Clinical Characteristics and Bone Features of Autosomal Recessive Hypophosphatemic Rickets Type 1 in Three Chinese Famil
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ORIGINAL RESEARCH
Clinical Characteristics and Bone Features of Autosomal Recessive Hypophosphatemic Rickets Type 1 in Three Chinese Families: Report of Five Chinese Cases and Review of the Literature Xiaolin Ni1 · Xiang Li1 · Qi Zhang2 · Chang Liu1 · Yiyi Gong3 · Ou Wang1 · Mei Li1 · Xiaoping Xing1 · Yan Jiang1 · Weibo Xia1 Received: 14 June 2020 / Accepted: 2 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Autosomal recessive hypophosphatemic rickets type 1 (ARHR1) was reported to be caused by homozygous mutation of dentin matrix protein 1 (DMP1). To date, very few cases have been reported. Here, we summarized clinical, laboratory and imaging findings of ARHR1 patients in our hospital. Literature review was performed to analyze genotype–phenotype correlation. Five Chinese patients from three unrelated pedigrees presented with lower extremity deformity and short stature. Hypophosphatemia, elevated alkaline phosphatase, high intact fibroblast growth factor 23 and sclerostin were found. X-ray uncovered coexistence of osteomalacia and osteosclerosis. Although areal bone mineral density (aBMD) of axial bone measured by dual-energy X-ray absorptiometry was relatively high in all patients, volumetric BMD (vBMD) and microstructure of one adult patient’s peripheral bone detected by HR-pQCT were damaged. Mutation analyses of DMP1 revealed three homozygous mutations including two novel mutations, c.54 + 1G > C and c.94C > A (p.E32X), and a reported mutation c.184-1G > A. Genotype–phenotype correlation analysis including 30 cases (25 from literature review and 5 from our study) revealed that patients harboring mutations affecting C-terminal fragment of DMP1 presented with shorter stature (Z score of height = − 3.4 ± 1.6 vs − 1.0 ± 1.6, p = 0.001) and lower serum phosphate level (0.70 ± 0.15 vs 0.84 ± 0.16, p = 0.03) than those harboring mutations only affecting N-terminal fragment. In summary, we reported five Chinese ARHR1 patients and identified two novel DMP1 mutations. High aBMD and local osteosclerosis in axial bone with low vBMD and damaged microstructure in peripheral bone were featured. Genotype–phenotype correlation analysis confirmed the important role of C-terminal fragment of DMP1. Keywords ARHR1 · DMP1 · iFGF23 · Osteosclerosis · HR-pQCT Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00223-020-00755-7) contains supplementary material, which is available to authorized users. * Yan Jiang [email protected] * Weibo Xia [email protected] 1
Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
2
Laboratory Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
3
Central Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
Introduction Hereditary hy
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