Shu Jianbo, Zhi Xiufang, Chen Jing, Lei Meifang, Zheng Jie, Sheng Wenchao, Zhang Chunhua, Li Dong, Cai Chunquan
Tianjin Children's Hospital (Children's Hospital of Tianjin University), Tianjin, China.
Tianjin Pediatric Research Institute, Tianjin, China.
Front Pediatr. 2022 Feb 21;10:838341. doi: 10.3389/fped.2022.838341. eCollection 2022.
β-Ureidopropionase deficiency is a rare autosomal recessive disease affecting the last step of pyrimidine degradation. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder caused by genetic defects in mitochondrial DNA.
One 8-year-old boy presented with dizziness, vomiting, and convulsions. The gas chromatography-mass spectrometry results suggested β-ureidopropionase deficiency. The whole-exome sequencing results revealed homozygous missense variant c.977G>A (p.R326Q) in . However, the patient presented with persistent hyperlactacidemia and metabolic acidosis, which did not correspond to the classic features of β-ureidopropionase deficiency. Combined with the manifestations of developmental delay, poor academic performance, and poor sports stamina, whole-mitochondrial-genome sequencing was performed. The results exhibited the variant m.3243A>G of gene. The level of heterogeneity was 65% in the patient and 17.8% in his mother. Eventually, the final diagnosis of β-ureidopropionase deficiency combined with MELAS syndrome was made.
The report about β-ureidopropionase deficiency caused by a nuclear gene variant and MELAS syndrome caused by a mitochondrial gene variant coexisting in the same patient enriches the clinical study of these two rare diseases.
β-脲基丙酸酶缺乏症是一种罕见的常染色体隐性疾病，影响嘧啶降解的最后一步。线粒体脑肌病伴乳酸酸中毒和卒中样发作（MELAS）综合征是一种由线粒体DNA基因缺陷引起的罕见遗传性疾病。
一名8岁男孩出现头晕、呕吐和惊厥。气相色谱-质谱分析结果提示β-脲基丙酸酶缺乏症。全外显子组测序结果显示 基因存在纯合错义变异c.977G>A（p.R326Q）。然而，该患者出现持续性高乳酸血症和代谢性酸中毒，这与β-脲基丙酸酶缺乏症的典型特征不符。结合发育迟缓、学业成绩差和运动耐力差的表现，进行了线粒体全基因组测序。结果显示 基因存在m.3243A>G变异。患者的异质性水平为65%，其母亲为17.8%。最终，确诊为β-脲基丙酸酶缺乏症合并MELAS综合征。
关于同一患者中由核基因变异引起的β-脲基丙酸酶缺乏症和由线粒体基因变异引起的MELAS综合征并存的报道，丰富了这两种罕见疾病的临床研究。
