Distinguishing primary from secondary Δ4-3-oxosteroid 5β-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis

Summary Objective Deficiency of Δ4‐3‐oxosteroid 5β‐reductase (5β‐reductase), a bile acid synthesis disorder, presents findings of neonatal cholestasis and hyper‐3‐oxo‐Δ4 bile aciduria. The 5β‐reductase enzyme participates in not only bile acid synthesis but also hepatic steroid metabolism. Deficiency of 5β‐reductase includes 2 types: primary deficiency, with an SRD5B1 gene mutation; and secondary deficiency, lacking a mutation. Secondary deficiency is caused by fulminant liver failure from various aetiologies including neonatal hemochromatosis (NH). Distinguishing primary from secondary deficiency based on γ‐glutamyltransferase (GGT), serum total bile acids (TBA), and urinary bile acid analysis using gas chromatography–mass spectroscopy (GC‐MS) is very difficult. SRD5B1 gene analysis is the only reliable method. We examined urinary steroid analysis as a way to distinguish primary from secondary 5β‐reductase deficiency. Design, patients and measurements We examined 12 patients with cholestatic jaundice, normal or slightly elevated GGT, and hyper‐3‐oxo‐Δ4 bile aciduria using urinary steroid analysis by GC‐MS of both cortisol and cortisone compounds, such as 5β‐tetrahydrocortisol (5β‐THF) and 5β‐tetrahydrocortisone (5β‐THE). Patients previously were diagnosed with primary 5β‐reductase deficiency (n = 3), deficiency secondary to NH (n = 3) and deficiency secondary to other liver disorders (n = 6). Results Urinary steroid analysis in 3 primary deficiency and 3 NH patients showed low 5β‐THE and elevated 5α/5β‐THE ratios, making distinction difficult without also considering the clinical course and abdominal magnetic resonance imaging (MRI) findings, such as a very low signal intensity in liver and/or pancreas, especially in T2‐weighted images. In the six patients with other secondary deficiencies, urinary 5β‐THF and 5α/5β‐THF differed from those in primary deficiency (P