To explore the clinical features, diagnosis, treatment and prognosis of twins boys with secondary methylmalonic aciduria (MMA) due to maternal vitamin B₁₂ deficiency.

On November 12, 2014, the twins boys in 27 days old with secondary MMA due to maternal vitamin B₁₂ deficiency in Peking University First Hospital were selected as research objects. The chief complaint was" vomiting milk and anemia, suspected diagnosis of inherited MMA" . Routine blood, serum vitamin B₁₂ and folic acid test, serum and urine total homocysteine detection, urine organic acids spectrum, blood amino acids and carnitine spectrum detection of the two twins patients and their mother were applied for the differential diagnosis. Meanwhile, mutations in MMA related gene of the two twins patients and their parents were detected. The twins patients′ parents signed the informed consents and this study was approved by the Ethical Review Board of Investigation in Human Being of Peking University First Hospital.

①In 4 days old, the urine methylmalonic acid concentrations of 2 cases of twins boys were 479.21 mmol/mol creatinine and 65.90 mmol/mol creatinine, respectively (normal reference value was 0.20-3.60 mmol/mol creatinine), and the concentrations of blood propionyl-carnitine were 12.01 μmol/L and 10.55 μmol/L, respectively (normal reference value was 1.00-5.00 μmol/L) in the local hospital. Both the twins boys were with moderate anemia when they visited Peking University First Hospital in 27 days old. And serum homocystine concentration in the elder boy was mild elevated which was 17.6 μmol/L (normal reference value was 0-15.0 μmol/L), while serum homocystine concentration in the younger boy was normal which was 14.3 μmol/L. Both the serum vitamin B₁₂ concentrations decreased which were 121.0 pmol/L and 105.0 pmol/L, respectively (normal reference value was 133.0-675.0 pmol/L). Both the serum folic acid concentrations were normal which were 26.5 nmol/L and 18.60 nmol/L, respectively (normal reference value was >6.80 nmol/L). Methylmalonic acid was not detected in their urine, and concentrations of blood propionyl-carnitine increased which were 9.26 μmol/L and 15.90 μmol/L, respectively. Vitamin B₁₂ intramuscular injection, normal diet with the supplements of calcium folinate and levocarnitine by oral had been initialed. After two months of treatment, urine methylmalonic acid was not found and blood propionyl-carnitine concentrations decreased to normal. And the twins were with normal intelligence and motor development. The anemia were improved. ②The mother of the twins manifested morning sickness with pregnancy anorexia and emesis. She had diabetes, hypothyroidism, megaloblastic anemia and homocysteinemia at mid trimester of pregnancy. Although she had taken some traditional Chinese medicine and chalybeate, vitamin B₁₂ was not supplemented. Vitamin B₁₂ deficiency and homocysteinemia were found two months postpartum. After the treatment of levocarnitine, mecobalamin and folic acid, her serum vitamin B₁₂ and homocystine concentrations returned normal four months postpartum. ③Gene analysis of associated inherited MMA revealed that MUT, MMAA, MMAB, MMACHC gene mutation were no found in the twins and their parents.

Prenatal malnutrition and poor health in the mother could lead to the deficiency of vitamin B_12,which in turn cause baby′s secondary MMA. Early differential diagnosis of inherited or secondary MMA and vitamin B₁₂ supplements in time are crucial to treat and improve the prognosis of secondary MMA. For the pregnant woman with anemia, vitamin B₁₂ deficiency should be paid attention, in order to avoid second MMA in infants.