TY - JOUR
T1 - Case report
T2 - ‘AARS2 leukodystrophy’
AU - Axelsen, Tobias Melton
AU - Vammen, Tzvetelina Lubenova
AU - Bak, Mads
AU - Pourhadi, Nelsan
AU - Stenør, Christian Midtgaard
AU - Grønborg, Sabine
N1 - Funding Information:
The authors wish to thank the patient and his next-of-kin as well as the reviewers of the paper.
Publisher Copyright:
© 2021
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9
Y1 - 2021/9
N2 - Background: Mitochondrial alanyl-tRNA synthetase 2 gene (AARS2) related disease is a rare genetic disorder affecting mitochondrial metabolism, leading to severe cardiac disease in infants or progressive leukodystrophy in young adults. The disease is considered ultra-rare with only 39 cases of AARS2-leukodystrophy previously reported. Case presentation: We present the case of a young man of consanguineous heritage suffering from cognitive decline and progressive spasticity as well as weakness of the proximal musculature. Utilizing MRI and whole genome sequencing, the patient was diagnosed with a homozygous AARS2 missense variant (NM_020745.3:c.650C > T; p.(Pro217Leu)) and a homozygous CAPN3 variant (NM_000070.2: c.1469G > A; p.(Arg490Gln)), both variants have previously been identified in patients suffering from AARS2 related leukodystrophy and limb-girdle muscular dystrophy, respectively. Conclusions: This case report presents a case of homozygous AARS2 leukodystrophy and serves to highlight the importance of whole genome sequencing in diagnosing rare neurological diseases as well as to add to the awareness of adult onset leukodystrophies.
AB - Background: Mitochondrial alanyl-tRNA synthetase 2 gene (AARS2) related disease is a rare genetic disorder affecting mitochondrial metabolism, leading to severe cardiac disease in infants or progressive leukodystrophy in young adults. The disease is considered ultra-rare with only 39 cases of AARS2-leukodystrophy previously reported. Case presentation: We present the case of a young man of consanguineous heritage suffering from cognitive decline and progressive spasticity as well as weakness of the proximal musculature. Utilizing MRI and whole genome sequencing, the patient was diagnosed with a homozygous AARS2 missense variant (NM_020745.3:c.650C > T; p.(Pro217Leu)) and a homozygous CAPN3 variant (NM_000070.2: c.1469G > A; p.(Arg490Gln)), both variants have previously been identified in patients suffering from AARS2 related leukodystrophy and limb-girdle muscular dystrophy, respectively. Conclusions: This case report presents a case of homozygous AARS2 leukodystrophy and serves to highlight the importance of whole genome sequencing in diagnosing rare neurological diseases as well as to add to the awareness of adult onset leukodystrophies.
KW - AARS2
KW - Adult onset leukodystrophies
KW - Case report
KW - Inborn errors of metabolism
KW - Limb-girdle muscular dystrophy
KW - Whole genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85109479469&partnerID=8YFLogxK
U2 - 10.1016/j.ymgmr.2021.100782
DO - 10.1016/j.ymgmr.2021.100782
M3 - Journal article
C2 - 34285876
AN - SCOPUS:85109479469
SN - 2214-4269
VL - 28
JO - Molecular Genetics and Metabolism Reports
JF - Molecular Genetics and Metabolism Reports
M1 - 100782
ER -