Clinical characteristics, plasma levels of hydrogen sulfide and gene analysis of cardiovascular involvement in children with methylmalonic acidemia and homocystinemia / 中华实用儿科临床杂志

ABSTRACT

Objective:To explore the clinical characteristics, plasma levels of hydrogen sulfide(H 2S) and the relationship between the genotype and phenotype of cardiovascular involvement in children with methylmalonic acidemia and homocystinemia. Methods:The clinical and laboratory data of 66 outpatients diagnosed with methylmalonic acidemia combined with homocystinemia in Department of Pediatrics, Peking University First Hospital from January 2014 to July 2014 were collected and analyzed respectively, and the patients were divided into 2 groups cardiovascular involvement group (10 cases) and non-cardiovascular involvement group(56 cases). The differences in the clinical characteristics, plasma levels of H 2S and genotypes were compared between 2 groups. Results:(1) There were 45 cases of early-onset children under 1 year old, including 4 cases of cardiovascular system involvement and 41 cases of non-cardiovascular system involvement.Twenty-one cases had onset above 1 year old, including 6 cases of cardiovascular system involvement and 15 cases of non-cardiovascular system involvement. There were 44 male children, including 8 cases with cardiovascular system involvement and 36 cases without cardiovascular system involvement; 22 cases female children, including 2 cases with cardiovascular system involvement and 20 cases without cardiovascular system involvement. There was no significant difference in onset age and gender distribution between the 2 groups ( χ2=2.910, 0.368, all P>0.05). (2)In the 10 cases with cardiovascular involvement, there were 3 cases with hypertension, 2 cases with hypertension combined with pulmonary hypertension, 2 cases with mild myocardial hypertrophy, 1 case with atrial septal defect combined with pulmonary hypertension, 1 case with pulmonary hypertension, 1 case with myocardial noncompaction.Compared with the non-cardiovascular involvement group, the proportion of kidney involvement was increased and that of nervous system was decreased in cardiovascular system involvement group( χ2=20.34, 5.79, all P<0.05), the proportion of hematological system involvement between the 2 groups had no significant differences ( χ2=1.28, P>0.05). The plasma levels of hydrogen sulfide of children with cardiovascular involvement was significantly lower than that of non-cardiovascular involvement[(33.8±3.6) μmol/L vs.(39.3±5.2) μmol/L, t=-3.22, P<0.01]. (3) MMACHC gene mutation (cblC type) was identified in all 46 patients.It was found that the most common type of gene mutation was c. 80A>G in cardiovascular involvement group, while c. 609G>A was the most common type of gene mutation in non-cardiovascular involvement group. Conclusions:The clinical manifestations of children with methylmalonic acidemia and homocystinemia involving cardiovascular system are multiple and prone to multiple system involvement, especially renal involvement.A decrease in plasma hydrogen sulfide levels may be involved in the involvement of its cardiovascular system.The MMACHC gene c. 80A>G mutation is the most common genetic mutation site in children with cardiovascular involvement with methylmalonic acidemia and homocystinemia.