Vol. 8 Issue 9
This mitochondrial disease that runs in families often goes undiagnosed
Betty Eble, MSHR, BS, RN, CNA, FNE-A/P takes life at full speed. She is cochair of the Maryland Board of Nursing Standards and Practice Committee, treasurer of the Maryland/DC Chapter of the International Association of Forensic Nurses, project coordinator for the St. Mary's Hospital (SMH) Sexual Assault Forensic Examiner (SAFE) program, part-time patient care supervisor at SMH, and is in the process of becoming a parish nurse.
However, there was a time when a tragedy caused her to hit the brakes. A beloved niece, Mindy Cooper, LPN, suffered a seizure at age 27, was intubated and placed on a ventilator. Cooper was already living with a diagnosis of Wolff-Parkinson-White syndrome, a congenital problem that affects the heart's electrical network.1 As a teenager she had been treated with radiofrequency ablation for this condition. Cooper and her sibling were experiencing difficulties with their auditory centers as well and were wearing hearing aids. Physicians decided the auditory problem was a seizure disorder and prescribed medication. Yet, 1 year later, Cooper had another grand mal seizure. This time, a savvy neurologist looked at her history and sent her immediately to be evaluated for MELAS.
What Is MELAS?
MELAS is short for mitochondrial encephalopathy, lactic acidosis and stroke-like episodes. Mitochondrial diseases (for a list of these diseases, which include Alzheimer's, Parkinson's, GERD, myopathy and diabetes mellitus, go to www.mitoresearch.org/diseaselist.html) cause accumulation of organic acids, like lactic acid, in the blood. When sugars are utilized for energy in an anaerobic environment (no oxygen present) lactic acid is formed. Lactic acidosis is life-threatening.2
Every cell in the human body (except red blood cells) has small, intricate power plants called mitochondria that convert nutrients into energy to support life. These energy producers break down carbohydrates, fat and oxygen. The organs most dependent on this energy production are the brain, heart, skeletal muscle, kidney, endocrine glands and bone marrow. These systems are the most strained by mitochondrial diseases. The brain, especially, requires tremendous energy to function correctly and is often the target of mitochondrial disease.2
There is actually DNA in the human body that is not linked to any of the 46 chromosomes. Called the "other DNA," mitochondria DNA differs from the regular DNA because it is found outside of the cell nucleus in the cytoplasm. "Each mitochondrion has a chromosome made of DNA that is quite different from the better known chromosomes in the nucleus. The mitochondrial chromosome is much smaller; it is round (whereas the chromosomes in the nucleus are normally shaped like rods); there are many copies of the mitochondrial chromosome in every cell."3
MELAS and all mitochondrial diseases were a mysterious secret before the discovery of mutations in mitochondria's chromosomes. Many mitochondrial diseases are just now being discovered.
Who Is Affected by MELAS?
MELAS occurs from ages 4 to 40, though most patients show some symptoms before they turn 20. Patients have been known to survive into their 60s. Usually there is a childhood history of migraine and vomiting. Males and females are equally affected. Short stature and heart irregularities are common. Clinical diagnosis includes muscle tissue biopsy that shows "ragged red fibers" when viewed under the microscope. Elevated lactic acid levels in the blood and cerebral spinal fluid are an indication of MELAS.
Hemiparesis (weakness on one side of the body) is typical. Additionally, muscle weakness and movement disorders such as myoclonus and tremors are often present, therefore causing exercise intolerance and total limb weakness.
Psychiatric problems can range from dementia and personality disorder to depression. Impaired vision and hearing as well as blindness and deafness also are present in the syndrome. The most recognizable symptom of MELAS is a sudden headache followed by seizure activity.4
How to Diagnose
Imaging studies are helpful yet not often diagnostic. CT scan, MRI, single-photon emission computed tomography (SPECT) and positron emission tomography, each yield a small piece of the puzzle yet none are particularly diagnostic for MELAS. Other studies such as EEG can be helpful with diagnosing seizure activity.
Most mitochondrial disorders known to date are inherited in either an autosomal recessive or maternal manner. MELAS is caused by a DNA mutation that is maternally inherited via the ovum. The mother does not have to have symptoms to pass MELAS on to her children. When the mother has the mtDNA mutation, all of her children will inherit the disease-causing mtDNA mutation and may or may not have symptoms. In autosomal recessive inherited mitochondrial disorders, on the other hand, 25 percent of offspring will inherit the disease, 50 percent will inherit the gene and be unaffected carriers and 25 percent will not inherit the gene. The risk of passing on the disease for each pregnancy is 25 percent.5
Betty Eble along with family members were tested for the disease. Eble discovered at age 55 that she has subclinical MELAS. She had already been diagnosed with Hashimoto's disease, diabetes, osteoarthritis, muscle weakness, fibromyalgia, mitral valve prolapse and, in 1991, she suffered an MI. Her two sons and three grandchildren remain symptom-free. Betty's sister has hearing deficits and has had transient ischemic attacks. Her sister's daughter has type 1 diabetes and a hearing disorder. Betty's other sister has had a stroke, open-heart surgery, diabetes and uses bilateral hearing aids.
Three of that sister's four children have MELAS; Mindy Cooper, an LPN, is one of them. To date Cooper has had six strokes and is partially paralyzed on the right side. She is now 32 years old and has retired from nursing. It is due to Cooper's diligence in seeking a diagnosis that the quality of life for all of her family members has changed for the better.
