Case ReportPeripheral nerves are involved in hypomyelinating leukodystrophy-3 caused by a homozygous AIMP1 variant
Introduction
Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the mammalian multi-tRNA synthetase complex [1]. AIMP1 is important in ligating tRNAs to their cognate amino acids, but it has several other functions including axonal growth, cytokine activity, and interactions with N-acetylaspartic acid in ribosomal tRNA synthetase complexes [2]. Bi-allelic truncating variants in the AIMP1 gene cause hypomyelinating leukodystrophy-3 (HLD3; MIM260600), characterized by early neurodegeneration, hypomyelination, cerebral atrophy, progressive microcephaly and epilepsy [3], [4], [5], [6], [7], [8], [9]. Homozygous missense variants have been associated with intellectual disability, either with or without neurodegeneration, but showing a milder neuroimaging phenotype or Charcot-Marie-Tooth disease (CMT) [10], [11], [12]. Thus, while peripheral nerve involvement in HLD3 has been assumed, there has been no compelling evidence to date. This report shows peripheral neuropathy in an HLD3 patient.
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Case report
The case was a male, first-born child to healthy Filipino parents. His parents were nonconsanguineous and had no relevant medical history. He was born by spontaneous vaginal delivery at 37 gestational weeks. At birth, his weight, length and head circumference were 2140 g (−1.7 standard deviation [SD]), 47.5 cm [0 SD], and 30 cm [−1.9 SD], respectively. At birth he had a left preauricular tag, left inguinal hernia, unstable oxygenation, and feeding difficulty, which required one month of
Discussion
HLD3 is characterized by early infantile onset of neuronal developmental delay with decreased myelination in the central nervous system and peripheral spasticity [3]. The phenotype of our patient is very similar with those previously reported with truncating variants (Table 2). This is the first report using nerve conduction studies to describe an HLD3 patient with peripheral neuropathy. The right median motor nerve conduction studies showed no conduction block or temporal dispersion, but
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
We are grateful to the patient and his family for participating in this study.
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