Published online Sep 21, 2018. doi: 10.3748/wjg.v24.i35.4086
Peer-review started: June 7, 2018
First decision: June 20, 2018
Revised: July 17, 2018
Accepted: August 1, 2018
Article in press: August 1, 2018
Published online: September 21, 2018
Steroid 5β-reductase [aldo-keto reductase family 1 member D1 (AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307 (p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid (UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid (CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.
Core tip: We report a case of an infant with primary 3-oxo-Δ4-steroid 5β-reductase deficiency with a novel missense mutation in the aldo-keto reductase family 1 member D1 (AKR1D1) gene. The patient was successfully treated by early adequate supplementation with chenodeoxycholic acid (CDCA). This case suggests that a novel compound heterozygous R307C mutation and loss of heterozygosity in the AKR1D1 gene play a pathogenic role in congenital bile acid synthesis defect type 2. Accurate diagnosis of the disease and early adequate supplementation with CDCA are vital for the amelioration of symptoms in clinical practice.