction.
  • Loss of hearing and vision.
  • Some of the infants may have a head that is either abnormally large, called macrocephaly, or abnormally small called microcephaly.
  • Cataracts
  • Glaucoma
  • Nystagmus which is fast movements of the eyes that are not controllable.
  • Elevated levels of iron and copper in the their blood
  • Jaundice
  • Not having the ability to move
  • Gastrointestinal bleeding

There will also be distinct facial characteristics such as:

  • Having a flattened face.
  • Having a broad nasal bridge.
  • Having a high forehead.
  • Having up slanting palpebral fissures which is the space between the margins of their eyelids.
  • Having epicanthal folds which is the fold of their skin of the upper eyelid that that is over both or one of the inner angles of their eye.
  • Eyebrow ridges that are underdeveloped.
  • Eyes that are wide-set.
They may also have other facial characteristics. Many of the infants that have Zellweger syndrome may have skeletal abnormalities like having a big space between the bones of their bone spots and skull. Most of these infants show signs of mental retardation.

Diagnosis for Zellweger Syndrome

The distinctive shape of the head and face of the infant born with Zellweger syndrome provides a clue to the diagnosis. Zellweger syndrome causes the build-up of very-long-chain fatty acids (VLCFA), so a test for VLCFA can help confirm the diagnosis. This and other highly specialized biochemical and genetic tests can be done at certain testing centers.

Zellweger syndrome Treatment

At this time there is no known cure for Zellweger syndrome and in most cases the infant will die. There is also no standard course of treatment. Because this disorder happens during fetal development treatment to correct Zellweger syndrome after birth will be treating the symptoms. Any other treatment after birth to correct any of the abnormalities that happen with Zellweger syndrome is limited. The neurological and metabolic abnormalities have already happened and cannot be reversed or fixed. Because most of the infants with this disorder do not live past six months of life, the main treatment is making sure that they are kept comfortable. There are some infants that do live twelve months but most die from respiratory distress, liver failure, or gastrointestinal bleeding.

What is the prognosis?

The prognosis for infants with Zellweger syndrome is poor. Most infants do not survive past the first 6 months, and usually succumb to respiratory distress, gastrointestinal bleeding, or liver failure.

What research is being done?

The National Institute of Neurological Disorders and Stroke (NINDS), and other institutes of the National Institutes of Health (NIH), conduct research exploring the molecular and genetic basis of Zellweger syndrome and the other PBDs, and also support additional research through grants to major research institutions across the country. Much of this research focuses on finding better ways to prevent, treat, and ultimately cure disorders such as Zellweger syndrome.