Abstract: 　Objective　To analyze the clinical and genetic characteristics of critical methylmalonic academia. Methods The clinical data of 34 cases of critically methylmalonic acidemia from September 2015 to December 2018 were retrospectively analyzed, among which 11 cases underwent genetic testing. Results　In the 34 cases (18 males and 16 females) median age was 11.5 months. All the children had 2 or more organ dysfunction or failure. In addition to the damages commonly seen in blood system, liver, kidney, heart, pulmonary vascular and nervous system, 11 patients had decreased fibrinogen level and 3 patients had congenital atresia of the middle and lateral foramen of the fourth ventricle (Dandy-Walker malformation). In the 11 children who underwent genetic testing, 9 had mutations in MMACHC gene, and c.609G>A mutation was a hot spot mutation in combined methylmalonic acidemia. Two children with brain developmental malformation had mutations of c.609G>A. The other 2 cases were simple methylmalonic acidemia, both caused by the mutation in methylmalonyl coenzyme A mutase (MUT) gene. Conclusions　Neurological damage is most common in children with critical methylmalonic acidemia, and some children may be associated with brain developmental malformations, which may be related to c.609G>A locus mutation. The level of fibrinogen can be decreased.

Key words: 　methylmalonic acidemia;　fibrinogen;　Dandy-Walker malformation