ABSTRACT
DNA and how many abnormal mitochondria are in a given tissue
(heteroplasmy). l Classical phenotypes may only be partially expressed (oligosymptomatic). l Mitochondrial disorders are frequently maternally inherited and involve a
large number of mutations. l The disorder MELAS, refers to mitochondrial encephalopathy, lactic
acidosis, and stroke-like episodes, is one of the classical phenotypes that
has been extensively described (most common mutation is an A-G tran-
sition mutation at position 3243 of the mitochondrial genome). l Manifestations of MELAS are seizures, encephalopathy, stroke-like epi-
sodes, short stature, cognitive dysfunction, migraine headaches, depres-
sion, hearing loss, cardiomyopathy and cardiac conduction deficits,
myopathy, and neuropathy. l Type 2 diabetes mellitus is identified in 33%; some cohorts have had
diabetes in all carriers by age 70. l Avoid use of metformin because of the risk of lactic acidosis in these
patients. l Peripheral neuropathy is present in 22% of these cases and may be
mistaken for diabetic polyneuropathy. l Consider mitochondrial disease in the presence of a strong, matrilineal
clustering of diabetes, presence of short stature, and hearing loss. l Gastrointestinal manifestations may be prominent and erroneously attributed
to diabetic autonomic neuropathy-constipation, gastric discomfort, others. l Other mitochondrial syndromes (uncommon): MERRF (myoclonic epilepsy
with ragged red fibers), Pearson syndrome, Wolfram syndrome (see earlier),
Leigh disease, CPEO (chronic progressive external ophthalmoplegia), NARP
(neuropathy, ataxia, and retinitis pigmentosa), and LHON (Leber hereditary
optic neuropathy), CADN (cerebellar ataxia, deafness, and narcolepsy),
Feigenbaum syndrome (cognitive dysfunction, deafness, atherosclerosis,
other deficits). l References (128,129).
