Hereditary spherocytosis coexisting with UDP-glucuronosyltransferase deficiency highly suggestive of Crigler-Najjar syndrome type II

Abstract

Patients with co-existing hereditary spherocytosis (HS) and UDP-glucuronosyltransferase 1A1 (UGT1A1) deficiency as Gilbert's syndrome (GS) have been reported, and previous studies have demonstrated an increased risk for developing gallstones in patients with co-inheritance of GS and HS. We experienced an interesting case of HS showing persistent jaundice after splenectomy, and upon further evaluation, the 25-year-old female patient was found to have HS combined with UGT1A1 deficiency. Sequence analysis of the UGT1A1 gene revealed that she was a compound heterozygote with p.[G71R; Y486D] + [Y486D] mutations, which suggests Crigler-Najjar syndrome type II rather than GS. Careful evaluation of inappropriately elevated bilirubin level compared with the degree of hemolysis is important, reflecting the therapeutic implication of splenectomy and cholecystectomy.

Fig. 1

Nucleotide sequences of the mutated sections of exons 1 and 5 and the promoter region of the gene encoding UDP-glucurono-syltransferase 1A1 (UGT1A1). (A) Nucleotide sequences of the mutated section of exon 1 of the UGT1A1 gene. A missense mutation at nucleotide 211 in exon 1 of the UGT1A1 gene is observed. The substitution of adenine for guanine changed the codon from GGA to AGA, causing arginine to replace glycine at position 71 (p.G71R in the corresponding protein). An arrow shows the mutation. The patient was heterozygous for p.G71R. (B) Nucleotide sequence of the mutated section of exon 5 of the UGT1A1 gene. The arrow shows the mutation. The patient was homozygous for a point mutation at base position 1456 in exon 5. The substitution of guanine for thymine changed the codon from TAC to GAC, causing a tyrosine-to-aspartic acid substitution at position 486 (p.Y486D in the corresponding protein).