The objective of this study was to investigate clinical, biochemical, and 
genetic features in 7 probands (a total of 11 patients) with nicotine-amide 
adenine dinucleotide (NADH) dehydrogenase (complex I) deficiency. We screened 
the mitochondrial DNA for mutations and found pathogenic mutations in complex I 
genes (mitochondrial NADH dehydrogenase subunit (MTND) genes) in three probands. 
The 10191T>C mutation in MTND3 and the 14487T>C mutation in MTND6 were present 
in two probands with Leigh's-like and Leigh's syndrome, respectively. Four 
siblings with a syndrome consisting of encephalomyopathy with hearing 
impairment, optic nerve atrophy, and cardiac involvement had the 11778G>A 
mutation in MTND4, previously associated with Leber hereditary optic neuropathy. 
These findings demonstrate that mutations in MTND genes are relatively frequent 
in patients with complex I deficiency. Biochemical measurements of respiratory 
chain function in muscle mitochondria showed that all patients had a moderate 
decrease of the mitochondrial adenosine triphosphate production rate. 
Interestingly, the complex I deficiency caused secondary metabolic alterations 
with decreased oxaloacetate-induced inhibition of succinate dehydrogenase 
(complex II) and excretion of Krebs cycle intermediates in the urine. Our 
results thus suggest that altered regulation of metabolism may play an important 
role in the pathogenesis of complex I deficiency.