Endocrine disorders in two sisters affected by MELAS syndrome

A variety of endocrine and metabolic defects, including hypothalamopituitary hypofunction and diabetes mellitus, has been reported in association with mitochondrial disorders. We describe two sisters affected by mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) syndrome in whom DNA analysis showed an A-->G transition at the 3243rd nucleotide position on the transfer RNALeu(UUR) gene with 65% and 45% of mutant-type mitochondrial DNA present in the blood cells of the younger and the older sister, respectively. The younger sister had severe involvement of the central nervous system with mental retardation, epilepsia partialis continua, and strokelike episodes. Endocrine investigations showed an extensive neuroendocrine dysfunction with growth hormone deficiency, hypothalamopituitary hypothyroidism, prepubertal gonadotropin levels, and absence of any secondary sexual characteristics at the age of 12 6/12 years. The neurologically normal older sister was affected by diabetes mellitus and had normal hypothalamopituitary function. Our report confirms that the endocrine system can be affected differently by the same mitochondrial DNA mutation, depending on the heteroplasmia phenomenon. A complete endocrine evaluation must be performed in patients affected by mitochondrial disease and the existence of a mitochondrial disorder should be taken into account in patients with endocrine abnormalities, even if neuromuscular signs are lacking.