[en] Two siblings presented with encephalopathy, lactic acidosis, and hypocitrullinemia. Muscle and liver biopsies were considered for respiratory chain studies, but because of hypocitrullinemia, molecular analysis for maternally inherited Leigh syndrome was first performed, revealing in both siblings the mitochondrial DNA T8993G mutation (95% heteroplasmy), allowing to avoid tissue biopsies. Hypocitrullinemia, an occasional finding in mitochondrial diseases, has been specifically associated with T8993G mutation. However, only few patients have been reported, and the prevalence of hypocitrullinemia in 8993 mitochondrial DNA mutations is unknown. In a small series of 16 Leigh syndrome patients, sensitivity and specificity of hypocitrullinemia (< or = 12 micromol/L) for 8993 mitochondrial DNA mutations were 66% and 85%, respectively. Although studies in larger cohorts are necessary, we suggest considering T8993G mutation early in the diagnostic evaluation of infantile mitochondrial diseases with hypocitrullinemia, which minimizes the need for invasive procedures associated with a small but nonnegligible risk of complications and incorrect diagnosis.
Debray FG, Lambert M., Lortie A., et al. Long-term outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation. Am J Med Genet. 2007 ; 143A: 2046-2051.
Parfait P., de Lonlay P., von Kleist-Retzow JC, et al. The neurogenic weakness, ataxia and retinitis pigmentosa (NARP) syndrome mtDNA mutation (T8993G) triggers muscle ATPase deficiency and hypocitrullinaemia. Eur J Pediatr. 1999 ; 158: 55-58.
Rabier D., Diry C., Rötig A., et al. Persistent hypocitrullinaemia as a marker for mtDNA NARP T8993G mutation ? J Inher Metab Dis. 1998 ; 21: 216-219.
Ribes A., Riudor E., Valcarel R., et al. Pearson syndrome: altered tricarboxylic and urea cycle metabolites, adrenal insufficiency and corneal opacities. J Inher Metab Dis. 1993 ; 16: 537-540.
Naini A., Kaufmann P., Shanske S., et al. Hypocitrullinemia in patients with MELAS: an insight into the "MELAS paradox. J Neurol Sci. 2005 ; 229: 187-193.
Vazquez-Memije ME, Shankse S., Santorelli FM, et al. Comparative biochemical studies of ATPase in cells from patients with the T8993G or T8993C mitochondrial DNA mutation. J Inher Metab Dis. 1998 ; 21: 829-836.
Rahman S., Blok RB, Dahl HHM, et al. Leigh syndrome: clinical features and biochemical and DNA abnormalities. Ann Neurol. 1996 ; 39: 343-351.
Santorelli FM, Shanske S., Macaya A., et al. The mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh syndrome. Ann Neurol. 1999 ; 34: 827-834.
White SL, Shanske S., McGill JJ, et al. Mitochondrial DNA mutations at nucleotide 8993 show a lack of tissue-or age-related variation. J Inher Metab Dis. 1999 ; 22: 899-914.