Infantile Refsum Disease

PEROXISOME BIOGENESIS DISORDERS:
ZELLWEGER SYNDROME, NEONATAL ADRENOLEUKODYSTROPHY,
INFANTILE REFSUM DISEASE, AND
RHIZOMELIC CHONDRODYSPLASIA PUNCTATA

Welcome to the Infantile Refsum Disease website.

We, John Harris and Mary Stephens, are the parents of a wonderful little boy named Ian who is diagnosed with infantile Refsum disease (IRD). Ian was born in March of 1993. We live in Vancouver, Washington, USA, a small city just north of Portland, Oregon.

The pages that follow are meant to be a source of information and support to parents and caregivers of children diagnosed with Peroxisome Biogenesis Disorders (PBDs, sometimes also called Peroxisome Assembly Disorders). We have no medical advice.

A peroxisome is small compartment ("organelle") within a cell where particular chemical reactions take place, a sort of isolation chamber in which certain types of substances are taken in and processed.  Biogenesis refers to the genetic steps involved in the correct formation of these organelles. There are currently - in humans - a dozen or so different genes known to be necessary for this to occur, and mutations of any of them can can cause either complete failure, or the incorrect formation, of peroxisomes. Without correctly formed and functioning peroxisomes, a number of important chemical processes within the cell do not occur as they should, leading to a group of severe and often fatal diseases, the PBDs.

There are four PBDs - Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD) and rhizomelic chondrodysplasia punctata (RCDP). The first three are really a single spectrum of disease, genetically and chemically almost indistinguishable; and particular diagnosis is as much as anything based on the degree of  severity of the child's condition. ZS is the most severe form, IRD the least, with NALD in the middle. These three diseases are known as the Zellweger spectrum, and affected children share a common set of abnormalities and disabilities. There is a great deal of clinical overlap between them, with  no hard and fast lines.

RCDP is the fourth PBD, and affected children have some things in common with those in the Zellweger spectrum, but there are distinct differences and it's thought of separately.

There are several other peroxisomal diseases which are not PBDs, but result from the failure or deficiency in just one chemical process in otherwise normally functioning peroxisomes. These are the peroxisomal "single-enzyme" disorders. One of these diseases, x-linked adrenoleukodystrophy (X-ALD), is well-known from the film "Lorenzo's Oil". Another one of the single enzyme disorders is Refsum disease, from which infantile Refsum disease has taken its name. However, Refsum disease and IRD are two entirely separate disorders and should not be confused. Adult-onset (classical) Refsum disease results from the failure of just one peroxisomal process, the breakdown of phytanic acid. IRD results from a general failure in the correct formation of the peroxisomes themselves, and all peroxisomal processes are absent or deficient.

There are no cures for any of these diseases, PBD or single-enzyme. What therapies do exist, or have been attempted in the past, have been based on the general idea that the biochemical abnormalities and imbalances caused by defective peroxisome function lead to the pathology and disabilities of the diseases; and that therefore these can maybe be alleviated by artificially correcting the chemistry. One widely-practiced form of this is in dietary therapies which attempt to eliminate from the child's diet things which she can't properly deal with, specifically very long chain fatty acids (VLCFAs) and phytanic acid. When these aren't broken down (processes which occur in normal peroxisomes) they accumulate in a cell's membranes and lead to malfunction, disease, and even death of the cell. This VLCFA/phytanic acid diet may be the most commonly employed approach to therapy among all children with PBDs, however there are variations even within the general framework, and there is no single diet that all the children adhere to.

Another common approach is in supplementing the child's diet with docosahexaenoic acid (DHA). DHA is a highly unsaturated 22-carbon fatty acid which is relatively abundant in the membranes of certain cell-types, especially in the retina and brain. It is established with near certainty that DHA is necessary to the correct development and function of visual and neurological systems. Normally, we synthesize DHA for ourselves (from the essential fatty acid alpha-linolenic), the final step taking place in the peroxisome. Children with PBDs are deficient in DHA for this reason, a fact first noticed by Dr. Martinez in Barcelona, Spain, who began giving DHA to her patients in 1991, on the hypothesis that since low DHA levels were associated with visual and neurological problems, it would possibly be beneficial to supplement PBD children with it, to possibly alleviate just those problems. Currently, many children with PBDs are taking DHA, through a variety of sources, sometimes in conjunction with another fatty acid, arachidonic acid (AA).

Two other relatively common supplements are vitamin K, to control the slow blood coagulation times often associated with the PBDs (to prevent hemorrhage); and steroid hormones, to correct for another common problem, adrenal insufficiency.

There are children who are taking bile acids, which is another typical peroxisomal deficiency causing fat absorption problems, and there is on-going investigation into the benefits of this treatment.

