• Mohammad Farid Mohammadi, Ali Dehghani, Kiana Zarabadi, Seyyed Mohammad Kahani, Setareh Sayyad, Mahmoud Reza Ashrafi, Morteza Heidari, Pouria Mohammadi, Masoud Garshasbi, and Ali Reza Tavasoli.
• Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
• Ir J Med Sci. 2024 Feb 1; 193 (1): 449456449-456.

BackgroundAminoacylase-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.AimsFinding disease-causing variant and expanding imaging findings in a patient with persistent basal ganglia involvement.MethodsWhole-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.ResultsAll 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.ConclusionsOur findings expanded the phenotype spectrum of ACY1-related neurodegeneration by demonstrating persistent basal ganglia involvement and moderate to severe generalized dystonia.© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.

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