Objectives: To investigate the values of tandem mass spectrometry (MS/MS) in etiologic diagnosis and understanding therapeutic effect in cerebral developmental retardation, and to help patients in early diagnosis, treatment and favorable prognosis.
Methods: One hundred and fifty-eight childhood patients with brain heteroplasia were tested from July 2004 to October 2006. 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 analysed by tandem mass spectrometry. Eleven MS/MS-positive patients were further analyzed based on gas chromatography/mass spectrometry (GC/MS) analysis of urine, clinical course, and treatment outcome.
Results: Eleven of 158 patients (7.0%) with inborn metabolic error were confirmed, including five with methylmalonic acidemia, two with propionic acidemia, one with ornithine transcarbamylase deficiency, one with maple syrup urine disease, one with phenylketonuria, and one with biotinidase deficiency. Among them, five were male, six were female, aged from 4 days to 21 months. The clinical manifestations were diverse, including mental developmental retardation or degradation (11 cases), convulsion (5 cases), coma (4 cases), vomiting (4 cases), malnutrition (4 cases), lethargy (3 cases), repeated infection (3 cases), hypotonia (2 cases), etc. Laboratory findings showed metabolic acidosis, hyperammonemia, hyperlactacidemia, anemia, etc. MRI findings of the brain showed cerebral atrophy, a pattern of bilateral T(2)W high signal intensity or/and T(1)W low signal intensity in cerebral white matter and multiple encephalomalacia or vesicular change, ect. In methylmalonic acidemia patients, the early onset with severe acidosis and coma have had a poor prognosis. Improvement was observed in 8 cases after treatment with vitamin B(12), L-carnitine, special milk, low-protein diet or biotin, etc. However 3 MMA patients died.
Conclusion: MS/MS was helpful for some patients in etiologic diagnosis and understanding therapeutic effect of cerebral developmental retardation. Early diagnosis and appropriate treatment are essential to improve the prognosis and prevent brain damage.