Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening
Wolman disease (WD) is a lethal disorder defined by the deficiency of the lysosomal acid lipase enzyme. Patients present with intestinal failure, malnutrition, and hepatosplenomegaly. Enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) significantly improves survival. We sought t...
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MDPI AG
2025-02-01
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| Series: | International Journal of Neonatal Screening |
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| Online Access: | https://www.mdpi.com/2409-515X/11/1/17 |
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| author | Maria Jose de Castro Lopez Fiona J. White Victoria Holmes Jane Roberts Teresa H. Y. Wu James A. Cooper Heather J. Church Gemma Petts Robert F. Wynn Simon A. Jones Arunabha Ghosh |
| author_facet | Maria Jose de Castro Lopez Fiona J. White Victoria Holmes Jane Roberts Teresa H. Y. Wu James A. Cooper Heather J. Church Gemma Petts Robert F. Wynn Simon A. Jones Arunabha Ghosh |
| author_sort | Maria Jose de Castro Lopez |
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| description | Wolman disease (WD) is a lethal disorder defined by the deficiency of the lysosomal acid lipase enzyme. Patients present with intestinal failure, malnutrition, and hepatosplenomegaly. Enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) significantly improves survival. We sought to determine the outcomes of two siblings with WD treated after the onset of symptoms (sibling 1) and presymptomatic (sibling 2). A chart review was conducted on two siblings with WD treated with ERT and DSR at 4 months of age (sibling 1) and immediately after birth (sibling 2) to determine clinical outcomes based on survival, laboratory results, growth, dietary records, and gut biopsies. Sibling 1 presented with hepatosplenomegaly and liver dysfunction and developed hemophagocytic lymphohistiocytosis despite treatment. She received a bone marrow transplant at 8 months of age but died at 13 months. Sibling 2 is alive at 16 months of age with height, weight, and MUAC above the 95th centile, fully orally fed, with no gastrointestinal symptoms, normal liver function, and normal oxysterols. Sibling 2 duodenal biopsies show normal villus architecture with no foamy macrophage infiltration. Initiation of treatment prior to the onset of symptoms can prevent clinical manifestations and increase survival. The divergent trajectory in these siblings raises the question of WD’s candidacy for newborn screening. |
| format | Article |
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| institution | OA Journals |
| issn | 2409-515X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | International Journal of Neonatal Screening |
| spelling | doaj-art-6efff26b2434491bab5dfb59cd1338ab2025-08-20T01:48:46ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2025-02-011111710.3390/ijns11010017Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn ScreeningMaria Jose de Castro Lopez0Fiona J. White1Victoria Holmes2Jane Roberts3Teresa H. Y. Wu4James A. Cooper5Heather J. Church6Gemma Petts7Robert F. Wynn8Simon A. Jones9Arunabha Ghosh10Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UKManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UKManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UKManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UKManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UKManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UKManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UKDepartment of Paediatric Histopathology, Royal Manchester Children’s Hospital, Oxford Road, Manchester M13 9WL, UKDepartment of Blood and Marrow Transplantation, Royal Manchester Children’s Hospital, Oxford Road, Manchester M13 9WL, UKManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UKManchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Oxford Road, Manchester M13 9WL, UKWolman disease (WD) is a lethal disorder defined by the deficiency of the lysosomal acid lipase enzyme. Patients present with intestinal failure, malnutrition, and hepatosplenomegaly. Enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) significantly improves survival. We sought to determine the outcomes of two siblings with WD treated after the onset of symptoms (sibling 1) and presymptomatic (sibling 2). A chart review was conducted on two siblings with WD treated with ERT and DSR at 4 months of age (sibling 1) and immediately after birth (sibling 2) to determine clinical outcomes based on survival, laboratory results, growth, dietary records, and gut biopsies. Sibling 1 presented with hepatosplenomegaly and liver dysfunction and developed hemophagocytic lymphohistiocytosis despite treatment. She received a bone marrow transplant at 8 months of age but died at 13 months. Sibling 2 is alive at 16 months of age with height, weight, and MUAC above the 95th centile, fully orally fed, with no gastrointestinal symptoms, normal liver function, and normal oxysterols. Sibling 2 duodenal biopsies show normal villus architecture with no foamy macrophage infiltration. Initiation of treatment prior to the onset of symptoms can prevent clinical manifestations and increase survival. The divergent trajectory in these siblings raises the question of WD’s candidacy for newborn screening.https://www.mdpi.com/2409-515X/11/1/17Wolman diseaseenzyme replacement therapydietary substrate reductionearly diagnosisearly treatmentnewborn screening |
| spellingShingle | Maria Jose de Castro Lopez Fiona J. White Victoria Holmes Jane Roberts Teresa H. Y. Wu James A. Cooper Heather J. Church Gemma Petts Robert F. Wynn Simon A. Jones Arunabha Ghosh Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening International Journal of Neonatal Screening Wolman disease enzyme replacement therapy dietary substrate reduction early diagnosis early treatment newborn screening |
| title | Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening |
| title_full | Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening |
| title_fullStr | Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening |
| title_full_unstemmed | Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening |
| title_short | Does Early Diagnosis and Treatment Alter the Clinical Course of Wolman Disease? Divergent Trajectories in Two Siblings and a Consideration for Newborn Screening |
| title_sort | does early diagnosis and treatment alter the clinical course of wolman disease divergent trajectories in two siblings and a consideration for newborn screening |
| topic | Wolman disease enzyme replacement therapy dietary substrate reduction early diagnosis early treatment newborn screening |
| url | https://www.mdpi.com/2409-515X/11/1/17 |
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