A NEW MITOCHONDRIAL-DNA DELETION ASSOCIATED WITH DIABETIC AMYOTROPHY,DIABETIC MYOATROPHY AND DIABETIC FATTY LIVER

Mitochondrial dysfunctions of the muscle in diabetic amyotrophy and of the liver in diabetic fatty liver have been reported. We investigated mitochondrial gene mutations in three cases: (1) a patient with diabe tic amyotrophy in the muscles of the lower extremities, and neuropathy ; (2) 5 diabetics with myoatrophy, diabetic nephropathy, and chronic r enal failure; and (3) an IDDM patient with a diabetic fatty liver. We identified a 5778-69 deletion (8214-13991) in mitochondrial DNA from t he muscle and liver biopsy specimens by the primer shift PCR and PCR-d irect sequence methods. It is speculated that 5778-bp deletion is due to homogeneous recombination in the 7-bp repeat sequence of TCCTAGA fl anking the region deleted in the mitochondrial DNA. Determination of r espiratory chain enzyme activities in fresh muscle mitochondria demons trated the defect in complex I activity, The deletion covers areas cod ing ND3, ND4, ND4L, and ND5 in complex I. The 5778-bp deletion might c ause a defect in mitochondrial oxidative phosphorylation and contribut e to the pathogenesis of diabetic amyotrophy, myoatrophy with diabetic nephropathy, and chronic renal failure, as well as diabetic fatty liv er in IDDM. (C) 1995 John Wiley and Sons, Inc.