Elsevier

Brain and Development

Volume 43, Issue 4, April 2021, Pages 590-595
Brain and Development

Case Report
Peripheral nerves are involved in hypomyelinating leukodystrophy-3 caused by a homozygous AIMP1 variant

https://doi.org/10.1016/j.braindev.2020.12.008Get rights and content

Abstract

Introduction

Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their correct tRNAs. Bi-allelic truncating variants in the AIMP1 gene have been associated with hypomyelinating leukodystrophy-3 (HLD3; MIM 260600), which is characterized by hypomyelination, microcephaly, seizures and decreased life expectancy. Although peripheral nerve involvement has been assumed for HLD3, no compelling evidence is available to date.

Case report

The case was a first-born Filipino male. He showed profound developmental delay, failure to thrive, and spasticity in his limbs. At three months of age he developed refractory epilepsy. Serial magnetic resonance imaging (MRIs) showed profound myelination delay and progressive cerebral atrophy. He showed abnormal nerve conduction studies. Genetic testing revealed a homozygous pathogenic variant in the AIMP1 gene (NM_004757.3: c.115C > T: p.Gln39*). The parents were heterozygous for the same variant.

Conclusion

Here, we report a patient with a homozygous nonsense AIMP1 variant showing peripheral neuropathy as well as HLD3. Our case suggests that AIMP1 plays a pivotal role in the peripheral nerve as well as the central nervous system.

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.

Section snippets

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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