Study On The Clinical And Genetic Characteristics Of Rickets Related To Hereditary Renal Tubular Disease

Objective:To analyze the clinical and genetic characteristics of hypophosphatemia rickets which aim to improve the cognition of clinicians with this disease and provide reference for diagnosis and treatment..Methods:Patients visited in Hunan Children's Hospital due to rickets and hypophosphatemic from January 2015 to December 2019 who performed the whole exome sequencing.Their clinical data and the results of genetic testing were summarized and analyzed.Results:?1?In twenty cases,twelve were male?60%?,eight were female?40%?,the ratio of gender is 1.5:1,the median age was 3.79?2.94,6.49?years old,eighteen cases?90%?with stage of disease more than one year,the median age of onset was 1 year old,and ten cases had family medical history.?2?All of them had slow growing development.Biochemical investigations showed hypophosphatemia,four cases?20%?with hypokalemia and two cases?10%?with hypocalcemia.Alkaline phosphatase was significantly increased in 10 cases?50%?were 604.62?549.50,972.00?U/L,10 cases?50%?were at the normal range.There were five cases?25%?with 25 hydroxyvitamin D deficiency which were 48.33?26.99,48.94?ng/mL and fifteen cases?75%?in normal level.The parathyroid hormone increased in eight cases?40%?were 80.80?73.03,218.43?ng/L,and normal in twelve cases?60%?.?3?Eighteen cases detected significative gene variation included eleven cases?61.1%?of PHEX gene variation which diagnosed as HR,and one of them with OCRL gene variation at the same time,four cases?22.2%?of SLC4A1 gene variation were diagnosed as RTA,two cases?11.1%?respectively CYP27B1 and VDR gene variation which diagnosed as VDDR,one case?5.6%?of CLCN5 gene variation diagnosed as Dent disease.Six variation sites have not been reported included PHEX gene?c.1328 G > A;c.1665₁673delinsG?,SLC4A1 gene?c.694+1G>A?,VDR gene?c.906-4G>C,c.160A>G?and CYP27B1 gene?c.823delG?.Conclusion:HR is the most common reason of rickets related to hereditary renal tubular disease which clinical manifestations are short stature and genu varum deformity and more common in male patients who appear more serious hypophosphatemia with the disorder of secretion about parathroid hormone.HR is a rare hereditary disease which the most common variation gene is PHEX with nonsense variation of 16 Exon.