|Finding A Cure for Mitochondrial Diseases
Selected Case Studies of those with Mitochondrial Diseases from a Paper by Dr. Cohen
Improper mitochondria function can present a plethora of diverse clinical symptoms, and a few of these from a paper written by Dr. Cohen are given below:
1. 1982 DF was born at term and had no problems until she was 4 months old when it was found she was anemic during an evaluation for fever. She had multiple courses of antibiotics for UTIs and otitis media. She developed a picture of overwhelming sepsis and her lactic acid was elevated at 12 mM. She subsequently went on to have a chronic sideroblastic anemia, pancreatic failure, cardiac dysfunction, hearing loss, ptosis, myopathy and retinal degeneration. She died at the age of 15 from cardiac failure. Her mtDNA showed a typical deletion seen in Kearn Sayre syndrome.
2. 1984 CP was born at term weighing 1900 gm after an uncomplicated pregnancy, labor and delivery. He had mild dysmorphic features, along with the fact he was SGA, with rocker bottom feet, small upturned nose and epicanthal folds. He was noted to be hypotonic at birth and at 19 hours of life had his first seizure. His initial evaluation showed a metabolic acidosis with a lactic acid of 6 mM, with a lactate to pyruvate ratio of 10:1. Seizures continued and he was transferred to our hospital. Over the next several days his acidosis worsened, and fluids of D10+ 1/2 Normal bicarbonate were used to attempt to correct his acidosis. A urine organic acid showed enormous lactate excretion. A tentative diagnosis of pyruvate dehydrogenase deficiency was made, and the fluids were changed to a D2.5 solution with amino acids and intralipids. Within hours, the acidosis reversed and the child was extubated 2 days later. He was treated with high dose B1 and lipoic acid (stimulators of PDH), as well as with polycitra. He was given a regular infant formula with MCT oil and the lactic acid remained in the 4-6 mM range. He died in his sleep at 8 months of life. The E1-alpha subunit of PDH was absent. This is an X-linked disease.
3. 1984 A 7 day old boy was transferred to our hospital for jaundice. He was born at term without problems. He began regular infant feeds and ate will initially. He became jaundice at 3 days of life and was placed under bililights. He became increasingly lethargic and developed diarrhea. He was placed in an incubator for hypothermia, despite bundling him in blankets. He continued to bottle feed, despite his increasing lethargy. His bilirubin was as high as 15 with about 50% conjugated. On arrival the transport team checked his urine for reducing substances (positive) and glucose (negative). A tentative diagnosis of galactosemia was made and subsequently confirmed. He was treated with IV glucose and prophylactic antibiotics for a few days and recovered. He was started on a soy-based formula and did well until 3 weeks of life when he developed e. coli. sepsis. At this time (1999) he is alive and aside from learning problems, doing well on a lactose free diet.
4. S.K. 57 year old man came from India for evaluation of his cardiac conduction defect. His family history is significant for his mother dying at a young age of a cardiomyopathy, and that his brothers have similar problems to his. He was the president of a successful business in India. As a young man he was diagnosed with calcifying pancreatitis, and had been on replacement digestive enzymes for years. He has had numerous admissions for non-surgical bowel obstruction and has had several exploratory laporatomies, the etiology was never determined. Over the last 15 years he lost 75 pounds, and developed aching in his limbs. In January 1996 he was admitted for a stroke, and a cardiac evaluation determined he was in A-fib. He was placed on Coumadin. He was readmitted for a stroke several months later, and was again found to be in A-fib. His neurologist and cardiologist referred him to CCF Cardiology for placement of a pacemaker. In October 1996, after a 24 hour journey, he visited our cardiology department, and was told that a pacemaker was not indicated. While resting in the waiting room, trying to gather the energy to walk back to the hotel, he collapsed. He spent the next two weeks in a stupor in the NICU, and again, another stroke was detected, along with his A-fib. The patient was found to have an elevated lactate, ammonia and CK (MM). Polarography revealed decreased oxidation of substrates that donate reducing equivulants to complex I and beta oxidation. An evaluation determined that he had a deficiency in carnitine palmitoyl transferase II activity. Treatment was started and included a low fat diet with frequent meals rich in complex carbohydrates, along with levo-carnitine, CoQ10 and other vitamins. He has had no further events since his hospitalization in October 1996. Comments: In order for the mitochondria to burn fats, the free fatty acid must first enter the mitochondrial inner membrane. CPT I catalyzes the conversion of the activated free FA (acyl CoA) + carnitine to the acyl-carnitine. A carnitine translocase exchanges the acylcarnitine across the inner membrane for a free carnitine molecule. CPT II catalyzes the conversion of the acyl-carnitine to the acyl-CoA and free carnitine. The acyl-CoA can then enter the beta-oxidation spiral. CPT II deficiency usually results in exercise intolerance, muscle cramping and fatigue in young adults, but is also known to cause an early cardiomyopathy.
the above is from http://www.umdf.org/pdf/MITOCYTO.PDF