阿德福韦酯致范科尼综合征合并骨软化

Fanconi syndrome and osteomalacia induced by adefovir dipivoxil

1例46岁男性慢性乙型肝炎患者10年前开始规律服用阿德福韦酯(10 mg,1次/d),近3年出现进行性加重的胸背部疼痛,近1年出现四肢乏力、行走困难。体格检查:颈椎、上胸椎水平椎体和肩胛骨、肋骨处压痛,肋弓外翻,直腿抬高试验阳性。实验室检查:血钾3.1 mmol/L,氯111 mmol/L,钙2.2 mmol/L,磷0.53 mmol/L,尿酸117μmol/L,空腹葡萄糖4.1 mmol/L,碱性磷酸酶(ALP)201 U/L,乙型肝炎表面抗原、e抗体、核心抗体均为阳性;尿葡萄糖(++),蛋白质(+),微量白蛋白70.9 mg/L,α1微球蛋白168.0 mg/L,蛋白定量0.93g/24 h。肾动态显像检查显示双肾肾小球滤过功能中度受损。血气分析示pH 7.24,二氧化碳分压31 mmHg(1 mmHg=0.133 kPa),碳酸氢根浓度13 mmol/L。全身骨扫描提示全身多发骨代谢活跃灶;X线胸片示两胸部多发性肋骨骨折;骨密度测定示重度骨质疏松。诊断为阿德福韦酯致范科尼综合征合并骨软化。停用阿德福韦酯,予补钙和补磷等治疗。6 d后复查,血磷升至0.71 mmol/L。出院后继续服用上述药物治疗。半年后复查,患者可大步行走,血磷0.81 mmol/L。

A 46-year-old male patient with chronic hepatitis B received regularly adefovir dipivoxil 10 mg once daily for more than ten years. Progressive chest pain occured in the recent 3 years and limb weakness and difficult walking occurcd in recent one year. Physical examination showed that cervical vertebra and upper thoracic vertebra, scapula and rib had tenderness, rib bows were everted, and straight- leg-raising test was positive. Laboratory examination showed the following results： serum potassium 3.1 mmoL/L, chloride 111 mmol/L, calcium 2.2 retool/L, phosphorus 0.53 mmol/L, uric acid ll7 mmol/L, fasting plasma glucose 4.1 mmol/L, alkaline phosphatase 201 U/L; positive hepatitis B surface antigen, e antibody, and core antibody; urine glucose （ ＋＋ ） , protein （ ＋ ） , microalbumin 70.9 mg/L, al-micro- globulin 168.0 mg/L, and urine quantitative protein 0.93 g/24 h. Renal dynamic imaging examination showed that the glomerular filtration function was moderately impaired in bilateral kidney. Blood gas analysis showed pH 7.24, partial pressure of carbon dioxide 31 mmHg, and bicarbonate concentration 13 mmol/L. Whole-body bone scan showed multiple bone metabolism active lesions. X-ray screening showed multiple fractures of ribs. Bone mineral density measurement showed severe osteoporosis. Fanconi syndrome and osteomalacia induced by adefovir dipivoxil were diagnosed. Adefovir dipivoxil was replaced with entecavir. Treatments with calcium and phosphate supplement were given. Six days after the above treatments, serum phosphorus level rose to 0.71 mmol/L. The above treatments were continued after the patient was discharged. Haft a year later, he could walk with long strides and his serum phosphorus level was 0.81 mmol/L.