Abstract: Objective To explore the clinical and gene variation characteristics of Imerslund-Gr?sbeck syndrome (IGS) caused by compound heterozygous variation of AMN gene. Methods The clinical data of IGS caused by compound heterozygous mutation of AMN gene in one child were analyzed retrospectively, and the relevant literature was reviewed. Results A ten-yearold boy mainly presented with pale complexion and pallid lips. The hemoglobin of the child was 84 g/L, the red blood cell count was 2 . 44 × 1012 /L, the mean red blood cell volume was 96 . 30 fL, and the mean hemoglobin content was 34 . 4 pg. The blood vitamin B12 concentration was 83 pg/mL. Blood tandem mass spectrometry and urine organic acid analysis suggested methylmalonic acidemia. Pathogenic variants of genes associated with primary methylmalonic acidemia were excluded by genetic screening. Whole exome sequencing revealed that there were compound heterozygous mutations of c.527_530del and c.651+1G>C in AMN gene, and c.651+1G>c was a new variation. The above mutation sites have not been reported. According to the American College of Medical Genetics and Genomics (ACMG) classification, c.527_530del was a likely pathogenic variation, and c.651+1G> c was a pathogenic variation. Combined with the clinical phenotype, IGS was confirmed. The symptoms of methylmalonic acidemia and anemia disappeared after vitamin B12 intramuscular injection. Conclusions Blood tandem mass spectrometry and urine organic acid analysis combined with gene detection, especially total exon sequencing, can improve the diagnostic level of rare genetic metabolic diseases.

Key words: AMN gene; Imerslund-Gr?sbeck syndrome; megaloblastic anemia; methylmalonic acidemia; homocystinemia