I went back to the geneticist this morning, and all of my testing is back. It appears as though I have a mitochondrial disease, probably. They say "probably" because it seems I have one that is yet to be pinpointed. Yep, I like to make things difficult. :-) The doctor compared it to having a disease that won't be diagnosed until the next generation. It was really strange, she said, looking at my test results, because one amino acid or something would be normal but then another would be almost zero and they shouldn't be or whatever and it was just so fascinating. It amazes me that anyone who knows anything about the human body could ever NOT believe in God. We are just too intricately created! We talked at length and the bottom line is this is way beyond even what they do, so they are emailing one of the top mitochondrial specialists in the world, Dr. Cohen, who is located at...that's right! Cleveland Clinic! He will look over all of my info and hopefully elect to see me. In the mean time, I will continue to take it easy as needed, since over-doing it is bad for mitochondrial disease, and be thankful that we are finally, maybe, getting answers. For those who want for info on mitochondrial disease, here is info from the United Mitochondrial Disease Foundation:
What is Mitochondrial Disease
Mitochondrial diseases result from failures of the mitochondria, specialized compartments present in every cell of the body except red blood cells. Mitochondria are responsible for creating more than 90% of the energy needed by the body to sustain life and support growth. When they fail, less and less energy is generated within the cell. Cell injury and even cell death follow. If this process is repeated throughout the body, whole systems begin to fail, and the life of the person in whom this is happening is severely compromised. The disease primarily affects children, but adult onset is becoming more and more common.
Diseases of the mitochondria appear to cause the most damage to cells of the brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems.
Depending on which cells are affected, symptoms may include loss of motor control, muscle weakness and pain,
gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis, developmental delays and susceptibility to infection
Energy Factories and Much MoreThe conventional teaching in biology and medicine is that mitochondria function only as "energy factories" for the cell. This over-simplification is a mistake which has slowed our progress toward understanding the biology underlying mitochondrial disease. It takes about 3000 genes to make a
mitochondrion. Mitochondrial DNA encodes just 37 of these genes; the remaining genes are encoded in the cell nucleus and the resultant proteins are transported to the mitochondria. Only about 3% of the genes necessary to make a
mitochondrion (100 of the 3000) are allocated for making ATP. More than 95% (2900 of 3000) are involved with other functions tied to the specialized duties of the differentiated cell in which it resides. These duties change as we develop from embryo to adult, and our tissues grow, mature, and adapt to the postnatal environment. These other, non-ATP-related functions are intimately involved with most of the major metabolic pathways used by a cell to build, break down, and recycle its molecular building blocks. Cells cannot even make the RNA and DNA they need to grow and function with out mitochondria. The building blocks of RNA and DNA are purines and pyrimidines. Mitochondria contain the rate-limiting enzymes for pyrimidine
biosynthesis (
dihydroorotate dehydrogenase) and home synthesis (d-amino
levulinic acid
synthetase) required to make hemoglobin. In the liver, mitochondria are specialized to detoxify ammonia in the urea cycle. Mitochondria are also required for cholesterol metabolism, for estrogen and testosterone synthesis, for neurotransmitter metabolism, and for free radical production and detoxification. They do all this in addition to breaking down (oxidizing) the fat, protein, and carbohydrates we eat and drink.
Defining Mitochondrial
DiseaseMitochondrial diseases are the result of either inherited or spontaneous mutations in
mtDNA or
nDNA which lead to altered functions of the proteins or RNA molecules that normally reside in mitochondria. Problems with mitochondrial function, however, may only affect certain tissues as a result of factors occurring during development and growth that we do not yet understand. Even when tissue-specific
isoforms of mitochondrial proteins are considered, it is difficult to explain the variable patterns of affected organ systems in the mitochondrial disease syndromes seen clinically.
Genocopies of Mitochondrial DiseaseBecause mitochondria perform so many different functions in different tissues, there are literally hundreds of different mitochondrial diseases. Each disorder produces a spectrum of abnormalities that can be confusing to both patients and physicians in early stages of diagnosis. Because of the complex interplay between the hundreds of genes and cells that must cooperate to keep our metabolic machinery running smoothly, it is a hallmark of mitochondrial diseases that identical
mtDNA mutations may not produce identical diseases.
Genocopies are diseases that are caused by the same mutation but which may not look the same clinically.
Phenocopies of Mitochondrial DiseaseThe converse is also true: different mutations in
mtDNA and
nDNA can lead to the same diseases. In genetics, these are known as
phenocopies. A good example is Leigh syndrome, which can be caused by about a dozen different gene defects. Leigh syndrome, originally a
neuropathological description of the brain of one affected child, was described by Denis Leigh, the distinguished British physician, in 1951. It is characterized by bilaterally symmetrical MRI abnormalities in the brain stem, cerebellum, and basal ganglia, and often accompanied by elevated lactic acid levels in the blood or
cerebrospinal fluid. Leigh syndrome may be caused by the
NARP mutation, the
MERRF mutation, complex I deficiency, cytochrome
oxidase (COX) deficiency,
pyruvate dehydrogenase (
PDH) deficiency, and other unmapped DNA changes. Not all children with these DNA abnormalities will go on to develop Leigh syndrome, however.
Mitochondrial diseases are even more complex in adults because detectable changes in
mtDNA occur as we age and, conversely, the aging process itself may result from deteriorating mitochondrial function. There is a broad spectrum of metabolic, inherited and acquired disorders in adults in which abnormal mitochondrial function has been postulated or demonstrated.
Adapted/selected sections from Robert
Naviaux's "Overview, the Spectrum of Mitochondrial Disease" in the
Mitochondrial and Metabolic Disorders, Primary Care Physician's Guide, second edition.
