Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency in Zhejiang province, China

3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD) is an autosomal recessive inborn defect of leucine catabolism caused by MCCC1 or MCCC2 variants. 3-MCCD is considered to be a relatively benign disorder with favorable outcome. We report the biochemical, clinical, and molecular features of patients with 3-MCCD. From January 2009 to August 2022, 4,402,587 newborns were screened by tandem mass spectrometry. Newborns with increased C5OH concentrations were recalled for repeated testing, urine organic acid analysis and molecular genetic analysis were performed if the second test was still positive. A total of 53 patients were diagnosed with 3-MCCD. The estimated incidence of 3-MCCD in Zhejiang Province was 1 in 83,068 newborns. All these 53 patients exhibited increased C5OH concentrations in blood. 94 % (50/53) of the patients had markedly increased urinary 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. All these 53 patients did not present any clinical symptom. Twenty-three of 53 patients had secondary carnitine deficiency. Twenty-eight patients had variants in MCCC1 and 25 had variants in MCCC2. Eleven novel variants were found in MCCC1 and MCCC2. The c.639 + 2 T > A and c.1144-1147delinsTTTT were the most common variant in MCCC1 and MCCC2 gene, respectively. We elucidated the incidence of 3-MCCD in Zhejiang province, China. All patients showed asymptomatic and present normal growth and development during follow-up. Eleven novel MCCC1 and MCCC2 variants were identified, which expanded the variant spectrum.