摘要：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.
关键词：AARS2 ; Adult onset leukodystrophies ; Limb-girdle muscular dystrophy ; Whole genome sequencing ; Case report ; Inborn errors of metabolism ; AARS2 Mitochondrial alanyl-tRNA synthetase 2 gene ; Mt-aaRS Mitochondrial aminoacyl-tRNA synthetase ; AARS2 -L Mitochondrial alanyl-tRNA synthetase 2 gene leukodystrophy ; DARS2 Deficiency of aspartyl-tRNA ; EARS2 Deficiency of glutamate-tRNA synthetase ; MMSE Mini-Mental State Examination ; CSF Cerebrospinal fluid ; ADLs activities of daily living ; mtDNA Mitochondrial DNA ; LGMD R1 Limb-girdle muscular dystrophy R1 calpain3-related ; IEM Inborn errors of metabolism ; HDLS Hereditary Diffuse Leukodystrophy with axonal Spheroids ; ALSP Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia ; CSF1R C olony stimulating factor-1 receptor
