[A pilot study of selective screening for high risk children with inborn error of metabolism using tandem mass spectrometry in China].

OBJECTIVE: The new technology of tandem mass spectrometry is exerting a significant impact on the diagnostics of inborn metabolic errors, and allows to detect a number of these disorders in a single step. The aim of the present study was to establish a dry blood filter paper method for amino acid and acylcarnitine profiles test using tandem mass spectrometry and to apply the method for selective screening in high risk children with inborn error of metabolism.

METHOD: The study group consisted of 104 high risk cases of inborn error of metabolism from 5 pediatric hospitals in Shanghai and Beijing were tested from November 2002 to June 2003; 77 were males and 27 females, the means age was 4.8 +/- 4.2 years. These patients had mental retardation, slow development, psychological abnormalities, muscle hypotonia, jaundice, hepatosplenomegaly, recurrent vomiting, and convulsion. Laboratory examinations suggested metabolic acidosis, hypoglycemia, hyperammonemia and hyperlactacidemia. Phenylketonuria was excluded in this study by routine phenylalanine screening. The control group consisted of 308 children, 170 males and 138 females. The blood was collected on filter paper, punched and extracted into methanol solution with stable isotope labeled internal standards, then derivatized with butanolic-HCl. After preparation, the samples were analyzed by tandem mass spectrometry (API 2000).

RESULTS: Ten of 104 patients (9.6%) were positive in our selective screening program, including one with tyrosinemia, one with homocystinuria, one with hyperornithinemia, two with methylmalonic acidemia, one with propionic acidemia, one with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, two with medium chain acyl-CoA dehydrogenase deficiency, and one with carnitine palmitoyl transferase type II deficiency.

CONCLUSION: The authors established a fast, accurate and sensitive tandem mass spectrometry method for amino acid and acylcarnitine profiles analysis, nearly 30 metabolic diseases including amino acid disorders, organic acid disorders and fatty acid oxidation disorders could be detected, most of the diseases that cause death and disability represent preventable entities by early diagnosis and treatment. The results indicated the importance of selective screening for high risk patients with inborn error of metabolism.