About "PBD's" ...

Definitions:
IRD is part of a group of rare genetic disorders known as Peroxisome Biogenesis Disorders or PBDs. Three disorders are considered to be part of this group: Infantile Refsum Disease (IRD), Neonatal Adrenoleukodystrophy (NALD) and Zellweger Syndrome (ZS). These disorders all share a similar cause but vary in their severity, with ZS being the most severe form and IRD at the milder end of the spectrum. The PBDs are also sometimes known as the Zellweger spectrum of disorders.

Causes:
PBDs result from defects in the assembly of a cellular structure called the peroxisome, found in all cells but particularly concentrated in the liver and kidneys. Peroxisomes perform a number of important functions in the body, including the breakdown of certain harmful substances such as Very Long Chain Fatty Acids (VLCFAs), phytanic acid and others. They are also involved in the synthesis of many crucial elements required by the body, for example the essential fatty acid docosahexaenoic acid (DHA), necessary for the proper functioning of the nervous system.

There are at least 12 genes required for correct assembly of the peroxisome and defects in any of these result in PBDs. The nature of the genetic defect determines the severity of the condition - patients with IRD have a lesser defect with peroxisomes retaining some function; however patients with ZS have a severe defect, resulting in essentially non-functional peroxisomes. PBDs can only be inherited if both parents carry the diseased gene. Their children will have a 25% chance of being affected by a PBD, a 50% chance of being a carrier and a 25% chance of being genetically normal.

Living with PBDs:
The impact on a child and their family is devastating from pre-diagnosis through every stage of the disease. In general many of the major systems of the body are affected by the PBDs, including the eye, liver, kidney, cartilage, heart and muscles. However the number and combination of clinical characteristics is highly variable.

Infants with ZS are severely impaired and will rarely survive the first year of life, having typically made little developmental progress. NALD and IRD are degenerative in nature and the clinical course may include eyesight, hearing and muscle tone problems, learning difficulties, mental impairment, liver and kidney dysfunction, seizures and other associated problems. Patients with NALD can survive into childhood, whilst patients with IRD can survive into the second decade of life and sometimes longer.

Treatment:
There is no cure for the PBDs and treatment of patients focuses on symptomatic therapy and support. Experimental therapies with docosahexaenoic acid (DHA) are being studied and improvement has been reported in some patients. Another approach being tested is bile acid therapy, which may help with liver function.