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Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT

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Abstract 

Guanidinoacetate methyltransferase deficiency (GAMTD) is a treatable neurodevelopmental disorder with normal or nonspecific imaging findings. Here, we reported a 14-month-old girl with GAMTD and novel findings on brain magnetic resonance imaging (MRI).

A 14-‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍month-old female patient was referred to Myelin Disorders Clinic due to onset of seizures and developmental regression following routine vaccination at 4 months of age. Brain MRI, prior to initiation of treatment, showed high signal intensity in T2-weighted imaging in bilateral thalami, globus pallidus, subthalamic nuclei, substantia nigra, dentate nuclei, central tegmental tracts in the brainstem, and posterior periventricular white matter which was masquerading for mitochondrial leukodystrophy. Basic metabolic tests were normal except for low urine creatinine; however, exome sequencing identified a homozygous frameshift deletion variant [NM_000156: c.491del; (p.Gly164AlafsTer14)] in the GAMT. Biallelic pathogenic or likely pathogenic variants cause GAMTD. We confirmed the homozygous state for this variant in the proband, as well as the heterozygote state in the parents by Sanger sequencing.

MRI features in GAMTD can mimic mitochondrial leukodystrophy. Pediatric neurologists should be aware of variable MRI findings in GAMTD since they would be misleading to other diagnoses.

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Data availability

We state that the data not provided in this article will be shared on request by email to the corresponding author from any qualified investigator for purposes of replicating procedures and results.

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Acknowledgements

We thank all participants in this research. The authors are especially thankful to the patient and his parents who took part to this study and also the personnel of the Children’s Medical Center for supporting us in this study

Funding

The National Institute for Medical Research Development (Proposal No. 983886) provided financial and logistic support for this study but had no role in study design, the collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the article for publication.

Author information

Author notes

  1. Seyedeh Atiyeh Afjei and Mohammad Farid Mohammadi contributed equally to this work.

Authors and Affiliations

  1. American University of the Caribbean School of Medicine, Pembroke Pines, USA

    Seyedeh Atiyeh Afjei

  2. Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

    Mohammad Farid Mohammadi

  3. Pediatric Neurology Division, Pediatrics Center of Excellence, Children’s Medical Center, Myelin Disorders Clinic, Tehran University of Medical Sciences, Tehran, Iran

    Elham Pourbakhtyaran, Homa Ghabeli, Roya Haghighi, Maryam Rasulinezhad, Ali Reza Tavasoli & Morteza Heidari

  4. Department of Pediatric Neurology, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Mahmoud Reza Ashrafi

  5. Department of Radiology, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Neda Pak

  6. Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, USA

    Ali Reza Tavasoli

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  1. Seyedeh Atiyeh Afjei
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Contributions

MH and SAA conceived and designed the experiments. MFM, MH, ART, and EP conducted the experiments. MH, MFM, SAA, HGH, MR, and MRA analyzed and interpreted the data. MH, RH, MRA, ART, and NP contributed reagents/materials/analysis tools. MH, SAA, and MFM wrote the paper. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Ali Reza Tavasoli or Morteza Heidari.

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Ethics approval and consent to participate

The written informed consent was obtained from the parents as legal guardians of the proband. The study protocol was approved by the local medical ethics committee of Children’s Medical Center, Tehran, Iran. The study was being performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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The authors declare no competing interests.

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Afjei, S.A., Mohammadi, M.F., Pourbakhtyaran, E. et al. Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT. Neurogenetics 24, 67–78 (2023). https://doi.org/10.1007/s10048-022-00708-2

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