PDF(Pubmed)
Abstract：
UNASSIGNED: Pathogenic variants in TARS2 are associated with combined oxidative phosphorylation deficiency 21 (COXPD21), an autosomal recessive disorder usually presenting as mitochondrial encephalomyopathy. Kidney impairment has been documented in a minority of COXPD21 patients, mostly with distal renal tubular acidosis.
UNASSIGNED: We report on the first COXPD21 patient with generalized tubular dysfunction and early childhood progression to chronic kidney disease (CKD). Thorough diagnostic evaluation was initiated at six months of age due to failure to thrive, muscular hypotonia, motor delay and recurrent bronchiolitis. The boy was lost to follow-up until the age of two years, when he was readmitted with elevated creatinine level, reduced estimated glomerular filtrate rate, normochromic anaemia, metabolic acidosis and hyperkalaemia. Urine abnormalities pointed to generalized tubular dysfunction. Two novel heterozygous missense variants in TARS2 gene were detected by the means of whole exome sequencing: c.1298T>G (p.Phe438Cys) of maternal origin and c.1931A>T (p.Asp644Val) of paternal origin. Currently, at 4.5 years of age, the boy has failure to thrive, severe motor and verbal delay and end stage of CKD. We referred the patient to paediatric centre that provides renal replacement therapy.
UNASSIGNED: The overall clinical course in the patient we report on corresponds well to the previously reported cases of TARS2 related COXPD21, especially in regard to neurological and developmental aspects of the disease. However, we point out the generalized tubulopathy and early occurrence of CKD in our patient as atypical renal involvement in COXPD21. Additionally, this is the first report of hypothyroidism and hypoparathyroidism in a COXPD21 patient.
UNASSIGNED: We report on the first COXPD21 patient with generalized tubular dysfunction and early childhood progression to chronic kidney disease (CKD). Thorough diagnostic evaluation was initiated at six months of age due to failure to thrive, muscular hypotonia, motor delay and recurrent bronchiolitis. The boy was lost to follow-up until the age of two years, when he was readmitted with elevated creatinine level, reduced estimated glomerular filtrate rate, normochromic anaemia, metabolic acidosis and hyperkalaemia. Urine abnormalities pointed to generalized tubular dysfunction. Two novel heterozygous missense variants in TARS2 gene were detected by the means of whole exome sequencing: c.1298T>G (p.Phe438Cys) of maternal origin and c.1931A>T (p.Asp644Val) of paternal origin. Currently, at 4.5 years of age, the boy has failure to thrive, severe motor and verbal delay and end stage of CKD. We referred the patient to paediatric centre that provides renal replacement therapy.
UNASSIGNED: The overall clinical course in the patient we report on corresponds well to the previously reported cases of TARS2 related COXPD21, especially in regard to neurological and developmental aspects of the disease. However, we point out the generalized tubulopathy and early occurrence of CKD in our patient as atypical renal involvement in COXPD21. Additionally, this is the first report of hypothyroidism and hypoparathyroidism in a COXPD21 patient.
摘要：
■TARS2中的致病变体与联合氧化磷酸化缺陷21（COXPD21）有关，常染色体隐性遗传疾病，通常表现为线粒体脑肌病。在少数COXPD21患者中已记录到肾脏损害，多为远端肾小管酸中毒。
■我们报告了首例COXPD21患者的广泛性肾小管功能障碍和儿童早期进展为慢性肾脏病（CKD）。由于未能茁壮成长，在六个月大时开始了彻底的诊断评估，肌张力减退,运动延迟和复发性毛细支气管炎。这个男孩失去了随访，直到两岁，当他再次入院时肌酐水平升高，降低估计的肾小球滤过率，正常色素性贫血,代谢性酸中毒和高钾血症。尿液异常表明广泛性肾小管功能障碍。通过全外显子组测序检测到TARS2基因中的两个新的杂合错义变体：c.1298T>G（p。Phe438Cys）的母体来源和c.1931A>T（p。Asp644Val）父系起源。目前,在4.5岁时，这个男孩未能茁壮成长，严重的运动和言语延迟和CKD终末期。我们将患者转诊至提供肾脏替代治疗的儿科中心。
我们报告的患者的总体临床过程与先前报道的TARS2相关的COXPD21病例非常吻合，特别是在该疾病的神经和发育方面。然而,我们指出我们患者的广泛性肾小管病和CKD的早期发生是COXPD21的不典型肾脏受累。此外,这是COXPD21患者的甲状腺功能减退症和甲状旁腺功能减退症的首例报告.
■我们报告了首例COXPD21患者的广泛性肾小管功能障碍和儿童早期进展为慢性肾脏病（CKD）。由于未能茁壮成长，在六个月大时开始了彻底的诊断评估，肌张力减退,运动延迟和复发性毛细支气管炎。这个男孩失去了随访，直到两岁，当他再次入院时肌酐水平升高，降低估计的肾小球滤过率，正常色素性贫血,代谢性酸中毒和高钾血症。尿液异常表明广泛性肾小管功能障碍。通过全外显子组测序检测到TARS2基因中的两个新的杂合错义变体：c.1298T>G（p。Phe438Cys）的母体来源和c.1931A>T（p。Asp644Val）父系起源。目前,在4.5岁时，这个男孩未能茁壮成长，严重的运动和言语延迟和CKD终末期。我们将患者转诊至提供肾脏替代治疗的儿科中心。
我们报告的患者的总体临床过程与先前报道的TARS2相关的COXPD21病例非常吻合，特别是在该疾病的神经和发育方面。然而,我们指出我们患者的广泛性肾小管病和CKD的早期发生是COXPD21的不典型肾脏受累。此外,这是COXPD21患者的甲状腺功能减退症和甲状旁腺功能减退症的首例报告.
