Hyperprolinemia type II (HPII) is a rare autosomal recessive disorder of proline degradation pathway due to deficiency of delta-1-pyrroline-5-carboxylate dehydrogenase. Pathogenic variants in the ALDH4A1 gene are responsible for this disorder. We here describe an 11-month-old infant with recurrent seizures refractory to multiple antiepileptic drugs. She was hospitalized in view of acute-onset encephalopathy, exacerbation of generalized seizures following an upper respiratory infection. Laboratory investigation revealed significantly elevated proline levels in dried blood spots. DNA sample of the child was subjected to a targeted next-generation sequencing gene panel for hyperprolinemias. We detected a novel nonsense homozygous variant in the ALDH4A1 gene in the child and the heterozygous variant of the same in both the parents. Based on the location of the variant i.e. in the last exon, truncated protein is expected to be expressed by skipping nonsense-mediated decay and such point-nonsense variants could be an ideal target for readthrough drugs to correct genetic defects.

高脯氨酸血症 II 型 (HPII) 是由于 delta-1-pyrroline-5-carboxylate dehydrogenase 缺乏导致的脯氨酸降解途径的一种罕见的常染色体隐性遗传疾病。ALDH4A1基因中的致病变异是导致这种疾病的原因。我们在此描述了一名 11 个月大的婴儿，其反复发作的癫痫发作对多种抗癫痫药物无效。她因急性发作性脑病住院，上呼吸道感染后全身性癫痫发作恶化。实验室调查显示干血斑中脯氨酸水平显着升高。对孩子的 DNA 样本进行了针对高脯氨酸血症的靶向下一代测序基因组。我们在ALDH4A1中检测到一种新的无意义纯合变体孩子的基因和父母双方的相同基因的杂合变体。基于变体的位置，即在最后一个外显子中，预计截短的蛋白质将通过跳过无义介导的衰变来表达，并且这种点无义变体可能是通读药物纠正遗传缺陷的理想目标。