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

• 影响指数: 3.017
• 发表时间: 10 2020
• 来源期刊: Neurogenetics
• DOI: 10.1007/s10048-020-00611-8
• PMID: 32424628
• 文章类型: Case Reports
• 中科院分区: Q4
• 方向: 医学
• 作者列表: Hartman TG,Yosovich K,Michaeli HG,Blumkin L,Ben-Sira L,Lev D,Lerman-Sagie T,Zerem A

关键词: Leukodystrophy; Multiple mitochondrial dysfunction syndrome; Spastic quadriparesis; White matter rarefaction

Mesh: Alleles; Brain / diagnostic imaging; Child; DNA, Mitochondrial / genetics; Exome; Genetic Association Studies; Genetic Variation; Heterozygote; Humans; Iron-Sulfur Proteins / genetics; Leukoencephalopathies / genetics; Magnetic Resonance Imaging / methods; Male; Mitochondrial Diseases / genetics; Mutation; Phenotype

Abstract

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.