Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
PardisGene Co., Tehran, Iran.
Ir J Med Sci. 2024 Feb;193(1):449-456. doi: 10.1007/s11845-023-03452-0. Epub 2023 Jul 31.
Aminoacylase-1 deficiency (ACY1D) is an autosomal recessive rare inborn error of metabolism, which is caused by disease-causing variants in the ACY1. This disorder is characterized by increased urinary excretion of specific N-acetyl amino acids. Affected individuals demonstrate heterogeneous clinical manifestations which are primarily neurologic problems. In neuroimaging, corpus callosum hypoplasia, cerebellar vermis atrophy, and delayed myelination of cerebral white matter have been reported.
Finding disease-causing variant and expanding imaging findings in a patient with persistent basal ganglia involvement.
Whole-exome sequencing was performed in order to identify disease-causing variants in an affected 5-year-old male patient who presented with neurologic regression superimposed on neurodevelopmental delay following a febrile illness. He had inability to walk, cognitive impairment, speech delay, febrile-induced seizures, truncal hypotonia, moderate to severe generalized dystonia, and recurrent metabolic decompensation.
All metabolic tests were normal except for a moderate metabolic acidosis following febrile illnesses. The results of serial brain magnetic resonance imaging (MRI) at ages 1 and 4.5 years revealed persistent bilateral and symmetric abnormal signals in basal ganglia mainly caudate and globus pallidus nuclei with progression over time in addition to a mild supratentorial atrophy. A homozygous missense variant [NM_000666.3: c.1057C>T; p.(Arg353Cys)] was identified in the ACY1, consistent with aminoacylase-1 deficiency. Variant confirmation in patient and segregation analysis in his family were performed using Sanger sequencing.
Our findings expanded the phenotype spectrum of ACY1-related neurodegeneration by demonstrating persistent basal ganglia involvement and moderate to severe generalized dystonia.
氨基己酸酶-1 缺乏症（ACY1D）是一种常染色体隐性遗传的罕见代谢性遗传病，由 ACY1 中的致病变异引起。该疾病的特征是特定的 N-乙酰氨基酸尿排泄增加。受影响的个体表现出异质性的临床表现，主要是神经系统问题。在神经影像学中，已经报道了胼胝体发育不良、小脑蚓部萎缩和脑白质髓鞘化延迟。
在一名持续性基底节受累的患者中寻找致病变异并扩展影像学发现。
对一名 5 岁男性患者进行全外显子组测序，该患者在发热性疾病后出现神经发育迟缓叠加的神经退行性进展。他无法行走、认知障碍、言语延迟、发热性癫痫、躯干性张力减退、中重度全身性肌张力障碍和反复代谢性失代偿。
除发热性疾病后出现中度代谢性酸中毒外，所有代谢检查均正常。1 岁和 4.5 岁时的连续脑部磁共振成像（MRI）结果显示双侧和对称的基底节异常信号，主要累及尾状核和苍白球核，随着时间的推移逐渐进展，此外还有轻度幕上萎缩。在 ACY1 中发现了一个纯合错义变异 [NM_000666.3: c.1057C>T; p.(Arg353Cys)]，与氨基己酸酶-1 缺乏症一致。使用 Sanger 测序对患者和其家族中的变异进行了确认和分离分析。
我们的发现通过证明持续性基底节受累和中重度全身性肌张力障碍，扩展了 ACY1 相关神经退行性变的表型谱。
