Clinical analysis of two brothers with Imerslund-Gräsbeck syndrome

Abstract

The clinical data of two children with Imerslund-Gräsbeck syndrome (IGS) who were admitted to the First Affiliated Hospital of Zhengzhou University in August 2019 was analyzed retrospectively. The two cases were siblings, aged 8 years and 8 months and 6 years and 2 months, respectively. These two boys had megaloblastic anemia, low level of vitamin B12, hyperhomocysteinemia, accompanied by proteinuria and renal tubular injury, while they showed normal folate level and renal function. Blood tandem mass spectrometry and urine organic acid analysis suggested methylmalonic acidemia (MMA). The initial diagnosis was MMA with homocysteinemia. No known pathogenic gene mutation related to MMA was found by gene sequencing. Compound heterozygous variants of amnionless (AMN) gene were detected: c.43+5G>A and c.C717G. The corrected diagnosis was IGS. Both brothers were treated with long-term intramuscular injection of vitamin B12. After follow-up for one year, these two cases had no clinical symptoms, and their blood indicators remained normal, but proteinuria and renal tubular injury persisted. Blood tandem mass spectrometry and urine organic acid analysis alone may easily lead to misdiagnosis, but combined with genetic testing can improve the accuracy of diagnosis of IGS. Lifelong parenteral vitamin B12 replacement therapy can effectively reverse the clinical and biochemical results, but is uncertain in alleviating albuminuria and renal tubule injury. It's necessary to monitor the renal function regularly.