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,Daniela Marchetti,Maria Iascone,Giuseppe Maggiore,Giuseppe Giordano,Gaetana Anna Rispoli,Mauro Naturale

doi:10.4081/pr.2017.7266

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.

Highlights

Grazia Bossi,[1] Giuseppe Giordano,[2] Gaetana Anna Rispoli,[3] Giuseppe Maggiore,[4] Mauro Naturale,[2] account for about 2% of liver disorders, and currently nine anomalies in bile acids (BAs) biosynthetic pathway have been definitely character
Serum liver enzymes can be normal in the early stages of the disease, but later show progressive increases; despite hypervarying degrees of giant cell transformation, probably secondary to the toxic injury.[17]
The combination of a cholestatic condition with normal GGT and without pruritus should alert physicians to investigate the possibility of the CBAS1 disorder.[14,15]

Summary

Introduction

Grazia Bossi,[1] Giuseppe Giordano,[2] Gaetana Anna Rispoli,[3] Giuseppe Maggiore,[4] Mauro Naturale,[2] account for about 2% of liver disorders, and currently nine anomalies in BAs biosynthetic pathway have been definitely character-. Cholestatic jaundice, but the clinical features and the symptom progression are quite heterogeneous, some carriers of this disorder being asymptomatic.[12,14] Additional clinical features may include hepatomegaly with or without splenomegaly, steatorrhoea with fat-soluble vitamin malabsorption and failure to thrive; pruritus is absent in most instances.[15] The CBAS1 disorder should be considered in cases of rickets unrelated to malnutrition and without overt liver disease.[16] Serum liver enzymes can be normal in the early stages of the disease, but later show progressive increases; despite hypervarying degrees of giant cell transformation, probably secondary to the toxic injury.[17] In the absence of specific treatment, the disease progresses to end-stage liver failure with cirrhosis, requiring liver transplantation.

Results

Conclusion