Expanding the genotype-phenotype spectrum of ISCA2-related multiple mitochondrial dysfunction syndrome-cavitating leukoencephalopathy and prolonged survival

Neurogenetics - Tập 21 - Trang 243-249 - 2020
Tamar Gur Hartman1,2, Keren Yosovich3, Hila Gur Michaeli3, Lubov Blumkin1,4, Liat Ben-Sira4,5, Dorit Lev3,4, Tally Lerman-Sagie1,4, Ayelet Zerem1,4,6
1Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel
2School of Psychological Sciences, Tel Aviv University, Tel Aviv, Israel
3Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel
4Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
5Pediatric Radiology Unit, TASMC, Tel Aviv, Israel
6Pediatric Neurology Unit, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

Tóm tắt

Iron-sulfur cluster assembly 2 (ISCA2)-related multiple mitochondrial dysfunction syndrome 4 (MMDS4) is a fatal autosomal recessive mitochondrial leukoencephalopathy. The disease typically manifests with rapid neurodevelopmental deterioration during the first months of life leading to a vegetative state and early death. MRI demonstrates a demyelinating leukodystrophy. We describe an eleven-year-old boy with a milder phenotype of ISCA2 related disorder manifesting as: normal early development, acute infantile neurologic deterioration leading to stable spastic quadriparesis, optic atrophy and mild cognitive impairment. The first MRI demonstrated a diffuse demyelinating leukodystrophy. A sequential MRI revealed white matter rarefaction with well-delineated cysts. The patient harbors two novel bi-allelic variants (p.Ala2Asp and p.Pro138Arg) in ISCA2 inherited from heterozygous carrier parents. This report expands the clinical spectrum of ISCA2-related disorders to include a milder phenotype with a longer life span and better psychomotor function and cavitating leukodystrophy on MRI. We discuss the possible genetic explanation for the different presentation.

Tài liệu tham khảo

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