Original Article

Journal of Inherited Metabolic Disease

, Volume 36, Issue 3, pp 565-573

Two neonatal cholestasis patients with mutations in the SRD5B1 (AKR1D1) gene: diagnosis and bile acid profiles during chenodeoxycholic acid treatment

  • Yoshitaka SekiAffiliated withDepartment of Pediatrics and Child Health, Kurume University School of Medicine
  • , Tatsuki MizuochiAffiliated withDepartment of Pediatrics and Child Health, Kurume University School of Medicine
  • , Akihiko KimuraAffiliated withDepartment of Pediatrics and Child Health, Kurume University School of Medicine Email author 
  • , Tomoyuki TakahashiAffiliated withDepartment of Pediatrics and Child Health, Kurume University School of MedicineDivision of Gene Therapy and Regenerative Medicine, Cognitive and Molecular Research Institute of Brain Disease, Kurume University
  • , Akira OhtakeAffiliated withDepartment of Pediatrics, Faculty of Medicine, Saitama Medical University
  • , Shin-Ichi HayashiAffiliated withDepartment of Pediatric Surgery, Faculty of Medicine, Saitama Medical University
  • , Toshiya MorimuraAffiliated withDepartment of Pediatric Surgery, Faculty of Medicine, Saitama Medical University
  • , Yasuharu OhnoAffiliated withDepartment of Pediatric Surgery, Faculty of Medicine, Saitama Medical University
  • , Takayuki HoshinaAffiliated withDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University
    • , Kenji IharaAffiliated withDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University
    • , Hajime TakeiAffiliated withInstitution of Bile Acid, Junshin Clinic
    • , Hiroshi NittonoAffiliated withInstitution of Bile Acid, Junshin Clinic
    • , Takao KurosawaAffiliated withFaculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido
    • , Keiko HommaAffiliated withCentral clinical Laboratories, Keio University Hospital
    • , Tomonobu HasegawaAffiliated withDepartment of Pediatrics, Keio University School of Medicine
    • , Toyojiro MatsuishiAffiliated withDepartment of Pediatrics and Child Health, Kurume University School of Medicine

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Abstract

Background and aims

In two Japanese infants with neonatal cholestasis, 3-oxo-Δ4-steroid 5β-reductase deficiency was diagnosed based on mutations of the SRD5B1 gene. Unusual bile acids such as elevated 3-oxo-Δ4 bile acids were detected in their serum and urine by gas chromatography–mass spectrometry. We studied effects of oral chenodeoxycholic acid treatment.

Patients and methods

SRD5B1 gene analysis used peripheral lymphocyte genomic DNA. Diagnosis and treatment of these two patients were investigated retrospectively and prospectively investigated.

Results

With respect to SRD5B1, one patient was heterozygous (R266Q, a novel mutation) while the other was a compound heterozygote (G223E/R261C). Chenodeoxycholic acid treatment was effective in improving liver function and decreasing unusual bile acids such as 7α-hydroxy- and 7α,12α-dihydroxy-3-oxo-4-cholen-24-oic acids in serum and urine.

Conclusion

Primary bile acid treatment using chenodeoxycholic acid was effective for these patients treated in early infancy before the late stage of chronic cholestatic liver dysfunction.