mtDNA Disease in the Primary Care Setting

Abstract

Disorders of mitochondrial DNA (mtDNA) may commonly present to primary care physicians but go undiagnosed. A 36-year-old man with a 15-year history of psychosis, seizures, and sensorineural hearing loss and a family history of diabetes mellitus and heart disease presented to our hospital without a unifying diagnosis. Physiologic, biochemical, and genetic testing revealed deficient aerobic metabolism, a defect in mitochondrial electron transport, and the presence of an A-to-G point mutation at position 3243 of the mitochondrial leucine-transfer RNA gene, establishing the diagnosis of mitochondrial encephalopathy, lactic acidosis, and strokelike syndrome (MELAS). Diagnosing mtDNA disorders requires a careful integration of clinical signs and symptoms with pedigree analysis and multidisciplinary testing. Diagnosis is important to provide genetic counseling, avoid unnecessary evaluation, and facilitate therapy for symptomatic relief.

Risperidone-Induced Psychosis and Depression in a Child with a Mitochondrial Disorder

“…There have been published case reports of increased psychiatric and physical difficulties in adults with mitochondrial disorders who were treated with neuroleptics (Kaido et al 1996;Yamazaki et al 1991;Spellberg et al 2001;Iizuka et al 2003). For example, Yamazaki et al report a 37-year-old male with an 8-year history of psychosis and dementia, who later developed hyperpyrexia and dystonia after haloperidol administration.…”

“…Although adult diagnostic criteria have been proposed, childhood diagnostic criteria are not yet formalized (Bernier et al 2002;Skladal et al 2003;Scaglia et al 2004). However, important initial screening tests for mitochondrial disorders include: (1) serum lactate and pyruvate levels, although only 60% of cases with mitochondrial disorder exhibit elevated levels of lactate and serum pyruvate; (2) a nonfasting urinalysis positive for ketones; and (3) serum ammonia, fasting glucose, serum for quantitative amino acids, and urine for quantitative organic acids (Munnich et al 1996;Spellberg et al 2001;Bernier et al 2002;Prietsch et al 2002;Smeitink 2003;Hunter et al 2004;DiMauro et al 2004).…”

Wild-Card Patent Extensions as a Means to Incentivize Research and Development of Antibiotics

“…Spellberg et al write, "However, of all of the potential solutions, transferable patent extensions are generally acknowledged by pharmaceutical companies to be, by far, the incentives most likely to successfully stimulate new antibiotic development." 15 Why are wild-card patent extensions an attractive pull-mechanism for antibiotic R&D from a public health perspective? In addition to not requiring upfront public financing, they are very likely to engage the private pharmaceutical sector in the development of new antibiotics.…”

“…In an article from the spring of 2008, Spellberg et al write, "IDSA currently is not aggressively pursuing adoption of the transferable patent extension concept because of the extreme controversy that has been associated with this idea." 43 There can be little doubt that it is considerations about cost effectiveness, fairness, and moral obligation that has created an air of controversy around the idea. In this paper, I have argued that objections based on these considerations fail, and have therefore indirectly argued that wild-card patent extensions' reputation as being controversial is undeserved.…”

Is a "Mitochondrial Psychiatry" in the Future? A Review

“…Psychotic symptoms such as hallucinations, schizophrenia-like symptoms, schizophrenia, and delirium, in some cases followed by progressive cognitive decline, have been described in case histories of patients with mitochondrial disease with confirmed mtDNA mutations including 3243A>G [23,25,[28][29][30][31][32][33]54], and in mitochondrial disease diagnosed by muscle histochemistry or enzymology (electron transport chain complex activities) [55][56][57][58][59][60][61][62][63].…”