Clinical and gene mutation analysis in patients with methylmalonic acidemia and homocystelnemia

Objective Methylmalonic acidemia combined with homocysteinemia is an inborn error of cobalamin metabolism with an autosomal recessive mode. The cb1C type is the most common form of this disease,in which the gene was named MMACHC. This study was aimed to analyse the diagnosis, treatment and gene mutations in 14 patients. Methods Measurements of C3 (propionylcarnitine) , C3/C0 (free carnitine)and C3/C2 (acetylcarnitine) in blood were detected by tandem massepectrometry; urine methylmalonic acid were determined by gas-chromatography mass spectrometry; and serum homosysteine were determined with the method of fluorescence polarization immunization. These patients were treated with vitamin β12, L-carnitine, beta;he, folic acid and vitamin β6. The MMACHC gene was screened by PCR combined with DNA direct sequencing in 14 Chinese patients. Results With treatment clinical symptoms of 12 patients were improved obviously; the levels of blood propionylearnitine and homocysteine as well as urine methylmalonic acid were decreased. Two patients were dead without treatments. In this study, five different mutations in 12 patients were detected, only one polymorphism was found in one patient, and in another patient no mutation was detected. We found 609G>A homozygotic mutations in 7 patients, and heterozygotic ones of 609G > A with 658_660delAAG、567_568insT,394C>T and 217C>T in 5 patients, in which 658_660delAAG and 567_568insT were novel mutations.Conclusion The patients with methylmalonic acidemia and homocysteinemia could have an improved outcome after reasonable treatments. The gene mutation detection suggests that 609G>A (W203X) may be the hot spot mutation of MMACHC gene in Chinese patients. Key words: Methylmalonic acidemia;  Homocysteinemia;  Diagnosis;  Treatment;  Gene mutation