Journal of Inherited Metabolic Disease

, Volume 36, Issue 3, pp 565–573 | Cite as

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

  • Yoshitaka Seki
  • Tatsuki Mizuochi
  • Akihiko Kimura
  • Tomoyuki Takahashi
  • Akira Ohtake
  • Shin-Ichi Hayashi
  • Toshiya Morimura
  • Yasuharu Ohno
  • Takayuki Hoshina
  • Kenji Ihara
  • Hajime Takei
  • Hiroshi Nittono
  • Takao Kurosawa
  • Keiko Homma
  • Tomonobu Hasegawa
  • Toyojiro Matsuishi
Original Article

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.

Abbreviations

5β-reductase

3-oxo-Δ4-steroid 5β-reductase

TBA

total bile acids

GGT

γ-glutamyltransferase

3β-HSD

3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase

ALT

alanine aminotransferase

GC-MS

gas chromatography–mass spectrometry

CDCA

chenodeoxycholic acid

AST

aspartate aminotransferase

UDCA

ursodeoxycholic acid

Cr

creatinine

CMV

cytomegalovirus

CA

cholic acid

Notes

Conflict of interest

None.

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Copyright information

© SSIEM and Springer 2012

Authors and Affiliations

  • Yoshitaka Seki
    • 1
  • Tatsuki Mizuochi
    • 1
  • Akihiko Kimura
    • 1
  • Tomoyuki Takahashi
    • 1
    • 2
  • Akira Ohtake
    • 3
  • Shin-Ichi Hayashi
    • 4
  • Toshiya Morimura
    • 4
  • Yasuharu Ohno
    • 4
  • Takayuki Hoshina
    • 5
  • Kenji Ihara
    • 5
  • Hajime Takei
    • 6
  • Hiroshi Nittono
    • 6
  • Takao Kurosawa
    • 7
  • Keiko Homma
    • 8
  • Tomonobu Hasegawa
    • 9
  • Toyojiro Matsuishi
    • 1
  1. 1.Department of Pediatrics and Child HealthKurume University School of MedicineKurume-shiJapan
  2. 2.Division of Gene Therapy and Regenerative Medicine, Cognitive and Molecular Research Institute of Brain DiseaseKurume UniversityKurumeJapan
  3. 3.Department of Pediatrics, Faculty of MedicineSaitama Medical UniversitySaitamaJapan
  4. 4.Department of Pediatric Surgery, Faculty of MedicineSaitama Medical UniversitySaitamaJapan
  5. 5.Department of Pediatrics, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  6. 6.Institution of Bile Acid, Junshin ClinicTokyoJapan
  7. 7.Faculty of Pharmaceutical SciencesHealth Sciences University of HokkaidoHokkaidoJapan
  8. 8.Central clinical LaboratoriesKeio University HospitalTokyoJapan
  9. 9.Department of PediatricsKeio University School of MedicineTokyoJapan

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