INVITED SPEAKERS / COMUNICAÇÕES POR CONVITE

 

CC-04

An Introduction to X-linked IMDS

 

 

Stephen Waldek^I

^IIndependent Medical Consultant, Manchester, UK. E-mail: stephenwaldek@yahoo.co.uk

 

 

While individually the inherited metabolic diseases are rare or very rare, overall the incidence is around 1:1,400 live births and accounts for about 15% of all single gene disorders. The vast majority of these diseases are inherited in a recessive manner with 3 or 4 being dominant conditions. However, 14 are inherited in an X-linked fashion. By my estimation there are over 200 conditions to consider, most of which are not treatable. My presentation will focus on four diseases—AndersonFabry disease (FD); Mucopolysaccharidosis type II (MPS II); Ornithine Transcarbamylase deficiency (OTC); and X-Linked adrenoleucodystrophy (XALD)—that illustrate several points of interest.

FD is a multi-system disease caused by a deficiency of the lysosomal enzyme alpha galactosidase. Accumulation of the substrate globotriaosylceremide (GL3) leads to a sequence of symptoms over time starting with severe neuropathic pain in the peripheries and moving on to proteinuria renal failure, cardiac and cerebrovascular disease. Without treatment death occurs by the 4th or 5th decade. Fortunately, enzyme replacement therapy is available. The clinical and therapeutic aspects of the disease will be discussed as well as the issue of late onset disease and the fact that there is a very high incidence of symptoms in the so called female carriers.

MPS II, or Hunter syndrome, is another multisystem lysosomal storage disorder caused by a deficiency of iduronate2-sulphatase. The main features are due to skeletal involvement and like FD there is enzyme replacement therapy. However, unlike FD it is exceptionally rare for female carriers to develop symptoms or signs of the disease.

OTC is the commonest of the urea cycle defects. The symptoms are related to the accumulation of ammonia and will be discussed. In most boys the disease presents in the neonatal period. Many do not survive and those that do are usually severely brain damaged and susceptible to destabilization throughout their lives, even with the dietary treatment currently available. Interestingly, as will be discussed, about 15% of females will develop symptoms and require lifelong treatment. One of the times of greatest risk is during pregnancy and delivery.

The presentation will also describe the various manifestations of XALD from the severe childhood presentations to the adrenal and neurological disease of the onset in older boys and young men.

In addition to the clinical aspects of the four diseases, information on diagnosis and genetic counselling implications will be discussed.