Congenital dyserythropoietic anemia and drug‑induced liver injury present as bland cholestasis: A case report

Abstract

Anemias and drug-induced liver injury(DILI) are separate disorders, which are difficult to diagnose. The clinical effects of DILI vary among individuals. However, the outcome determinants remain to be fully established. To the best of our knowledge, the role of anemia in DILI has yet to be reported. The present study reported on the case of one Chinese patient (male; age, 21 years) who experienced obvious drug-induced cholestasis. Of note, the hepatocyte injury was minimal compared with that in previously reported cases treated with the same drug. In addition, the patient suffered from mild hemolytic anemia with no obvious cause. A genetic pedigree analysis revealed compound heterozygous mutations in the congenital anemia-associated gene codanin 1, including the novel rare p.R1067H mutation. Treatment with ursodeoxycholic acid alone sufficed and the outcome was good. Therefore, whilst chronic hemolysis predisposed the liver to cholestasis, it could have shielded the liver from further injuries, since bilirubin, a by-product of hemolysis, is a known antioxidant. The results of the present study indicated that genetic screening may be used for the diagnosis of liver injury concurring with undiagnosed anemia. Materials and methods Clinical presentation. An otherwise healthy 21-year-old male was initially admitted to Ruijin Hospital (Shanghai, China) in March 2020 due to afebrile painless jaundice for 20 days.

Whole‐exome sequencing for genetic diagnosis of idiopathic liver injury in children

“…Biallelic mutations in CDAN1 have been implicated in congenital dyserythropoietic anaemia type Ia (MIM: 224120), in which affected patients may develop severe hepatic injury such as ALF. 42 , 43 Indeed, the p.Arg649Trp with p.Arg397Trp at compound heterozygosity were reported in a patient with congenital dyserythropoietic anaemia type Ia. 44 However, although this variant was interpreted as likely pathogenic based on the ACMG‐AMP classification (Table 1 ), P5's clinical findings were not compatible with the known phenotypic spectrum of CDAN1 deficiency (Table 2 ).…”

“…Zygosity of p.Arg649Trp was not assessed in P5's parents as their gDNA samples were not available (Figures 1 and S1). Biallelic mutations in CDAN1 have been implicated in congenital dyserythropoietic anaemia type Ia (MIM: 224120), in which affected patients may develop severe hepatic injury such as ALF 42,43 . Indeed, the p.Arg649Trp with p.Arg397Trp at compound heterozygosity were reported in a patient with congenital dyserythropoietic anaemia type Ia 44 .…”