CYP3A4 Mutation Causes Vitamin D-Dependent Rickets Type 3: A Case Report in Saudi Arabia

Rickets is a childhood disorder of vitamin D deficiency that is characterized by growth retardation and impairment in skeletal mineralization. Vitamin D deficiency is usually due to decreased dietary vitamin D intake, decreased sunlight exposure, or genetic defects. A recurrent gain-of-function missense mutation (p.I301T) in the gene encoding CYP3A4 has been identified as a cause of excessive inactivation of vitamin D metabolites that causes vitamin D-dependent rickets type 3 (VDDR3). We hereby report a case of a six-year-old girl with poor growth and bone deformities, such as genu valgum. In addition, the patient has a strong family history of short stature and bone deformities. She continues to receive multidisciplinary care, and the finding of a heterozygous missense variant in CYP3A4: c.902 T > C; p.Ile301Thr in the CYP3A4 gene confirms the diagnosis of VDDR3. To our knowledge, this is the first case to be reported in Saudi Arabia and the fourth case in the literature. Our findings highlight the importance of vitamin D in those with high activity in CYP3A4 to maintain vitamin D hemostasis, and we need to reach optimal doses to help them maintain their biochemical and radiological finding within the normal range.