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This Article Full Text Full Text (PDF) 081166.Supplemental Data All Versions of this Article: clinchem.2006.081166v1 53/5/916    most recent Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Debray, F.-G. Articles by Lambert, M. Search for Related Content PubMed PubMed Citation Articles by Debray, F.-G. Articles by Lambert, M. Related Collections General Clinical Chemistry Pediatric Clinical Chemistry Endocrinology and Metabolism

Diagnostic Accuracy of Blood Lactate-to-Pyruvate Molar Ratio in the Differential Diagnosis of Congenital Lactic Acidosis

Departments of¹ Pediatrics and ² Clinical Biochemistry, Ste-Justine Hospital and Université de Montréal, Montreal, Quebec, Canada.
³ Metabolism Research Programme, Departments of Pediatrics and Biochemistry, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
⁴ Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada.

^aAddress correspondence to this author at: Medical Genetics Service, Ste-Justine Hospital, 3175 Côte-Sainte-Catherine, Montreal, Quebec, H3T 1C5 Canada. Fax 514-345-4766; e-mail marie.lambert{at}umontreal.ca.

Background: Although the blood lactate-to-pyruvate (L:P) molar ratio is used to distinguish between pyruvate dehydrogenase deficiency (PDH-D) and other causes of congenital lactic acidosis (CLA), its diagnostic accuracy for differentiating between these 2 types of CLA has not been evaluated formally.

Methods: We conducted a retrospective study of all patients followed for mitochondrial diseases between 1985 and 2005 in a tertiary care pediatric hospital.

Results: At the recommended cut point of 25, individual median L:P ratio demonstrated low sensitivity and specificity (77% and 91%, respectively) for differentiating between patients with enzymatically proven PDH-D (n = 11) and those with mitochondrial disease but normal pyruvate dehydrogenase (PDH) activity (non-PDH; n = 35). We observed a strong positive association between L:P ratio and blood lactate in non-PDH CLA, whereas this association was weak in PDH-D CLA. Consequently, patient classification based on median L:P ratio showed improved diagnostic accuracy at higher lactate concentrations: for lactate <2.5 mmol/L the area under the ROC curve was not statistically different from 0.5 (P = 0.3), whereas it was statistically different for lactate >2.5 mmol/L. In the 2.5 to 5.0 mmol/L lactate category, the sensitivity and specificity at an optimal cut point of 18.4 were 93% (95% CI, 77%–99%) and 71% (95% CI, 20%–96%), respectively; for lactate >5.0 mmol/L, with an optimal cut point of 25.8, sensitivity and specificity were 96% (95% CI, 77%–99%) and 100% (95% CI, 59%–100%), respectively.

Conclusion: Usefulness of the L:P ratio for differentiating non-PDH and PDH-D types of CLA increases at higher lactate concentrations.