PDF(Pubmed)
Abstract：
Carbonic anhydrase VA (CA-VA) deficiency is a rare cause of hyperammonemia caused by biallelic mutations in CA5A. Most patients present with hyperammonemic encephalopathy in early infancy to early childhood, and patients usually have no further recurrence of hyperammonemia with a favorable outcome. This retrospective cohort study reports 18 patients with CA-VA deficiency caused by homozygosity for a founder mutation, c.59G>A p.(Trp20*) in CA5A. The reported patients show significant intrafamilial and interfamilial variability, and display atypical clinical features. Two adult patients were asymptomatic, 7/18 patients had recurrent hyperammonemia, 7/18 patients developed variable degree of developmental delay, 9/11 patients had hyperCKemia, and 7/18 patients had failure to thrive. Microcephaly was seen in three patients and one patient developed a metabolic stroke. The same variant had been reported already in a single South Asian patient presenting with neonatal hyperammonemic encephalopathy and subsequent development of seizures and developmental delay. This report highlights the limitations of current understanding of the pathomechanisms involved in this disorder, and calls for further evaluation of the possible role of genetic modifiers in this condition.
摘要：
碳酸酐酶VA（CA-VA）缺乏症是由CA5A的双等位基因突变引起的高氨血症的罕见原因。大多数患者在婴儿早期至儿童早期出现高血氨脑病，患者通常没有高氨血症的进一步复发，预后良好。这项回顾性队列研究报告了18例因创始人突变纯合性导致的CA-VA缺乏症患者，c.59G>CA5A中的Ap.（Trp20*）。报告的患者表现出显著的家族内和家族间变异性，并显示不典型的临床特征。两名成年患者无症状，7/18患者反复出现高氨血症，7/18患者出现不同程度的发育迟缓，9/11患者患有高CK血症，和7/18患者未能茁壮成长。在三名患者中发现了小头畸形，一名患者发生了代谢性中风。在一名患有新生儿高氨血症性脑病，随后出现癫痫发作和发育迟缓的南亚患者中，已经报道了相同的变异。本报告强调了目前对这种疾病所涉及的病理机制的理解的局限性。并呼吁进一步评估遗传修饰剂在这种情况下的可能作用。