There are currently, or have been in the past, other avenues of exploration: giving the kids plasmalogens (a specialized kind of lipid which is necessary to the structure and function of many types of cells, and which is another deficiency in the PBDs); trying to jump-start the production of peroxisomes with a class of drugs known as peroxisome proliferators; treatment with plasmapheresis, which is a sort of blood-filtering; and at least one known case of a liver transplantation.

Again, none of these things are cures, none of them will "fix" the underlying genetic defect that prevents the proper formation of
peroxisomes. They are each attempts at dealing with some specific chemical abnormality, or (in various combinations) with some specific set of chemical abnormalities. Some are taken to have generally established benefit, some have led to no successful treatments. In this regard, we would like to state that this website offers no endorsements. It is intended to offer information and references to further sources of information. It is up to each parent to consult with their own doctors, to do their own research, and to reach their own decisions about what is best for their child and their family, and which therapies (if any) to follow.

To all parents and caregivers: we are a small group, these are rare diseases, we would love to hear from all of you. Over the years that this website has been in operation, we have been contacted by a number of families from all over the world, and we maintain an informal e-mail list through which we all remain in regular contact, sharing information and support. We're a friendly bunch, all in the same boat, and cordially invite you to join us.

The IRD website is the independent project of John Harris and Mary Stephens, who are responsible for all content. This website is not associated with any formal organization, institution, or registered charity, although we wholeheartedly support the purposes and aims of a number of them.



You will find more information on the following pages :

IAN'S STORY :  More about our son, the joy of our lives, and the reason for these pages.

DEAFBLINDNESS :  Deafblindness; otology and auditory impairment; ophthalmology and visual impairment.

MEDICAL LINKS : Medical information, professional organizations, and family support groups.

PARENTS PRIDE : A page dedicated to all the children with peroxisomal disorders.  With pictures of some beautiful kids.
Parents' Pride Page 2: More photos

PEROXISOMAL DISORDERS : A general overview of the diseases, with references and bibliography.

BEYOND THE DIAGNOSIS : A mother's story of grief, joy and love.

FAMILY PAGE : Just in case someone might want to see what we look like. There is no social relevance to this page



Other sites of interest:
 
THE PBD PROJECT:  The PBD Project is an Australian registered charity engaged in fundraising to support existing and future research into the peroxisomal biogenesis disorders. For further information contact Vanessa Eilert:
vanessaeil@hotmail.com

LEUKODYSTROPHY REFERENCE SITE: Thanks to Joe Johnson

CHILDREN'S DEAFBLIND HOME PAGE : For stories of other deafblind children

REFSUM'S DISEASE : For those who got to this page looking for information on Adult Refsum's disease, this is a link to a site in Australia that deals with that disorder specifically.

JUSTIN'S PAGE : The webpage of a Canadian family whose son is diagnosed with Zellweger syndrome.
In French and English.  Thanks to Gaetan and Tina Comeau.

ZELLWEGERSYNDROME.ORG :  The website of a family in Ohio whose son is diagnosed with Zellweger syndrome.
This site currently under construction, and planned to include medical, educational, family support, and financial resource information. Thanks to Mark and Dana Matt.

IRD WEBRING HOMEPAGE: The homepages of other families of children with IRD and other peroxisomal disorders.
Thanks to Debbie.

"OUR LITTLE ANGELS" : Ernest Batey's website dedicated to families and their children living with peroxisomal disorders. More links to family pages, stories and photos.

"OUR BEAUTIFUL CHILDREN" :  Another webring of the homepages of families having children with peroxisomal biogenesis disorders. Thanks to Kiza Steward.

Note: Debbie, Ernest Batey, and Kiza Steward are all willing and happy to prepare family homepages for inclusion on these webrings. Interested families are encouraged to contact any of them directly through their respective websites for information regarding this.




To contact us by
email
click here
or you can mail
us at
Stephens/Harris
6004 NE 108th Avenue
Vancouver, Washington  USA  98662
(360) 891- 5878

The IRD website was established February 1997
Last updated 16 April 2003
No Crisis

1305 +


Deaf, dumb and blind boy
He's in a quiet vibration land.
Strange as it seems, his musical dreams
aren't quite so bad.

Ten years old
With thoughts as bold as thoughts can be.
Loving life and becoming wise
In simplicity.

Sickness will surely take the mind
Where minds cannot usually go.
Come on the amazing journey
And learn all you should know.

A vague haze of delerium
Creeps up on me.
All at once a tall stranger I suddenly see.
He's dressed in a silver sparkled
Glittering gown
And his golden beard flows
Nearly down to the ground.

Nothing to say and nothing to hear
And nothing to see.
Each sensation makes a note
in my symphony.

Sickness will surely take the mind
Where minds cannot usually go.
Come on the amazing journey
And learn all you should know.

His eyes are the eyes that
Transmit all they know.
Sparkle warm crystaline glances to show
That he is your leader
And he is your guide
On the amazing journey
Together you'll ride.

[Amazing Journey - Pete Townshend,
from the opera "Tommy" -  - The Who, 1969]