Lei Yin1,2, Youying Mao3, Yunfang Zhou4, Yongnian Shen4, Huijin Chen4, Wei Zhou3, Yanliang Jin5, Hua Huang5, Yongguo Yu6, Jian Wang7. 1. Department of Nephrology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, People's Republic of China. yinlei@scmc.com.cn. 2. Special Consultation Clinic for Rare and Complicated Diseases, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. yinlei@scmc.com.cn. 3. Department of Nephrology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, People's Republic of China. 4. Special Consultation Clinic for Rare and Complicated Diseases, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. 5. Department of Rheumatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. 6. Department of Pediatric Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. 7. Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, People's Republic of China. Labwangjian@shsmu.edu.cn.
Abstract
OBJECTIVES: Most patients with progressive pseudorheumatoid dysplasia (PPRD) are initially misdiagnosed because of disease rarity and lack of awareness by most clinicians. The purpose of this study was to provide further early diagnostic options and potential treatment to patients with PPRD. METHODS: A retrospective study was performed by collecting and organizing clinical manifestations, radiographic features, laboratory test results, genetic test outcome, treatment, and follow-up records of the patients with PPRD. Age of diagnosis and genotype-phenotype correlation were further analyzed. RESULTS: Nine PPRD children with causative CCN6 mutation were included. There were 3 pairs of siblings and 1 patient from inbred family. Five patients were primarily misdiagnosed as juvenile idiopathic arthritis (JIA). The interval between onset of symptoms and definite diagnosis of 8 patients varied from 3.6 to 20 years. Symptoms at the onset included enlarged and stiff interphalangeal joints of the fingers, gait disturbance, or joint pain. Laboratory tests revealed normal range of inflammatory parameters. Radiographic findings disclosed different degrees of abnormal vertebral bodies and epiphyseal enlargement of the interphalangeal joints. After the treatment of calcitriol in 5 patients with low level 25-hydroxyvitamin D3 for around 1.25 years to 1.75 years, 2 patients kept stable, while 3 of them improved gradually. CONCLUSIONS: Combining the patient's family history, clinical features, normal inflammatory markers, and the characteristic radiographic findings, the clinical diagnosis of PPRD for the patients could be obtained at very early stage of the disease. The patients with PPRD carrying c.624dupA variant in CCN6 may have delayed onset. Underlying vitamin D deficiency should be sought and corrected in patients with PPRD.
OBJECTIVES: Most patients with progressive pseudorheumatoid dysplasia (PPRD) are initially misdiagnosed because of disease rarity and lack of awareness by most clinicians. The purpose of this study was to provide further early diagnostic options and potential treatment to patients with PPRD. METHODS: A retrospective study was performed by collecting and organizing clinical manifestations, radiographic features, laboratory test results, genetic test outcome, treatment, and follow-up records of the patients with PPRD. Age of diagnosis and genotype-phenotype correlation were further analyzed. RESULTS: Nine PPRD children with causative CCN6 mutation were included. There were 3 pairs of siblings and 1 patient from inbred family. Five patients were primarily misdiagnosed as juvenile idiopathic arthritis (JIA). The interval between onset of symptoms and definite diagnosis of 8 patients varied from 3.6 to 20 years. Symptoms at the onset included enlarged and stiff interphalangeal joints of the fingers, gait disturbance, or joint pain. Laboratory tests revealed normal range of inflammatory parameters. Radiographic findings disclosed different degrees of abnormal vertebral bodies and epiphyseal enlargement of the interphalangeal joints. After the treatment of calcitriol in 5 patients with low level 25-hydroxyvitamin D3 for around 1.25 years to 1.75 years, 2 patients kept stable, while 3 of them improved gradually. CONCLUSIONS: Combining the patient's family history, clinical features, normal inflammatory markers, and the characteristic radiographic findings, the clinical diagnosis of PPRD for the patients could be obtained at very early stage of the disease. The patients with PPRD carrying c.624dupA variant in CCN6 may have delayed onset. Underlying vitamin D deficiency should be sought and corrected in patients with PPRD.
Authors: Sofia Torreggiani; Marta Torcoletti; Belinda Campos-Xavier; Francesco Baldo; Carlo Agostoni; Andrea Superti-Furga; Giovanni Filocamo Journal: Rheumatol Int Date: 2018-10-16 Impact factor: 2.631