Healthy Patients With AKR1D1 Mutation Not Requiring Primary Bile Acid Therapy: A Case Series

Area of Science:

• Biochemistry and Genetics
• Pediatric Gastroenterology and Hepatology

Background:

• Delta4-3-Oxosteroid 5beta-reductase (AKR1D1) deficiency is typically associated with severe neonatal cholestasis, often fatal without primary bile acid treatment.
• Existing literature on non-fatal AKR1D1 deficiency cases is limited, with only three patients previously reported.

Purpose of the Study:

• To describe and analyze cases of AKR1D1 deficiency that do not present with severe neonatal cholestasis.
• To improve the clinical understanding and management of diverse AKR1D1 deficiency patient phenotypes.

Main Methods:

• Clinical case observation and follow-up of patients with AKR1D1 mutations.
• Review of existing literature on AKR1D1 deficiency.

Main Results:

• A case of AKR1D1 deficiency treated with ursodeoxycholic acid showed cholestasis resolving by one year of age, with subsequent healthy development.
• Other AKR1D1 mutation patients have been identified who never developed cholestasis and required no treatment.
• These findings expand the known spectrum of AKR1D1 deficiency beyond severe neonatal cholestasis.

Conclusions:

• AKR1D1 deficiency exhibits a broader clinical spectrum than previously recognized, including milder or absent cholestasis.
• Further accumulation and study of informative cases are crucial for understanding and managing non-fatal AKR1D1 deficiency phenotypes.
• This research underscores the importance of individualized assessment in managing genetic metabolic disorders.