Background: Vitamin D dependent rickets type 1A (VDDR1A) is a rare disease caused by CYP27B1 mutations which encodes vitamin D 1α-hydoxylase.
Objective and hypotheses: Vitamin D dependent rickets type 1A features of three Chinese cases with CYP27B1 mutations and report the experience of medication for severe hypocalcaemia.
Method: Summarise their clinical features analyse the CYP27B1 and vitamin D receptor (VDDR) mutations.
Results: There were one 1.2 years boy and two girls of 2 and 2.7 years old on their admissions. All of them had typical signs of rickets. Two had pathological fractures and predominant lower limbs deformities while one girl only presented with delayed walking until she was 2 years old. They had hypocalcaemia (1.171.59 mmol/l), high alkaline phosphatase level (904.62240 U/l) accompanied with elevated PTH level (492.31238.4 pg/ml). Serum 25-(OH) D3 levels were normal to high 27105.2 ng/ml and 1.25(OH)2D3 levels were low(3.2110.02 pg/ml). In genetic analysis, they were all shown to have compound heterozygous mutations of CYP27B1 gene (see table 1). All patients were treated with calcium and calcitriol. Two of the female patient can stand up steadily 3 months after treatment and walk steadily 6 months later. A female patient suffered from bone hungry syndrome was taken calcium intravenous infusion continuously for 3 days. The male patients died of severe pneumonia 1 month after discharged.
|1||485T>A/1086T>A||Missense/synonymous||162 V>D/362 T>T|
|3||1325 CCCACCC,ins/1442 A del||Truncated/frame shift||Truncated/protein changed|
Conclusion: Patients with VDDR 1A have a wide spectrum of clinical manifestations varying from mild to severe, even pathogenic fractures. They can be cured by high dose calcitriol and calcium supplementation. Intravenous injection may be needed because of severe bone hungry. The mutation of c.1325 CCCACCC might be a hot spot of CYP27B1 in VDRR1A, which has been reported in several of families.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology