Vitamin D-deficiency rickets, not responding to large treatment doses of oral Vitamin D, suggest rare receptor mutations, malabsorption, or hepatobiliary dysfunction. We present a set of twins of Hispanic origin who presented with refractory Vitamin D-deficiency rickets and failure to thrive (FTT) at 6 months of age. On follow-up, mild elevations in serum alanine transaminases and normal aspartate aminotransferase were noted. Subsequently, patients manifested fat-soluble vitamin deficiencies. More targeted evaluations revealed a diagnosis of 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. Treatment with oral bile acid replacement with cholic acid resolved rickets and promoted weight gain. Bile acid synthesis disorders should be suspected in refractory rickets in infancy, particularly in a clinical setting of FTT, even in the absence of substantial abnormalities in liver-function tests.