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 CRPS-I.

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:

1. 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.
2. 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.
3. 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:

1. If each participant meets the international criteria for a diagnosis of CRPS
2. How common functional disorders of all kinds are in CRPS-I sufferers.
3. How common functional disorders of all kinds are in the relatives.
4. 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 determine:

1. 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 changes.
2. 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.