Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation
Abstract Background TMEM199 deficiency was recently shown in four patients to cause liver disease with steatosis, elevated serum transaminases, cholesterol and alkaline phosphatase and abnormal protein glycosylation. There is no information on the long-term outcome in this disorder. Results We here...
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doaj-ab5cb8607c3e4443af5bc8049231a9fe2020-11-25T01:25:00ZengBMCOrphanet Journal of Rare Diseases1750-11722018-01-011311610.1186/s13023-017-0757-3Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylationPietro Vajro0Katarzyna Zielinska1Bobby G. Ng2Marco Maccarana3Per Bengtson4Marco Poeta5Claudia Mandato6Elisa D’Acunto7Hudson H. Freeze8Erik A. Eklund9Unit of Pediatrics, Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of SalernoDivision of Pediatrics, Lund UniversityHuman Genetics Program, Sanford Burnham Prebys Medical Discovery InstituteSection for Matrix Biology, Department of Experimental Medical Sciences, Lund UniversityDivision of Clinical Chemistry, Department of Clinical Sciences, Lund UniversityUnit of Pediatrics, Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of SalernoChildren’s Hospital “Santobono-Pausilipon”, 1st Division of PediatricsUnit of Pediatrics, Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of SalernoHuman Genetics Program, Sanford Burnham Prebys Medical Discovery InstituteDivision of Pediatrics, Lund UniversityAbstract Background TMEM199 deficiency was recently shown in four patients to cause liver disease with steatosis, elevated serum transaminases, cholesterol and alkaline phosphatase and abnormal protein glycosylation. There is no information on the long-term outcome in this disorder. Results We here present three novel patients with TMEM199-CDG. All three patients carried the same set of mutations (c.13-14delTT (p.Ser4Serfs*30) and c.92G > C (p.Arg31Pro), despite only two were related (siblings). One mutation (c.92G > C) was described previously whereas the other was deemed pathogenic due to its early frameshift. Western Blot analysis confirmed a reduced level of TMEM199 protein in patient fibroblasts and all patients showed a similar glycosylation defect. The patients presented with a very similar clinical and biochemical phenotype to the initial publication, confirming that TMEM199-CDG is a non-encephalopathic liver disorder. Two of the patients were clinically assessed over two decades without deterioration. Conclusion A rising number of disorders affecting Golgi homeostasis have been published over the last few years. A hallmark finding is deficiency in protein glycosylation, both in N- and O-linked types. Most of these disorders have signs of both liver and brain involvement. However, the present and the four previously reported patients do not show encephalopathy but a chronic, non-progressive (over decades) liver disease with hypertransaminasemia and steatosis. This information is crucial for the patient/families and clinician at diagnosis, as it distinguishes it from other Golgi homeostasis disorders, in having a much more favorable course.http://link.springer.com/article/10.1186/s13023-017-0757-3CDGGlycosylationCeruloplasminTransferrinLiver diseaseTransaminase |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pietro Vajro Katarzyna Zielinska Bobby G. Ng Marco Maccarana Per Bengtson Marco Poeta Claudia Mandato Elisa D’Acunto Hudson H. Freeze Erik A. Eklund |
spellingShingle |
Pietro Vajro Katarzyna Zielinska Bobby G. Ng Marco Maccarana Per Bengtson Marco Poeta Claudia Mandato Elisa D’Acunto Hudson H. Freeze Erik A. Eklund Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation Orphanet Journal of Rare Diseases CDG Glycosylation Ceruloplasmin Transferrin Liver disease Transaminase |
author_facet |
Pietro Vajro Katarzyna Zielinska Bobby G. Ng Marco Maccarana Per Bengtson Marco Poeta Claudia Mandato Elisa D’Acunto Hudson H. Freeze Erik A. Eklund |
author_sort |
Pietro Vajro |
title |
Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation |
title_short |
Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation |
title_full |
Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation |
title_fullStr |
Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation |
title_full_unstemmed |
Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation |
title_sort |
three unreported cases of tmem199-cdg, a rare genetic liver disease with abnormal glycosylation |
publisher |
BMC |
series |
Orphanet Journal of Rare Diseases |
issn |
1750-1172 |
publishDate |
2018-01-01 |
description |
Abstract Background TMEM199 deficiency was recently shown in four patients to cause liver disease with steatosis, elevated serum transaminases, cholesterol and alkaline phosphatase and abnormal protein glycosylation. There is no information on the long-term outcome in this disorder. Results We here present three novel patients with TMEM199-CDG. All three patients carried the same set of mutations (c.13-14delTT (p.Ser4Serfs*30) and c.92G > C (p.Arg31Pro), despite only two were related (siblings). One mutation (c.92G > C) was described previously whereas the other was deemed pathogenic due to its early frameshift. Western Blot analysis confirmed a reduced level of TMEM199 protein in patient fibroblasts and all patients showed a similar glycosylation defect. The patients presented with a very similar clinical and biochemical phenotype to the initial publication, confirming that TMEM199-CDG is a non-encephalopathic liver disorder. Two of the patients were clinically assessed over two decades without deterioration. Conclusion A rising number of disorders affecting Golgi homeostasis have been published over the last few years. A hallmark finding is deficiency in protein glycosylation, both in N- and O-linked types. Most of these disorders have signs of both liver and brain involvement. However, the present and the four previously reported patients do not show encephalopathy but a chronic, non-progressive (over decades) liver disease with hypertransaminasemia and steatosis. This information is crucial for the patient/families and clinician at diagnosis, as it distinguishes it from other Golgi homeostasis disorders, in having a much more favorable course. |
topic |
CDG Glycosylation Ceruloplasmin Transferrin Liver disease Transaminase |
url |
http://link.springer.com/article/10.1186/s13023-017-0757-3 |
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