[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-441694-105":59,"doc-detail-441694-en":134},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":127,"head_meta":129,"extra_data":131,"updated_unix":133},105,"en","genomic-autopsy-in-neonatal-onset-mucopolysaccharidosis-type-vii-key-for-diagnosis-and-future-planning","Genomic autopsy in neonatal-onset mucopolysaccharidosis type VII: Key for diagnosis and future planning","","Genomic autopsy identifies the genetic cause of neonatal-onset mucopolysaccharidosis type VII when classic clinical signs are absent due to early lethality. A neonate with fetal hydrops and severe respiratory failure died on day 1, without typical skeletal or visceral findings. Autopsy revealed marked edema, effusions, pulmonary hypoplasia, and foamy histiocytes. Despite negative histochemical and immunostaining results, trio whole-exome sequencing detected compound heterozygous pathogenic variants in GUSB, enabling definitive diagnosis and informing future planning.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/genomic-autopsy-in-neonatal-onset-mucopolysaccharidosis-type-vii-key-for-diagnosis-and-future-planning/441694/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/genomic-autopsy-in-neonatal-onset-mucopolysaccharidosis-type-vii-key-for-diagnosis-and-future-planning/441694.png","ImageObject",300,407,{"name":92,"@type":93},"Sarah ","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"Why is diagnosis of neonatal-onset MPS VII difficult in this case?","Question",{"text":112,"@type":113},"Diagnosis was challenging because the neonate died early and typical MPS VII manifestations such as hepatosplenomegaly and skeletal dysplasia were not observed. Fetal edema also has nonspecific prenatal presentations.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What key autopsy finding prompted genetic testing?",{"text":117,"@type":113},"Foamy histiocytes were observed in the liver and spleen, suggesting a lysosomal storage disorder. This finding led to further genetic testing even when typical staining markers were negative.",{"name":119,"@type":110,"acceptedAnswer":120},"What genetic variants confirmed MPS type VII?",{"text":121,"@type":113},"Trio whole-exome sequencing identified two pathogenic GUSB variants: a novel maternally inherited frameshift deletion (NM_000181.4:c.1838_1839del) and a paternally inherited known missense variant (NM_000181.4:c.1618G>A, p.(Glu540Lys)).",{"name":123,"@type":110,"acceptedAnswer":124},"How does the genomic autopsy approach support future planning?",{"text":125,"@type":113},"By combining conventional autopsy with genetic techniques, the approach provides an early definitive diagnosis when symptoms are atypical. This enables appropriate consideration of enzyme replacement therapy when survival is expected and informs risk management for future pregnancies.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},441694,1790962592,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"language":143,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":144,"faqs":145,"seo_title":146,"seo_description":67,"update_tm":147,"read_time":39,"preview_page_count":4},962085320529,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","DOI: 10. 1111/ped.70299  \nC L I N I CA L N O T E  \nGenomic autopsy in neonatal-onset mucopolysaccharidosis type VII: Key for diagnosis and future planning  \nTakashi Okuno1,2  | Masamichi Ikawa2 | Miori Yuasa1 | Akifumi Muramoto3 | Li Fu4 | Naomichi Matsumoto4,5,6,7  | Atsushi Watanabe8  \n1Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, Fukui, Japan 2Department of Medical Genetics, University of Fukui Hospital, Fukui, Japan 3Department of Tumor Pathology, University of Fukui Hospital, Fukui, Japan  \n4Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan  \n5Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan 6Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, Japan 7Medical Genome Center, National Center of Neurology and Psychiatry, Kodaira, Japan 8Division of Clinical Genetics, Kanazawa University Hospital, Kanazawa, Japan  \nCorrespondence  \nTakashi Okuno, Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 233, Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.  \nEmail: [okuno@u-fukui.ac.jp](okuno@u-fukui.ac.jp)  \nKEYWORDS  \nfetal hydrops, genomic autopsy, lysosomal storage disorder, mucopolysaccharidosis VII, prenatal diagnosis  \nMucopolysaccharidosis (MPS) type VII (OMIM 253220), also known as Sly syndrome, is a rare lysosomal storage disorder caused by β-glucuronidase deficiency, resulting in glycosaminoglycan accumulation.1 Patients with MPS VII show skeletal deformities, cardiac valve abnormalities, and developmental delays. Due to the rarity of neonatal-onset cases, early diagnosis is challenging but essential for proper management.  \nWe present the case of a neonate born to a Japanese couple (a 32-year-old male and a 37-year-old female [G2P0110]). Fetal ascites was detected at 17 weeks of gestation and worsened by 20 weeks of gestation. Ultrasound confirmed fetal hydrops (Figure 1a). At 31 weeks of gestation, a cesarean section was performed due to nonreassuring fetal status. The neonate had a birthweight of 2300 g and bilateral pleural effusions, massive ascites, and severe respiratory failure caused by pulmonary hypoplasia. Despite intensive care, including mechanical ventilation and nitric oxide therapy, the neonate died on day 1. Due to early lethality and generalized edema, typical MPS VII features such as hepatosplenomegaly and skeletal dysplasia were not observed. The first pregnancy was terminated at 21 weeks of gestation due to fetal  \nhydrops. Both pregnancies exhibited similar complications, suggesting a possible connection.  \nAutopsy showed severe subcutaneous edema, pleural and peritoneal effusions, and pulmonary hypoplasia (Figure 1b) . Histopathological evaluation revealed foamy histiocytes in the liver and spleen (Figure 1c) . Toluidine blue staining for acidic mucopolysaccharides and CD68, an indicator of activated macrophages, was negative (Figure 1d,e) . With foamy histiocytes suggesting a lysosomal storage disorder, further genetic testing was performed, despite the absence of acidic mucopolysaccharides or activated macrophages. Chromosome analysis revealed a normal karyotype (46,XX) . Trio whole-exome sequencing using parental blood samples and preserved DNA identified two pathogenic variants in the GUSB gene (a novel NM_000181.4:c.1838_ 1839del p.(Arg613Thrfs*19) of maternal origin and a known variant, NM_000181.4:c. 1618G>A p.(Glu540Lys),2 of paternal origin) . The diagnosis was MPS type VII with a compound heterozygous mutation in the GUSB gene. The c. 1618G>A mildly reduced enzymatic activity.2 The novel c.1838_ 1839del frameshift variant is located within a region predicted to escape nonsense-mediated mRNA  \nThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, ","cbCaibQhF12q6dDG","https://ap.wps.com/l/cbCaibQhF12q6dDG","pdf",484903,"English","# Case presentation\n## Prenatal findings and clinical course\n## Autopsy and histopathology\n# Genetic testing and diagnosis\n# Clinical implications and future planning","[{\"question\":\"Why is diagnosis of neonatal-onset MPS VII difficult in this case?\",\"answer\":\"Diagnosis was challenging because the neonate died early and typical MPS VII manifestations such as hepatosplenomegaly and skeletal dysplasia were not observed. Fetal edema also has nonspecific prenatal presentations.\"},{\"question\":\"What key autopsy finding prompted genetic testing?\",\"answer\":\"Foamy histiocytes were observed in the liver and spleen, suggesting a lysosomal storage disorder. This finding led to further genetic testing even when typical staining markers were negative.\"},{\"question\":\"What genetic variants confirmed MPS type VII?\",\"answer\":\"Trio whole-exome sequencing identified two pathogenic GUSB variants: a novel maternally inherited frameshift deletion (NM_000181.4:c.1838_1839del) and a paternally inherited known missense variant (NM_000181.4:c.1618G\\u003eA, p.(Glu540Lys)).\"},{\"question\":\"How does the genomic autopsy approach support future planning?\",\"answer\":\"By combining conventional autopsy with genetic techniques, the approach provides an early definitive diagnosis when symptoms are atypical. This enables appropriate consideration of enzyme replacement therapy when survival is expected and informs risk management for future pregnancies.\"}]","Genomic autopsy in neonatal-onset mucopolysaccharidosis type VII: Key for diagnosis and future planning | PDF",1790697091]