Mitochondria are minute organelles that serve to stabilize intracellular levels of calcium and play a prominent role in mediating a certain type of cell-death, the latter called apoptosis. However, the best known function of these organelles is their role as the so-called powerhouses of the cell. With the sole exception of red blood cells mitochondria are found in all cells of the body. Their role in energy production ties them to almost every cellular process imaginable. When mitochondria do not work properly the resultant lack of energy translates into observable symptoms. These symptoms include, among many others, slowed growth, muscle weakness, paralysis of eye movements, heart/liver disease, diabetes and neurological problems. In some affected females repeated mid- and late pregnancy abortions may be the presenting symptom. For unknown reasons mitochondrial disorders may target a particular organ or many of them. Disturbances in mitochondrial function have been related to a number of clinical conditions, some of which are associated to gene defects but many still of unknown origin.
The figure illustrates some of the organs usually affected by mitochondrial disorders.
Mitochondrial conditions and its relation to autism spectrum disorders (ASD) acquired a lot of attention after a young girl named Hannah Poling received compensation by the federal vaccine court. Hannah developed normally until she received a series of vaccines. Ever since she lost her vocabulary, eye contact and exhibited stereotypical behaviors all typical of autism. The CDC clarified the court’s ruling by specifying that vaccines in this case were not the cause of “autism”. Rather a preexisting condition (in this case mitochondrial disorder) provided for a generalized brain disorder (or encephalopathy) that had many manifestations including those of autism.
I must say that I know Jon and Terry Poling, the parents of Hannah. Jon did his Neurology residency at Johns Hopkins and some of his witnesses are close friends and esteemed colleagues. I do not believe that Jon necessarily blames the mercury in vaccines, nor denies the benefits of vaccines accrued throughout recorded medical history. However, he would argue that in certain children with known genetic or metabolic vulnerabilities revising the vaccination schedule would be a prudent alternative.
There are many metabolic disorders associated with autism-like symptoms, e.g., phenylketonuria (PKU), disorders of purine metabolism, biotinidase deficiency. Probably the most common of all of these are mitochondrial disorders. Studies suggest that the prevalence of mitochondrial disorder in ASD approximates 5%. Broadening the diagnostic criteria, and increasing inclusion of atypical cases, provides for a prevalence rate of about 40%. Diagnosis is based, in part, on morning fasting levels of different metabolites including lactic acid, pyruvic acid, acyl-carnitine, and ammonia. In some cases targeted gene testing or even a skin and muscle biopsy may be needed in order to establish a diagnosis. There are no known treatments for mitochondrial disorders. However, preventive measures such as avoiding dehydration and treating fevers may be of some benefit.
I have previously mentioned that the cerebral cortex is composed of modular units called minicolumns. These units act as the microprocessor of a computer. In autism, the cerebral cortex has many more minicolumns albeit developmentally malformed. Similar to mitochondrial disorders, the cerebral cortex of autistic individuals could malfunction when exposed to metabolic exigencies (see https://corticalchauvinism.wordpress.com/2013/01/29/what-causes-the-mayor-symptoms-of-autism-part-1/).
In summary, the main observation of this blog is that mitochondrial disorders were once considered a rare cause of autism but broadening of the criteria suggests a higher than expected prevalence. Although the threshold has to be low when ordering diagnostic tests for mitochondrial disorders, trying to predict who may or may not have a mitochondrial disorder is fraught with limitations. Many of the symptoms characteristic of mitochondrial disorders are common to autism: cognitive impairment, motor and behavioral disturbances, seizures. Furthermore, once you obtain a positive diagnosis, treatment options are limited. However, there is hope that in the near future new modes of therapy will make a difference in the quality of life of these patients. Results of clinical trials (http://www.sciencedirect.com/science/article/pii/S1096719211003787) testing new drugs have offered promising results.
[4/15/2013 Addendum: At a Think Tank in Maryland Dr. Richard Frye stated that autistic patients with mitochondrial disorders had a more prominent history of motor delays and a higher prevalence of seizures that idiopathic cases. Contrariwise, the prevalence of hypotonia (diminished muscle tone) tends to be lower in patients with mitochondrial conditions as compared to idiopathic autism. Dr. Robert Naviux added the importance of abstaining from using valproic acid (Depakote) in this patients population. Valproic acid is an anticonvulsant but its use has been associated with increased oxidative stress and mitochodrial dysfunction, see http://toxsci.oxfordjournals.org/content/86/2/436.abstract%5D