Abstract Details

Title Life-Threatening Lactic Acidosis Occuring in Adults with Rare Mutations of mtDNA: About Three Cases

Topic Muscle Disease/Neuromuscular Junction

Presentation(s) P07 - (-)

Poster/Presentation
Number 022

Objective

Background BACKGROUND: Acute metabolic crisis are often encountered in childhood- onset mitochondrial diseases (MD), whereas adults generally present with progressive neurological or muscle involvement.

Design/Methods DESIGN/METHODS: Investigations included blood analysis, EMG, and muscle biopsy for histoenzymological and respiratory chain analysis. Mitochondrial DNA analysis was performed in muscle, blood, buccal cells, and urine.

Results RESULTS: Patients were one woman and two men, aged 27, 32 and 32 years. They presented with slowly progressive muscle weakness and fatigability, compatible with a normal life, several years before the acute metabolic crisis. Two patients experienced prodromal abdominal pain and vomiting; all of them developed acute respiratory failure and collapse needing mechanical ventilation. Concomitant status epilepticus occurred in one patient. Lactic acidosis was present in all cases (20, 24 and 30 mM) necessitating extra-renal dialysis. Hepatic cytolysis was constant, contrasting with moderately increased CK levels (3N to 5N). No triggering factor could be identified. All patients fully recovered after prolonged intensive care, but resting lactate levels constantly remained elevated up to 8 mM. Muscle biopsy showed numerous ragged-red and COX-negative fibers in two patients, and lipidosis in the third one. Combined deficiency of mtDNA-dependant respiratory complexes was not explained by mtDNA depletion or deletion. Heteroplasmic pathogenic point mutations were detected in tRNA genes: MT-TL1 (m.3280G>A; m.3258C>T) and MT-TK (m8363A>G). Tissue distribution was heterogeneous for the MT-TL1 mutations but homogeneous for the MT-TK mutation (as observed with recurrent MELAS and MERRF mutations).

Conclusions CONCLUSIONS: Life-threatening lactic acidosis may be inaugural or a major clinical manifestation in adults with mtDNA mutations. Prolonged intensive care may obtain dramatic and sustained improvement.

Authors/Disclosures
Corinne Dupel Pottier, MD (CH Rene Dubos) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Bruno Eymard, MD	No disclosure on file
Edward Fox, MD, PhD, FAAN	Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GW Pharmaceuticals. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Fox has received research support from Biogen. The institution of Dr. Fox has received research support from Genentech. The institution of Dr. Fox has received research support from Celgene - BMS. The institution of Dr. Fox has received research support from Chugai. The institution of Dr. Fox has received research support from Novartis. The institution of Dr. Fox has received research support from EMD-Serono. The institution of Dr. Fox has received research support from TG Therapeutics. The institution of Dr. Fox has received research support from AbbVie. The institution of Dr. Fox has received research support from Sanofi Genzyme. The institution of Dr. Fox has received research support from AbbVie.
	No disclosure on file
	No disclosure on file
Pascal Laforet (Hopital Pitie Salpetriere)	No disclosure on file

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