Collection of Diagnoses
Why did it take so long to discover this disease in Eble's family? Probably because there isn't one single symptom that identifies MELAS; it is a collection of diagnoses. Mitochondrial disease should be suspected three or more organ systems are involved, short stature, vision and/or hearing loss, diabetes, muscle biopsy which has ragged red fibers, elevated lactic acid and pyruvate in the blood and cerebrospinal fluid, and/or neurological problems such as migraine or seizure disorders.6
Misdiagnoses include treating the effects of the disease such as stroke and not following up on the reason for the stroke. The complete clinical picture is hidden from all but the most attentive physicians. A more common muscular disorder, fibromyalgia has been mistakenly diagnosed for MELAS. "The clinical presentation of mitochondrial disease has many similarities with fibromyalgia . Mitochondrial disease, unlike fibromyalgia, is caused by abnormal oxidative metabolism of glucose within skeletal muscle, resulting in anaerobic conversion of pyruvate into lactate. The widespread production of lactate under aerobic conditions can produce objective muscular weakness that differs from the subjective symptoms associated with fibromyalgia."7
In addition to concerns of misdiagnosis, wrongly prescribed medications can cause harm to those who have MELAS. Metformin, used to treat diabetes by lowering the glycemic index, can cause lactic acidosis. "One of the first things I did was get off glucophage," Eble stated. "It increases lactic acid buildup and causes stroke." Valproic acid, an antiepileptic drug used in migraine therapy and psychiatric disorders, may make symptoms of MELAS worse.8
However, Eble lives each day to the fullest. She shocked coworkers by coming to work just 3 days after her heart attack. "I waved my doctor's note at the disbelievers and said, 'read it and weep!'" Eble shared. "I was not about to stay home and wallow in this."
Though there is no cure for any of the 38 known mitochondrial diseases, there are effective recommendations and treatment options to delay or halt disease progression:
• Fight fatigue and raise energy levels with vitamin therapy.
• Add cofactors (an element or coenzyme made by the body that forms links with
• acids and fatty acids and can make energy in chemical reactions), which may help slow the disease through antioxidant action.9
• Maintain adequate hydration at all times.
• Extend the range of movement in muscles with gentle physical therapy.
• Get plenty of rest, including naps in the afternoon and early to bed each night.
• Support research into mitochondrial diseases, including genetic therapies and the development of neuroprotectives.
For those with MELAS, there are things to avoid:
• Alcohol and cigarette smoking
• MSG (monosodium glutamate)
• Excess iron
• Additional vitamin C
• Severe heat loss, heat stress, direct sunlight and use of air conditioning
• Psychological stress
• Strenuous exercise
Research Seeking Answers
The discovery of mitochondrial disease is new to humanity. Though rare, its impact has huge repercussions for us all mitochondrial diseases play a part in aging. It is sobering to learn of the Mitochondria Research Society's estimate of 4,000 children born each year in the United States with mitochondrial diseases.
There is hope that genetic researchers will find the answer. According to the Children's Mitochondrial Disease Network, "Techniques for manipulating the mitochondrial genome are now being investigated. Whereas nuclear manipulation would necessitate treatment for life, manipulation of the mitochondrial genome would result in a one-off treatment, thus providing a 'cure' for mitochondrial disorders."2
1. University of Michigan Congenital Heart Center. (2005). Children's congenital heart services: Wolff-Parkinson-White syndrome. Retrieved August 30, 2005 from the World Wide Web: http://www.med.umich.edu/cvc/mchc/parwpw.htm
2. The Children's Mitochondrial Disease Network. (2005). Questions. Retrieved August 22, 2005 from the World Wide Web: http://www.emdn-mitonet.co.uk/questions.htm
3. Shiel, W. & Hecht, F. (2005). MELAS syndrome. MedicineNet.com. Retrieved August12, 2005 from the World Wide Web: http://www.medicinenet.com/melas_syndrome/article.htm
4. National Institute of Neurological Disorders and Strokes. (2005). Mitochondrial myopathies information. Retrieved August 20, 2005 from the World Wide Web: http://www.ninds.nih.gov/disorders/mitochondrial_myopathy/mitochondrial_myopathy.htm
5. United Mitochondrial Disease Foundation. (2005). The genetics of mitochondrial disease. Retrieved August 22, 2005 from the World Wide Web: http://www.umdf.org/mito_info/genetics.aspx
6. United Mitochondrial Disease Foundation. (2005). When to Suspect Mitochondrial Dysfunction. Retrieved August 22, 2005 from the World Wide Web: http://www.umdf.org/mito_info/symptoms.aspx
7. Medscape. (2005). Mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS): A mitochondrial disorder presents as fibromyalgia. Retrieved from the World Wide Web August 20, 2005 http://www.medscape.com/viewarticle/479898_print
8. Emedicine. (2005). Metabolic disease & stroke: MELAS. Retrieved August 12, 2005 from the World Wide Web: http://www.emedicine.com/NEURO/topic580.htm
9. United Mitochondrial Disease Foundation. (2005). Treatment. Retrieved August 22, 2005 from the World Wide Web: www.umdf.org/mito_info/treatment.aspx
Teresa Andrasik is a NICU nurse at George Washington University Hospital, Washington, DC. She is also coordinator of the Special Diet Support Group and a maternal/child nurse, both at St. Mary's Hospital, Leonardtown, MD