Absence of Mutation in Coding Regions of CYP2R1 Gene in Apparent Autosomal Dominant Vitamin D 25-Hydroxylase Deficiency Rickets

Abstract

CONTEXT: This is a case report of a proband and his family presenting with apparent autosomal dominant 25-hydroxylase enzyme deficiency and bone disease. OBJECTIVE: The aim of the study was to present an alternative pattern of transmission of 25-hydroxylase enzyme deficiency other than autosomal recessive. DESIGN: We diagnosed our patient with 25-hydroxylase enzyme deficiency, treated him, and examined his DNA for mutations. Evaluations at other institutions, clinical history of all family members, and laboratory testing for the mother, aunt, and maternal grandmother were reviewed. Family consent was obtained for all testing and record review. SETTING: The patient was evaluated serially in an outpatient clinic. Routine laboratory studies for proband, mother, and maternal grandmother were obtained. Genetic testing was performed in another institution after obtaining family consent. INTERVENTIONS: No research intervention was performed. MAIN OUTCOME MEASURES: Routine clinical care included an evaluation of growth pattern. Laboratory evaluation included 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], alkaline phosphatase, intact PTH, phosphate, calcium, ionized calcium, and magnesium levels. RESULTS: Results showed consistently low 25-hydroxylase enzyme function. They also showed elevated alkaline phosphatase and PTH, as well as decreased phosphate and calcium. These abnormalities were corrected with 1,25(OH)(2)D therapy. CONCLUSION: We conclude that 25-hydroxylase enzyme deficiency can be inherited in an autosomal dominant pattern. This case raises a question about different tributary pathways affecting the function of the 25-hydroxylase enzyme. Physiological dosing of 1,25(OH)(2)D was sufficient for treatment. There were no detectable mutations in any of the coding regions of the gene or its intronic junctions.