Atypical clinical presentation and successful treatment with oral cholic acid of a child with defective bile acid synthesis due to a novel mutation in the HSD3B7 gene

Grazia Bossi; Giuseppe Giordano; Gaetana Anna Rispoli; Giuseppe Maggiore; Mauro Naturale; Daniela Marchetti; Maria Iascone

doi:10.4081/pr.2017.7266

Atypical clinical presentation and successful treatment with oral cholic acid of a child with defective bile acid synthesis due to a novel mutation in the HSD3B7 gene

Pediatr Rep. 2017 Oct 10;9(3):7266. doi: 10.4081/pr.2017.7266. eCollection 2017 Oct 6.

Authors

Grazia Bossi¹, Giuseppe Giordano², Gaetana Anna Rispoli³, Giuseppe Maggiore⁴, Mauro Naturale², Daniela Marchetti⁵, Maria Iascone⁵

Affiliations

¹ Pediatric Department, IRCCS Foundation Policlinico San Matteo, Pavia.
² Mass Spectrometry Laboratory, Women's and Children's Health Department, University of Padua, Institute for Pediatric Research (IRP), Padua.
³ Department of Radiology, US Pediatric Radiology, IRCCS Foundation Policlinico San Matteo, Pavia.
⁴ Department of Medical Science, Pediatric Section, University of Ferrara.
⁵ Laboratory of Genetic Medicine, ASST Papa Giovanni XXIII, Bergamo, Italy.

Abstract

We report definitive diagnosis and effective treatment with oral cholic acid in one Italian male child affected by 3β-hydroxy-Δ⁵-C²⁷-steroid dehydrogenase (3β-HSD) deficiency. He presented with failure to thrive, hepatomegaly and multiple cystic images in kidneys; no biochemical evidence of cholestasis. Large amounts of bile acid metabolites was detected in urine by fast atom bombardment ionization mass spectrometry (FAB-MS). HSDH3B7 gene analysis identified one mutation in intron 4, at nucleotide 432, G>A substitution that has never been reported before.The replacement therapy with oral cholic acid started early after the diagnosis and is still ongoing. Three years later hepatomegaly is no longer evident, liver function is normal and the child is growing regularly. In our experience, clinical features of 3β-HSD deficiency can be very poor and even cholestasis can lack at diagnosis. Early replacement therapy with cholic acid is safe and leads to clinical and biochemical control of the disease.

Keywords: cholic acid; genetic cholestasis.

Grants and funding

Funding: the final stage of manuscript preparation before submission was supported by an unrestricted grant from Laboratories CTRS (63, rue de l’Est; 92100 Boulogne Billancourt; France). The sponsor had no involvement in study design; the collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the manuscript for publication.