Mauri Alessia, Saielli Laura Assunta, Alfei Enrico, Iascone Maria, Marchetti Daniela, Cattaneo Elisa, Di Lauro Anna, Antonelli Laura, Alberti Luisella, Bonaventura Eleonora, Veggiotti Pierangelo, Spaccini Luigina, Cereda Cristina
Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
Center of Functional Genomics and Rare Diseases, Buzzi Children's Hospital, Milan, Italy.
Front Genet. 2023 Mar 2;14:1077625. doi: 10.3389/fgene.2023.1077625. eCollection 2023.
Menkes disease is an X-linked recessive condition caused by mutations in the gene, which leads to severe copper deficiency. Aminoacylase-1 deficiency is a rare inborn error of metabolism caused by homozygous or compound heterozygous variant in the gene, characterized by increased urinary excretion of specific N-acetyl amino acids. We report an infant with neurological findings such as seizures, neurodevelopmental delay and hypotonia. Metabolic screening showed low serum copper and ceruloplasmin, and increased urinary excretion of several N-acetylated amino acids. Whole-exome sequencing analysis (WES) revealed the novel variant c.3642_3649dup (p.Ala1217Aspfs*2) in the gene, leading to a diagnosis of Menkes disease, and the simultaneous presence of the homozygous variant c.1057C>T (p.Arg353Cys) causative of Aminoacylase-1 deficiency. Our patient had two rare conditions with different treatment courses but overlapping clinical features. The identified novel mutation associated with Menkes disease expands the gene spectrum.
门克斯病是一种由该基因突变引起的X连锁隐性疾病，会导致严重的铜缺乏。氨基酰化酶-1缺乏症是一种罕见的先天性代谢紊乱，由该基因的纯合或复合杂合变异引起，其特征是特定N-乙酰氨基酸的尿排泄增加。我们报告了一名有癫痫发作、神经发育迟缓及肌张力减退等神经系统表现的婴儿。代谢筛查显示血清铜和铜蓝蛋白水平低，几种N-乙酰化氨基酸的尿排泄增加。全外显子测序分析（WES）在该基因中发现了新的变异c.3642_3649dup（p.Ala1217Aspfs*2），从而诊断为门克斯病，同时存在导致氨基酰化酶-1缺乏症的纯合变异c.1057C>T（p.Arg353Cys）。我们的患者患有两种罕见疾病，治疗过程不同但临床特征有重叠。所鉴定的与门克斯病相关的新突变扩展了该基因谱。
