[Application of tandem mass spectrometry in diagnosis of organic acidemias]

Abstract

Objective: The diagnosis of organic acidemia is very difficult and needs special test methods. Recently the tandem mass spectrometry has been used in screening for and diagnosis of this inborn error of metabolism. The aim of the present study was to utilize a dry blood filter paper method for acylcarnitines profiles test using tandem mass spectrometry in diagnosis of organic acidemias in high risk children.

Method: One thousand patients (642 were males and 358 females) with high risk of inborn error of metabolism were studied, the median of their age was 2 years. The blood specimens were collected on filter paper, punched and extracted into methanol solution with stable isotope labeled internal standards of acylcarnitine, then derivatized with butanolic-HCI. After preparation, the samples were analyzed by tandem mass spectrometry. The volume of the acylcarnitines was calculated with special software.

Results: Forty patients (4.0%) were diagnosed as organic acidemias among the 1000 patients, including 20 methylmalonic acidemia, 6 propionic acidemia, 3 isovaleric acidemia, 3 glutaric acidemia type I, 3 glutaric acidemia type II, 2 biotinidas deficiency, 1 3-methylcrotonyl-CoA carboxylase deficiency, 1 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, and 1 beta-keto thiolase deficiency. The common clinical symptoms and signs of these patients were motor and mental developmental retardation, spasm, lethargy, coma, hypotonia, vomiting, and feeding difficulty. Routine laboratory tests suggested metabolic acidosis, hyperammonemia, hyperlactacidemia, hypoglycemia, anemia, and abnormal liver function.

Conclusion: A part of organic acidemias can be rapidly diagnosed by tandem mass spectrometry through acylcarnitine profiles analysis in dry blood filter paper. Combination of tandem mass spectrometry with urine gas chromatography mass spectrometry would improve more accurate diagnosis of organic acidemias.