A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia.
Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illn...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-11-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4230727?pdf=render |
| _version_ | 1819104444364619776 |
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| author | Asmaa Mamoune Michel Bahuau Yamina Hamel Valérie Serre Michele Pelosi Florence Habarou Marie-Ange Nguyen Morel Bertrand Boisson Sabrina Vergnaud Mai Thao Viou Luc Nonnenmacher Monique Piraud Patrick Nusbaum Joseph Vamecq Norma Romero Chris Ottolenghi Jean-Laurent Casanova Pascale de Lonlay |
| author_facet | Asmaa Mamoune Michel Bahuau Yamina Hamel Valérie Serre Michele Pelosi Florence Habarou Marie-Ange Nguyen Morel Bertrand Boisson Sabrina Vergnaud Mai Thao Viou Luc Nonnenmacher Monique Piraud Patrick Nusbaum Joseph Vamecq Norma Romero Chris Ottolenghi Jean-Laurent Casanova Pascale de Lonlay |
| author_sort | Asmaa Mamoune |
| collection | DOAJ |
| description | Aldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease. |
| first_indexed | 2024-12-22T02:06:27Z |
| format | Article |
| id | doaj.art-3473475ac66b4e78b0e843eda9d685cc |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-22T02:06:27Z |
| publishDate | 2014-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-3473475ac66b4e78b0e843eda9d685cc2022-12-21T18:42:31ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-11-011011e100471110.1371/journal.pgen.1004711A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia.Asmaa MamouneMichel BahuauYamina HamelValérie SerreMichele PelosiFlorence HabarouMarie-Ange Nguyen MorelBertrand BoissonSabrina VergnaudMai Thao ViouLuc NonnenmacherMonique PiraudPatrick NusbaumJoseph VamecqNorma RomeroChris OttolenghiJean-Laurent CasanovaPascale de LonlayAldolase A deficiency has been reported as a rare cause of hemolytic anemia occasionally associated with myopathy. We identified a deleterious homozygous mutation in the ALDOA gene in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. The aldolase A deficiency was rescued by arginine supplementation in vitro but not by glycerol, betaine or benzylhydantoin, three other known chaperones, suggesting that arginine-mediated rescue operated by a mechanism other than protein chaperoning. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines, and reduced by dexamethasone. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a treatment for this severe disease.http://europepmc.org/articles/PMC4230727?pdf=render |
| spellingShingle | Asmaa Mamoune Michel Bahuau Yamina Hamel Valérie Serre Michele Pelosi Florence Habarou Marie-Ange Nguyen Morel Bertrand Boisson Sabrina Vergnaud Mai Thao Viou Luc Nonnenmacher Monique Piraud Patrick Nusbaum Joseph Vamecq Norma Romero Chris Ottolenghi Jean-Laurent Casanova Pascale de Lonlay A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia. PLoS Genetics |
| title | A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia. |
| title_full | A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia. |
| title_fullStr | A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia. |
| title_full_unstemmed | A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia. |
| title_short | A thermolabile aldolase A mutant causes fever-induced recurrent rhabdomyolysis without hemolytic anemia. |
| title_sort | thermolabile aldolase a mutant causes fever induced recurrent rhabdomyolysis without hemolytic anemia |
| url | http://europepmc.org/articles/PMC4230727?pdf=render |
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