To investigate the clinical characteristics of methylmalonic acidemia (MMA) and review the related literatures, aiming at improving the clinicians′ recognition of MMA.

On November 2, 2016 and February 25, 2017, two children with MMA who were misdiagnosed as hematological diseases were selected as research subjects. The clinical data of this 2 children were collected from Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University. Their ages were 5-month and 15-year old, respectively. A retrospective analysis of the diagnosis and treatment processes of the 2 children with MMA was conducted, and a search strategy was set. The key words were " methylmalonic academia" " misdiagnosis" " blood routine" and " MMA" . Literatures on MMA were searched in Wanfang Database, China National Knowledge Infrastructure (CNKI) Database, etc.. The retrieval period was from January 1, 2000 to December 31, 2017. The genetic metabolic disease gene Panel sequencing based on high-throughput sequencing technology was used to analyze the mutation of the pathogenic gene. This study met the requirements of the World Medical Association Declaration of Helsinki revised in 2013.

①Case 1 was misdiagnosed as small cell hypochromic anemia at 1 month old, and she was diagnosed as MMA at 5 months old. The results of high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) showed that propionylcarnitine (C3) was 3.2 μmoL/L, C3/ acetylcarnitine (C2) was 0.34, C3/free carnitine (C0) was 0.22. The results of urine gas chromatography-mass spectrometry (GC/MS) showed that the urine methylmalonic acid value was 20 μg/μmoL creatinine. The concentration of serum homocysteine (Hcy) was 40 μmol/L. Blood routine examination showed hemoglobin (Hb) was 105 g/L. The results of gene detection indicated that the mutation site of the gene was MMACHC c. 80G>A/c.609G>A. This girl was finally diagnosed as MMA complicated with hyperhomocysteinemia, belonging to cblC type. ② Case 2 was misdiagnosed as thrombocytopenia at 6 months old, and this boy was diagnosed as MMA at the age of 15. HPLC-MS/MS results showed that C3 was 7.22 μmo/L, C3/C2 was 0.32, C3/C0 was 0.82. Urine GC/MS results showed that urine methylmalonic acid was 14.02 μg/μmoL creatinine. Serum Hcy concentration was 80 μmol/L. Blood routine examination showed that Hb was 103 g/L and platelet count was 85×10⁹/L. The results of gene detection indicated that mutation site of the gene was MMACHC c. 482G>A/c.609G>A. This boy was finally diagnosed as MMA complicated with hyperhomocysteinemia, belonging to cblC type. ③The two children were misdiagnosed as hematological diseases and received treatment such as blood transfusion, iron treatment and hormone administration, etc., with no obvious clinical effects. After two children were diagnosed with MMA, they were given intramuscular injection of hydroxycobalamin (1 mg/d) and oral administration of L-carnitine, betaine and calcium folinate for 1 month. The results of blood routine examination showed that all indexes were within the normal reference range and the condition was stable.

The clinical manifestations of MMA are nonspecific, and some children are easily misdiagnosed as blood system diseases. Blood HPLC-MS/MS, urine GC/MS and gene detection are effective methods for diagnosing MMA.