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.

中文翻译：

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扩大与ISCA2相关的多发性线粒体功能障碍综合征导致白质脑病的基因型-表型谱，并延长生存期。

铁硫簇组装体2（ISCA2）相关的线粒体功能障碍综合症4（MMDS4）是致命的常染色体隐性线粒体白质脑病。该病通常在生命的最初几个月表现为快速的神经发育恶化，从而导致植物状态和早期死亡。MRI表现为脱髓鞘性白细胞营养不良。我们描述了一个ISCA2表型较轻的11岁男孩相关疾病表现为：正常早期发育，急性婴儿神经系统恶化导致稳定的痉挛性四肢瘫痪，视神经萎缩和轻度认知障碍。首次MRI显示弥漫性脱髓鞘性白细胞营养不良。连续MRI显示白质稀疏，囊肿清晰。该患者在ISCA2中携带了两个新的双等位基因变体（p.Ala2Asp和p.Pro138Arg），这些变体是从杂合子携带者父母那里继承的。该报告扩大了与ISCA2相关的疾病的临床范围，使其包括具有更长寿命，更好的精神运动功能和MRI上的空化性白细胞营养不良的较温和的表型。我们讨论了不同表现形式的可​​能的遗传学解释。