CAJ | 학술논문

目的了解甲基丙二酸血症(MMA)肾脏损害患儿的临床特点、遗传学背景、治疗效果、转归和预后,提高本病的诊断和治疗水平.方法收集2007年1月至2013年12月首都医科大学附属北京儿童医院收治的MMA患儿的病例资料,总结、分析合并肾脏损害患儿的临床表现、实验室、影像学、肾脏组织病理学检查结果、基因分析、治疗情况,并随访3个月～7年.结果 296例MMA患儿中,28例(9.5％)合并肾脏损害,男19例,女9例;18例合并高同型半胱氨酸血症.确诊年龄为2d～13岁,16例首发症状为蛋白尿、血尿、水肿,9例合并急性肾衰竭,5例继发溶血尿毒综合征,6例病初诊断为肾病综合征,予足量糖皮质激素治疗未见好转.患儿尿常规均出现蛋白尿(241～3060mg/d),甲基丙二酸水平与尿蛋白量呈正相关(r=0.982,P=0.003),尿β2-微球蛋白[(360.386±231.496) μg/L]、视黄醇结合蛋白[(338.537±243.293) μg/L]升高.肾外系统表现为精神、智力及体格发育落后、抽搐、贫血等.2例患儿有阳性家族史.肾组织病理提示系膜细胞及系膜基质增生增宽,系膜区未见明确的电子致密物沉积,肾小管上皮细胞肿胀变性,免疫荧光均阴性.3例行基因分析,分别为MMACHC的纯合突变(exon1:c.80A＞G,p.Q27R)及杂合突变(exon1:c.365A＞T,p.H122L;c.609 G＞A,p.W203X).患儿确诊后均予维生素B12等治疗.4例死亡,余经治疗尿甲基丙二酸水平明显下降,神经系统症状改善,精神状态和肾功能好转.结论 MMA可合并肾脏损害,多合并较严重的肾小管、肾小球功能受损,早期诊断很关键,及时治疗可有效控制病情,改善预后.
목적 료해갑기병이산혈증(MMA)신장손해환인적림상특점、유전학배경、치료효과、전귀화예후,제고본병적진단화치료수평.방법 수집2007년1월지2013년12월수도의과대학부속북경인동의원수치적MMA환인적병례자료,총결、분석합병신장손해환인적림상표현、실험실、영상학、신장조직병이학검사결과、기인분석、치료정황,병수방3개월～7년.결과 296례MMA환인중,28례(9.5％)합병신장손해,남19례,녀9례;18례합병고동형반광안산혈증.학진년령위2d～13세,16례수발증상위단백뇨、혈뇨、수종,9례합병급성신쇠갈,5례계발용혈뇨독종합정,6례병초진단위신병종합정,여족량당피질격소치료미견호전.환인뇨상규균출현단백뇨(241～3060mg/d),갑기병이산수평여뇨단백량정정상관(r=0.982,P=0.003),뇨β2-미구단백[(360.386±231.496) μg/L]、시황순결합단백[(338.537±243.293) μg/L]승고.신외계통표현위정신、지력급체격발육락후、추휵、빈혈등.2례환인유양성가족사.신조직병리제시계막세포급계막기질증생증관,계막구미견명학적전자치밀물침적,신소관상피세포종창변성,면역형광균음성.3례행기인분석,분별위MMACHC적순합돌변(exon1:c.80A＞G,p.Q27R)급잡합돌변(exon1:c.365A＞T,p.H122L;c.609 G＞A,p.W203X).환인학진후균여유생소B12등치료.4례사망,여경치료뇨갑기병이산수평명현하강,신경계통증상개선,정신상태화신공능호전.결론 MMA가합병신장손해,다합병교엄중적신소관、신소구공능수손,조기진단흔관건,급시치료가유효공제병정,개선예후.
Objective To understand the clinical characteristics, treatment effect and prognosis of children with methylmalonic acidemia (MMA) combined with renal damage, and to provide experiences about how to improve the level of diagnosis and treatment.Methods The medical records of children with MMA were collected from January of 2007 to December of 2013 in Beijing Children's Hospital Affiliated to Capital University of Medical Sciences,while the clinical manifestations,laboratory findings, imaging material, inspection results were analyzed, and the renal pathological gene analysis, treatment effect, and prognosis of MMA children with renal damage were studied, and follow-up was carried out for 3 months up to 7 years.Results Among the two hundred and ninety-six cases of MMA,28 cases (9.5％) with renal damage,including 19 boys and 9 girls, 18 patients with hyperhomocysteinemia.Their ages varied from 2 days to 13 years old when confirmed.The first symptoms of 16 cases were proteinuria, hematuria, and edema, 9 cases were complicated with acute renal failure,5 cases were diagnosed as hemolytic uremic syndrome,6 patients were diagnosed as nephrotic syndrome, receiving enough glucocorticoids treatment without improvement.The routine examination of the urine showed that proteinuria (241-3 060 mg/d), methylmalonic acid levels and urinary protein were positively correlated (r =0.982, P =0.003), as urinary β2-microglobulin [(360.386 ± 231.496) μg/L], retinol binding protein [(338.537 ± 243.293) μg/L] increased.Extrarenal clinical manifestations were the spiritual, mental and physical development retardations, seizures, anemia etc.Two cases had a positive family history.Renal pathology showed mesangial cells and mesangial matrix proliferation broadening, no electron dense deposits in mesangial area, renal tubular epithelial cell swelling degeneration, and immunofluorescence was negative.Gene analysis of 3 cases showed exon1:c.80A ＞ G,p.Q27R and exon1 :c.365A ＞ T,p.H122L/c.609 G ＞ A,p.W203X.Children with MMA were treated with vitamin B12 treatment.Two cases of multiple organ failure died during hospitalization, and 2 cases died after leaving hospital.After treatment, the level of urinary methylmalonic acid was significantly decreased, while nervous system symptoms improved significantly, and the mental state and the renal function were improved.Conclusions MMA may be associated with kidney damage,usually with severe renal tubular and glomerular impairment.Early diagnosis is the key,and timely treatment can effectively control the disease, improve the prognosis.