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

Δ4-3-Oxosteroid 5ß-reductase (AKR1D1) deficiency typically causes severe cholestasis occurs in newborns, leading to death unless patients are treated with primary bile acids. However, we encountered an AKR1D1 deficiency patient treated with only ursodeoxycholic acid who had cholestasis until about 1 year of age but then grew up healthy without further treatment. We also have been following other healthy patients with AKR1D1 mutation who have never developed cholestasis and have not been treated. However, reports are few, involving 3 patients. To better understand and clinically manage a diverse group of patients with AKR1D1 mutation who do not develop potentially fatal cholestasis in the neonatal period, ongoing accumulation and study of informative cases is needed.

Clinical and genetic features of congenital bile acid synthesis defect with a novel mutation in AKR1D1 gene sequencing: Case reports.

RATIONALE: Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5ß-reductase enzyme. Early disease diagnosis is critical for early treatment with bile acid replacement therapy, with an excellent chance for recovery. In contrast, protracted diagnosis and treatment may lead to poor outcomes, including decompensated hepatic cirrhosis, liver transplant, and even death. PATIENT CONCERNS: Three clinical congenital bile acid synthesis defect cases in the Vietnamese population are herein reported. These pediatric patients presented with symptoms of prolonged postpartum jaundice and abnormal loose stool (mucus, lipids, and white). The clinical examinations showed hepatosplenomegaly. Urinalysis showed a very low fraction of primary bile acids and atypical 3-oxo-Δ4- bile acids in all three patients. DIAGNOSES: The patients were diagnosed with primary Δ4-3-oxosteroid 5ß-reductase deficiency. Next-generation gene sequencing revealed two homozygous mutations in the aldo-keto reductase family 1 member D1 gene. The first is a documented variant, c.797G>A (p.Arg266Gln), and the second is a novel mutation at c.155T>C (p.Ile52Thr). INTERVENTIONS: Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d. OUTCOMES: The patients' symptoms, signs, and primary bile acids levels improved significantly. LESSONS: Clinicians should consider genetic disorders related to cholestasis for effective and life-saving treatment. A prompt genetic analysis by next-generation gene sequencing enables patients to access bile acid replacement therapy earlier, significantly improving short- and long-term outcomes.