Hyperprolinemia Type I and II are genetic metabolic disorders caused by disrupted proline degradation. It has been suggested that hyperprolinemia is associated with increased risk of developmental and mental disorders but detailed information on the psychiatric phenotype in hyperprolinemic patients is limited. Following PRISMA guidelines, we carried out a systematic review to clarify psychiatric phenotypes in patients with hyperprolinemia. We screened 1753 studies and included 35 for analysis, including 20 case reports and 15 case–control and cohort studies. From these studies, a common psychiatric phenotype is observed with a high prevalence of developmental delay, intellectual disability, autism spectrum disorders, and psychosis spectrum disorders. In most cases, a genetic cause of hyperprolinemia was known, these included mutations in the PRODH and ALDH4A1 genes and deletions of chromosome 22q11.2. No evidence for a biochemical phenotype-clinical phenotype correlation was found; that is, no association between higher proline levels and specific psychiatric phenotypes was observed. This suggests that genomic and environmental factors are likely to contribute to clinical outcomes. More studies are needed to clarify whether hyperprolinemia is a primary causal factor underlying the increased risk of developing psychiatric disorders seen in patients with hyperprolinemia, or whether hyperprolinemia and psychiatric disorders are both consequences of a shared underlying mechanism.

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与高脯氨酸血症相关的精神病学表型：系统评价

I 型和 II 型高脯氨酸血症是由脯氨酸降解中断引起的遗传代谢紊乱。有人提出高脯氨酸血症与发育障碍和精神障碍的风险增加有关，但有关高脯氨酸血症患者精神表型​​的详细信息有限。根据 PRISMA 指南，我们进行了系统评价，以阐明高脯氨酸血症患者的精神表型。我们筛选了 1753 项研究，包括 35 项进行分析，包括 20 份病例报告和 15 份病例对照和队列研究。从这些研究中，观察到一种常见的精神病表型，即发育迟缓、智力残疾、自闭症谱系障碍和精神病谱系障碍的高发病率。在大多数情况下，已知高脯氨酸血症的遗传原因，包括PRODH和ALDH4A1基因和染色体 22q11.2 的缺失。没有发现生化表型-临床表型相关的证据；也就是说，没有观察到较高的脯氨酸水平与特定的精神表型之间存在关联。这表明基因组和环境因素可能有助于临床结果。需要更多的研究来阐明高脯氨酸血症是否是导致高脯氨酸血症患者发生精神疾病风险增加的主要原因，或者高脯氨酸血症和精神疾病是否都是共同潜在机制的后果。