Shy-Drager Syndrome

Background

Shy-Drager Syndrome, also known as multiple system atrophy with autonomic failure (link)is a progressive neuromuscular disease with adult onset. Find out how many people have Shy-Drager Syndrome. It is related to Parkinson's disease, but differs in that Shy-Drager causes degeneration of the autonomic nervous system (link).



According to Medline Plus, Shy-Drager Syndrome is characterized by:

• Progressive damage to the nervous system, leading to low blood pressure when standing, difficulty urinating, and abnormal breathing during sleep
• Muscle tremor and rigidity
• Slow movement
• Disrupted REM sleep patterns

Genetics

Perhaps due to symptomatic heterogeneity, it has been suggested that Shy-Drager syndrome is genetically heterogeneous (link). However, Weidemann et al (2002) showed that a point mutation (Ala280Val) in the histamine H3 receptor (HRH3) gene was found in a Shy-Drager patient. Here's the abstract of the paper:

Neurotransmitter release is modulated by presynaptic histamine H(3) receptors located on histaminergic, noradrenergic and other nonhistaminergic neurons of the central and peripheral nervous system. Here, we report the determination of the structure of the human histamine H(3) receptor gene (HRH3) and the identification of a missense mutation (Ala280Val) in a patient with Shy-Drager syndrome. The coding region of the gene consists of three exons interrupted by two introns of approximately 1 kb in size. Exon boundaries only partly correspond to transmembrane domain organization. The homozygous Ala280Val variation in the third intracellular loop of the histamine H(3) receptor of a patient with Shy-Drager syndrome may be related to the etiology of the illness due to altered norepinephrine release. Furthermore, knowledge of the gene structure allows the verification of alternative splicing of the receptor. The corresponding histamine H(3) receptor isoforms as reported for the guinea pig and rat histamine H(3) receptor in different brain regions are not found in the human brain.

Here's a link to the Genbank entry for the HRH3 gene. This gene is different than genes involved in other types of orthostatic hypotension, such as dopamine beta-hydroxylase and the orthostatic hypotension candidate gene human renal urea transporter-2 (UT-2) gene.


Homologs in other organisms (link)

• P.troglodytes LOC458385 similar to Histamine H3 receptor (HH3R)
• M.musculus Hrh3 histamine receptor H 3
• R.norvegicus Hrh3 histamine receptor H3
• G.gallus LOC428147 similar to histamine H3 receptor H3S isoform

Here's a list of more general information about orthostatic hypotension:

Orthostatic Hypotension, by Dr. Timothy Hain

NINDS web entry for orthostatic hypotension

Because its symptoms (low blood pressure, dizzyness when standing) are similar to side effects of blood pressure-lowering drugs and some antidepressant drugs, and can be evoked by prolonged bed rest or dehydration, the underlying causes of orthostatic hypotension can be difficult to diagnose. The Wrong Diagnosis web site has much interesting information for patients and families about diagnosing the underlying causes of orthostatic hypotension.


The first place I looked for information about Shy-Drager Syndrome was the Entrez search engine at NCBI. There are 626 articles currently available about SDS; the first one was published in 1960 (Shy and Drager, 1960). Google searches for "Shy-Drager Syndrome" and "orthostatic hypotension" were also very useful.