Abstract
Mucolipidosis type IV (MLIV; OMIM 252,650) is an autosomal recessive lysosomal disorder caused by mutations in MCOLN1. MLIV causes psychomotor impairment and progressive vision loss. The major hallmarks of postnatal brain MRI are hypomyelination and thin corpus callosum. Human brain pathology data is scarce and demonstrates storage of various inclusion bodies in all neuronal cell types. The current study describes novel fetal brain MRI and neuropathology findings in a fetus with MLIV. Fetal MRI was performed at 32 and 35 weeks of gestation due to an older sibling with spastic quadriparesis, visual impairment and hypomyelination. Following abnormal fetal MRI results, the parents requested termination of pregnancy according to Israeli regulations. Fetal autopsy was performed after approval of the high committee for pregnancy termination. A genetic diagnosis of MLIV was established in the fetus and sibling. Sequential fetal brain MRI showed progressive curvilinear hypointensities on T2-weighted images in the frontal deep white matter and a thin corpus callosum. Fetal brain pathology exhibited a thin corpus callosum and hypercellular white matter composed of reactive astrocytes and microglia, multifocal white matter abnormalities with mineralized deposits, and numerous aggregates of microglia with focal intracellular iron accumulation most prominent in the frontal lobes. This is the first description in the literature of brain MRI and neuropathology in a fetus with MLIV. The findings demonstrate prenatal white matter involvement with significant activation of microglia and astrocytes and impaired iron metabolism.
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The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
All other authors participated in writing the paper and contributed to further revisions, suggestions and drafts. All authors read and approved the final manuscript.
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DK performed the autopsy. YF performed the placental pathology. LBS and ZL interpreted the MRI scans. NA and DL performed the genetic evaluation. AZ, NV, and TLS analyzed the clinical, radiological and pathological data and wrote the paper. RS, YG and AM reviewed and interpreted the data.
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Zerem, A., Ben-Sira, L., Vigdorovich, N. et al. White matter abnormalities and iron deposition in prenatal mucolipidosis IV- fetal imaging and pathology. Metab Brain Dis 36, 2155–2167 (2021). https://doi.org/10.1007/s11011-021-00742-3
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DOI: https://doi.org/10.1007/s11011-021-00742-3