[Infant with 3β-hydroxy-Δ(5)-C27 steroid dehydrogenase deficiency: report of two cases and literatures review].

OBJECTIVE: To study the clinical characteristics and early diagnosis of children with 3β-hydroxy-Δ(5)-C27-steroid dehydrogenase (3β-HSD) deficiency.

METHOD: Data related to clinical characteristics, serum biochemistry, liver pathology, gene mutations and treatment of two children with 3β-HSD deficiency were analyzed and relevant literature was reviewed. Fifty-three cases of 3β-HSD deficiency were reported since 1993 in the world.

RESULT: (1) Both patients showed neonatal cholestasis, blood biochemical examination of patient one showed alanine aminotransferase 292 U/L, aspartate aminotransferase 458 U/L, serum bile acids 1.8 µmol/L, total bilirubin 125.6 µmol/L, direct bilirubin 93.8 µmol/L, γ-glutamyl endopeptidase 43 U/L, bile biochemical test revealed bile acid 17.4 µmol/L, no itching; another patient showed alanine aminotransferase 812 U/L, aspartate aminotransferase 819 U/L, serum bile acids 4.9 µmol/L, total bilirubin 151.3 µmol/L, direct bilirubin 108.8 µmol/L, γ-glutamyl endopeptidase 50 U/L, bile biochemical test revealed bile acid 66.0 µmol/L, there was no itching. Both patients were confirmed by HSD3B7 gene mutation analysis. One patient had a homozygous mutation: 130_131insA, a novel mutation had not been reported, the other had compound heterozygous mutations: 544insG and 790C>C/A; The electron microscopic findings included bile pigment granules, fat droplets deposited in the cytoplasm of hepatocytes, glycogen granules increased, bile ductular dilatation or proliferation, bile plugs in canaliculus, biliary epithelial microvilli reduced, chronic inflammatory cell infiltration; (2) 53 cases were diagnosed by urine gas chromatography mass spectrometry (GC/MS) or fast atom bombardment mass spectrometry (FAB-MS), while 33 cases were diagnosed by HSD3B7 gene mutation analysis. All the patients had cholestatic jaundice, 22 cases of hepatomegaly, fats and fat-soluble vitamin malabsorption in 14 cases, blood γ-GT normal or decreased in 53 cases, normal or decreased serum bile acid in 53 cases, 49 cases had no skin itching. Two children were not treated before the age of 5, 1 child before the age of 13 were not treated in time, progressed to cirrhosis.

CONCLUSION: 3β-hydroxy-Δ(5)-C27-steroid dehydrogenase is the most common bile acid synthetic defects described to date. The clinical presentation of this disorder include neonatal cholestasis, low or normal serum total bile acid concentration and a normal serum γ-GT concentration, bile acid significantly reduced in the bile. Definitive diagnosis can be achieved by gene analysis; Prompt diagnosis and early treatment are essential, primary bile acid treatment leads to clinical and biochemical control and prevents chronic liver disease.