Wednesday 13th October - Diagnosis Day explanation of the illness

Mummy and Daddy met with the Metobolic consultant Dr Morris. He has confirmed my illness. :-(

The Zellweger Spectrum:

Zellweger Syndrome, Neonatal Adrenoleukodystrophy (NALD),
and Infantile Refsum’s Disease (IRD)

The disorders of the Zellweger spectrum result from defects in the assembly of a cellular structure called the peroxisome, and are therefore also sometimes called the peroxisome biogenesis disorders, or PBDs. There are three disorders considered to be part of the Zellweger spectrum: Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). While these disorders all share a similar cause, they reflect varying degrees of severity of disease.

What causes the Zellweger spectrum of diseases?

As we mentioned, disorders of the Zellweger spectrum are caused by defects in the assembly of the peroxisome. There are at least 12 genes required for proper assembly of the peroxisome. Defects in any of these 12 genes result in disorders of the Zellweger Spectrum.

This peroxisome is one of four special compartments within all human cells. These individual compartments are separated from the rest of the cell by a membrane (a "wall" made up of fats and proteins). The peroxisome performs a number of important jobs within the cell that are needed to break down certain types of fats, to produce hormones, and to help the nervous system work properly. In order for it to properly do its job, the peroxisome must be correctly assembled.  If it is not, then it results in one of the diseases of the Zellweger spectrum.

What are the clinical symptoms of the Zellweger spectrum of diseases?

The disorders of the Zellweger spectrum are congenital (present at birth). Patients with Zellweger syndrome have consistent clinical characteristics, listed below along with a clarification of the clinical terms as necessary. The exact number and combination of clinical characteristics is highly variable. In general, many of the major systems are affected, including the eye (many vision difficulties), the liver (enlarged), the kidney, the cartilage, the heart (malformation of the cardiovascular system), and the muscles.

What are the differences between ZS, NALD, and IRD?

The difference between these disorders is one of severity. Patients with ZS rarely survive the first year, patients with NALD can live into childhood, while patients with IRD can survive even longer; sometimes into adulthood.

At a genetic level, the severity of the disease depends on the severity of the defect in the protein. Patients with IRD have a lesser defect, resulting in peroxisomes retaining some function. However, patients with ZS have a severe defect, resulting in essentially nonfunctional peroxisomes. This phenomenon produces the range of severity of the disorders.