Mitochondrial depletion syndrome type 3: the Lebanese variant
Introduction: Mitochondrial DNA depletion syndrome type 3 is an emerging disorder linked to variants in the deoxyguanosine kinase gene, which encodes for mitochondrial maintenance. This autosomal recessive disorder is frequent in the Middle East and North Africa. Diagnosis is often delayed due to th...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-06-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1215083/full |
| _version_ | 1797792459556651008 |
|---|---|
| author | Marianne Majdalani Nadine Yazbeck Lamis El Harake Jinane Samaha Pascale E. Karam |
| author_facet | Marianne Majdalani Nadine Yazbeck Lamis El Harake Jinane Samaha Pascale E. Karam |
| author_sort | Marianne Majdalani |
| collection | DOAJ |
| description | Introduction: Mitochondrial DNA depletion syndrome type 3 is an emerging disorder linked to variants in the deoxyguanosine kinase gene, which encodes for mitochondrial maintenance. This autosomal recessive disorder is frequent in the Middle East and North Africa. Diagnosis is often delayed due to the non-specificity of clinical presentation with cerebro-hepatic deterioration. The only therapeutic option is liver transplantation, although the value of this remains debatable.Methods: We describe the clinical, biochemical, and molecular profiles of Lebanese patients with this rare disorder. We also present a review of all cases from the Middle East and North Africa.Results: All Lebanese patients share a unique mutation, unreported in other populations. Almost half of patients worldwide originate from the Middle East and North Africa, with cases reported from only 7 of the 21 countries in this region. Clinical presentation is heterogeneous, with early-onset neurological and hepatic signs. Liver failure and lactic acidosis are constants. Several variants can be identified in each population; a unique c.235C>T p. (Gln79*) pathogenic variant is found in Lebanese patients. Outcome is poor, with death before 1 year of age.Conclusion: The pathogenic nonsense variant c.235C>T p. (Gln79*) in the deoxyguanosine kinase gene may be considered a founder mutation in Lebanon. Further genotypic delineation of this devastating disorder in populations with high consanguinity rates is needed. |
| first_indexed | 2024-03-13T02:34:29Z |
| format | Article |
| id | doaj.art-a89c4c557b3b468aa080432dc66b03e6 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-13T02:34:29Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-a89c4c557b3b468aa080432dc66b03e62023-06-29T09:44:29ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-06-011410.3389/fgene.2023.12150831215083Mitochondrial depletion syndrome type 3: the Lebanese variantMarianne Majdalani0Nadine Yazbeck1Lamis El Harake2Jinane Samaha3Pascale E. Karam4Division of Pediatric Intensive Care Unit, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, LebanonDivision of Gastroenterology, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, LebanonFaculty of Medicine, American University of Beirut, Beirut, LebanonInherited Metabolic Diseases Program, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, LebanonInherited Metabolic Diseases Program, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, LebanonIntroduction: Mitochondrial DNA depletion syndrome type 3 is an emerging disorder linked to variants in the deoxyguanosine kinase gene, which encodes for mitochondrial maintenance. This autosomal recessive disorder is frequent in the Middle East and North Africa. Diagnosis is often delayed due to the non-specificity of clinical presentation with cerebro-hepatic deterioration. The only therapeutic option is liver transplantation, although the value of this remains debatable.Methods: We describe the clinical, biochemical, and molecular profiles of Lebanese patients with this rare disorder. We also present a review of all cases from the Middle East and North Africa.Results: All Lebanese patients share a unique mutation, unreported in other populations. Almost half of patients worldwide originate from the Middle East and North Africa, with cases reported from only 7 of the 21 countries in this region. Clinical presentation is heterogeneous, with early-onset neurological and hepatic signs. Liver failure and lactic acidosis are constants. Several variants can be identified in each population; a unique c.235C>T p. (Gln79*) pathogenic variant is found in Lebanese patients. Outcome is poor, with death before 1 year of age.Conclusion: The pathogenic nonsense variant c.235C>T p. (Gln79*) in the deoxyguanosine kinase gene may be considered a founder mutation in Lebanon. Further genotypic delineation of this devastating disorder in populations with high consanguinity rates is needed.https://www.frontiersin.org/articles/10.3389/fgene.2023.1215083/fullDGUOKmitochondrial depletionmtDNA maintenance defectsMENAneonatal liver failurelactic acidosis |
| spellingShingle | Marianne Majdalani Nadine Yazbeck Lamis El Harake Jinane Samaha Pascale E. Karam Mitochondrial depletion syndrome type 3: the Lebanese variant Frontiers in Genetics DGUOK mitochondrial depletion mtDNA maintenance defects MENA neonatal liver failure lactic acidosis |
| title | Mitochondrial depletion syndrome type 3: the Lebanese variant |
| title_full | Mitochondrial depletion syndrome type 3: the Lebanese variant |
| title_fullStr | Mitochondrial depletion syndrome type 3: the Lebanese variant |
| title_full_unstemmed | Mitochondrial depletion syndrome type 3: the Lebanese variant |
| title_short | Mitochondrial depletion syndrome type 3: the Lebanese variant |
| title_sort | mitochondrial depletion syndrome type 3 the lebanese variant |
| topic | DGUOK mitochondrial depletion mtDNA maintenance defects MENA neonatal liver failure lactic acidosis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1215083/full |
| work_keys_str_mv | AT mariannemajdalani mitochondrialdepletionsyndrometype3thelebanesevariant AT nadineyazbeck mitochondrialdepletionsyndrometype3thelebanesevariant AT lamiselharake mitochondrialdepletionsyndrometype3thelebanesevariant AT jinanesamaha mitochondrialdepletionsyndrometype3thelebanesevariant AT pascaleekaram mitochondrialdepletionsyndrometype3thelebanesevariant |