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Case Reports
. 2025 Jan 14;38(5):546-550.
doi: 10.1515/jpem-2024-0454. Print 2025 May 26.

Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes

Merve Yoldaş Çelik  1 , Burcu Köşeci  1 , Ezgi Burgaç  1 , Sevinç Garip  2 , Fatma Ilknur Varol  3 , Şükrü Güngör  3 , Didem Gulcu Taskin  2 , Kanay Yararbaş  4   5
Affiliations
Case Reports

Expanding the genotypic spectrum of 3β-hydroxy-δ5-C27-steroid dehydrogenase (HSD3B7) deficiency: novel mutations and clinical outcomes

Merve Yoldaş Çelik et al. J Pediatr Endocrinol Metab. .

Abstract

Objectives: HSD3B7 deficiency is a genetic disorder caused by mutations in the HSD3B7 gene, leading to impaired bile acid synthesis and the accumulation of toxic intermediates. Affected patients typically present with cholestatic liver disease, including jaundice and progressive liver dysfunction.

Case presentation: This case series describes three pediatric patients from two families diagnosed with HSD3B7 deficiency, each demonstrating varying clinical severity and outcomes. All cases exhibited cholestasis with normal GGT levels and elevated AST/ALT. Case 1, a male infant, also presented with craniosynostosis and failure to thrive, responding well to cholic acid therapy. Case 2, a female infant and first cousin of Case 1, had mild cardiac abnormalities and showed slight improvement with ursodeoxycholic acid and vitamin supplementation. Case 3, a male infant with a compound HSD3B7 and ATP8B1 mutation, progressed to fulminant liver failure, ultimately requiring a liver transplant. A novel c.531 + 1G>C variant was identified in Cases 1 and 2, contributing to understanding genotype-phenotype correlations in bile acid synthesis disorders.

Conclusions: Early diagnosis and treatment with bile acid therapy are crucial for improving outcomes, although some cases may necessitate liver transplantation. This series emphasizes the need to consider bile acid synthesis disorders in the differential diagnosis of cholestasis.

Keywords: 3β-hydroxy-δ5-C27-steroid dehydrogenase deficiency; HSD3B7; bile acid; cholestasis; cholic acid.

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References

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