MNGIE (mitochondrial neurogastrointestinal encephalo- myopathy) is a rare disease caused by mutations in the gene encoding thymidine phosphorylase, which is an enzyme that regulates levels of molecules called nucleosides (specifically thymidine and deoxyuridine). Extremely high levels of these nucleosides are toxic and have damaged Michael's nervous system and muscles. The disorder presents with severe gastrointestinal dysmotility along with loss of sensation and severe weakness. At present, Michael is no longer able to walk, has - for the most part - lost the use of his hands and feet, and is unable to eat therefore he is entirely dependent upon TPN (intravenous feeding).

He was recently hospitalized at the Children's National Medical Center in Washington, DC for 3 and a-half months and was discharged due to insurance issues when Empire Blue Cross Blue Shield rejected the request for Certification of Admission for a bone marrow transplant (which had been scheduled for January 26th of this year). Appeals to the FEP Plan Director's Office in Washington DC, as well as to the Office of Personnel Management, resulted in the upholding of the rejection for insurance coverage. Michael's disease is progressing and will ultimately lead to his death.

Dr. Michio Hirano of the Columbia University College of Physicians and Surgeons in New York is the leading expert on the disorder. Together with colleagues in Spain and Israel, he has done research, which indicates that platelet infusions can replace thymidine phosphorylase and significantly reduce levels of thymidine and deoxyuridine in MNGIE patients. Although the benefits of platelet infusions are transitory, these data indicate that bone marrow transplantation may be a viable therapy to correct the disorder. Much of the research supporting bone marrow transplantation (BMT) is yet to
be published. The fact that the research is not yet published (although a manuscript is being prepared) has proven to be problematic especially with our insurance company which has rejected the request for BMT because the company considers the treatment to be an experimental procedure for a
rare disease that is not listed in the insurance plan brochure.

MNGIE is such a rare disorder (fewer than 100 laboratory confirmed cases worldwide) that it is not even listed among the 1100 rare diseases on the National Organization for Rare Disorders website. How can research and treatment of MNGIE ever expand beyond the current efforts by Dr. Hirano and his colleagues? Because MNGIE is so uncommon, it is difficult to obtain major research funding for this disease. Pharmaceutical and biotechnology companies have been unwilling to develop therapies or support clinical trials for MNGIE. Our heath
insurer is unwilling to recognize the research data as viable reasons to cover Michael's BMT. Rejecting coverage, because Michael's disorder is not listed in the insurance plan brochure and BMT is not justified, is extremely disappointing and insensitive to the facts of this disease.

We are currently working and hoping for an admission date for Michael's transplant. Financial issues have certainly complicated that process.
(Note: The above text was edited by Dr. Hirano 5/15/05.)

Transplant Center
Children's Hospital of New York Presbyterian, New York City

Transplant Doctor
Dr. James H. Garvin, Jr., MD, PHD
Director of Pediatric Oncology and Hematology/ BMT
Director, Pediatric Neuro-Oncology
Columbia University Medical Center

Dr. Charles Hesdorffer
Professor of Clinical Medicine
Former Head of the Bone Marrow Transplant Service at the
Columbia University Medical Center
Dr. Hesdorffer, in consultation with Dr. Hirano, was instrumental in setting up a Stem-Cell (BMT) Transplant for Michael at Columbia

Neurologists:
Dr. Diana Escolar, Children's National Medical Center, Washington DC
Dr. Michio Hirano, College of Physicians and Surgeons, New York Presbyterian

Gastroenterologist:
Dr. Stuart Kaufman
Medical Director of the Intestinal Transplant Program
at Georgetown University and the Children's National Medical Center

Dr. Bryan Fine
Team Leader on 3 Orange and 3 Yellow
Children's National Medical Center