RSDSA and American RSDHope Award Research Grant to the Children's Hospital of Los Angeles
James W. Broatch, MSW, executive director of the Reflex Sympathetic
Dystrophy Association of America (RSDSA) and Lynne Orsini,
Executive Director of American RSDHope, have announced the
award of a $50,000 research grant to Richard Boles, MD, Director,
Center for Metabolic and Mitochondrial Disorders at the Childrens
Hospital Los Angeles. Dr. Boles and his team, Essam A. Zaki,
Ph.D. Post-doctoral Student, Erin E. Baldwin, MS Genetic Counselor,
and Katherine R. U. Heisner, BS, Research Assistant will study
Maternally inherited mitochondrial DNA sequence variants and
Their hypothesis is that is that a brain/nerve energy deficiency
that can be caused by maternally inherited changes in the
mtDNA code plays an important role in the development of many
functional disorders, including CRPS-I. The team will study
up to 300 individuals who have been diagnosed with CRPS-I
By a physician or other health care providers.
Dr. Boles explains his interest in this subject: "I
am a practicing pediatric geneticist/metabolic specialist,
as well as a medical researcher in mitochondrial genetics.
In my clinical practice, hundreds of families are followed
in which multiple matrilineal relatives suffer from neurological
disorders, especially intermittent functional conditions.
Our interest in complex regional pain syndrome type 1 (CRPS-I)
stems from the observation that, in addition to other functional
conditions, 12 of my patients have symptoms that meet all
of the international diagnostic criteria for CRPS-I. Examples
include a 9-year-old girl with severe pain, allodynia (touch
perceived as severe pain), swelling and color change to the
whole arm and hand for several weeks following an arm bone
fracture, and a 14-year-old girl with a change in sensation
and color in a stocking-like distribution, with full disability
secondary to allodynia following a fall during gymnastics
without noted fracture.
"All of those 12 children meet established clinical
criteria for the diagnosis of a mitochondrial disorder, and
almost all of the family histories are highly suggestive of
maternal inheritance. Beyond these 12 children, many more
of my patients with mitochondrial disease from families demonstrating
maternal-inheritance have frequent episodes of localized extremity
pain that doesn't quite meet the CRPS-I diagnostic criteria.
Many of their brothers, sisters and mothers have these episodes
of pain as well.
Why does this matter?
Identifying maternal inheritance and/or mtDNA sequence
changes that are more common in CRPS-I sufferers than in non-sufferers
is important as it would demonstrate that energy deficiency
is a part of what causes CRPS-I. In close partnership with
the Cyclic Vomiting Syndrome Association, our group has reported
in the last few years finding maternal inheritance and mtDNA
sequence changes in individuals with cyclic vomiting. Based
upon this, mitochondrial-directed treatments (such as frequent
feedings, D10-containing IV fluids in severe episodes, co-enzyme
Q10 and carnitine) have made a great impact on treatment for
cyclic vomiting. Our hope is that this research may lead to
similar successes in the management and treatment of CRPS-I.
Participants (or their parent/guardian) will be asked:
- To complete two questionnaires, each 5-pages long, which
mostly ask questions about CRPS-I, other sources of chronic
pain, fatigue and other functional conditions.
- To forward copies of the questionnaires to up to 6 of
their female relatives, ages 12-50 years old. Specifically,
participation is requested of up to 2 matrilineal relatives
(examples: sister, mother's sister), 2 non-matrilineal relatives
(examples: father's sister, brother's daughter) and 2 non-genetic-related
"in-laws" (examples: brother's wife, uncle's wife).
Teenage and adult women are being studied because of a higher
frequency of functional symptoms. Functional symptoms are
quite common in general among individuals over age 50, so
any genetic effects would be harder to identify.
- To provide us with a DNA sample by spiting into a special
container (CRPS-I patients only, not their relatives). It
is possible later that we may ask a few selected participants
if they would volunteer a blood sample.
Questionnaire data from patients and their relatives will
be studied to determine:
- If each participant meets the international criteria for
a diagnosis of CRPS
- How common functional disorders of all kinds are in CRPS-I
- How common functional disorders of all kinds are in the
- How CRPS-I might be inherited in families, in particular
how many families demonstrate maternal inheritance.
Mitochondrial DNA data from patients will be studied to
- If certain genetic changes we found that increase the
risk for developing cyclic vomiting and migraine also increase
the risk for the development of CRPS-I. We previously reported
on data linking the mtDNA control region with cyclic vomiting
and migraine. In addition, we very recently found that two
specific mtDNA sequence changes are quite frequent in cyclic
vomiting. One of these changes, in the mtDNA control region,
is found in about half of all adults with common migraine,
but in only about a fifth of the population in general.
We will start by testing the mtDNA, collected from saliva
samples, of CRPS-I individuals for these two novel mtDNA
- If there are any other mtDNA sequence similarities between
CRPS-I and multiple other functional conditions. All mtDNA
changes will be compared against a published-database of
several hundred "normal" mtDNA sequences.