Profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type IXɑ2 secondary to a de novo pathogenic variant in PHKA2
The phenotype of individuals with glycogen storage disease (GSD) IX appears to be highly variable, even within subtypes. Features include short stature, fasting hypoglycemia with ketosis, hepatomegaly, and transaminitis. GSD IXɑ2 is caused by hemizygous pathogenic variants in PHKA2, and results in d...
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Elsevier
2021-06-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426921000598 |
| _version_ | 1818647508625129472 |
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| author | J. Andres Morales Christina G. Tise Amrita Narang Paul C. Grimm Gregory M. Enns Chung U. Lee |
| author_facet | J. Andres Morales Christina G. Tise Amrita Narang Paul C. Grimm Gregory M. Enns Chung U. Lee |
| author_sort | J. Andres Morales |
| collection | DOAJ |
| description | The phenotype of individuals with glycogen storage disease (GSD) IX appears to be highly variable, even within subtypes. Features include short stature, fasting hypoglycemia with ketosis, hepatomegaly, and transaminitis. GSD IXɑ2 is caused by hemizygous pathogenic variants in PHKA2, and results in deficiency of the phosphorylase kinase enzyme, particularly in the liver. Like other GSDs, GSD IXɑ2 can present with hypoglycemia and post-prandial lactic acidosis, but has never been reported in a newborn, nor with lactic acidosis as the presenting feature. Here we describe the clinical presentation and course of a newborn boy with profound neonatal lactic and metabolic acidosis, renal tubulopathy, and sensorineural hearing loss (SNHL) diagnosed with GSD IXɑ2 through exome sequencing. Review of the literature suggests this case represents an atypical and severe presentation of GSD IXɑ2 and proposes expansion of the phenotype to include neonatal lactic acidosis and renal tubulopathy. |
| first_indexed | 2024-12-17T01:03:39Z |
| format | Article |
| id | doaj.art-086ffee666ff41be99e530bde744348d |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-17T01:03:39Z |
| publishDate | 2021-06-01 |
| publisher | Elsevier |
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| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-086ffee666ff41be99e530bde744348d2022-12-21T22:09:21ZengElsevierMolecular Genetics and Metabolism Reports2214-42692021-06-0127100765Profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type IXɑ2 secondary to a de novo pathogenic variant in PHKA2J. Andres Morales0Christina G. Tise1Amrita Narang2Paul C. Grimm3Gregory M. Enns4Chung U. Lee5Department of Pediatrics, Division of Medical Genetics, Stanford University, United States of America; Corresponding author at: Department of Pediatrics, Division of Medical Genetics, Stanford University, 300 Pasteur Drive, H-315, Stanford, CA 94305-5208, United States of America.Department of Pediatrics, Division of Medical Genetics, Stanford University, United States of AmericaDepartment of Pediatrics, Division of Gastroenterology, Stanford University, United States of AmericaDepartment of Pediatrics, Division of Nephrology, Stanford University, United States of AmericaDepartment of Pediatrics, Division of Medical Genetics, Stanford University, United States of AmericaDepartment of Pediatrics, Division of Medical Genetics, Stanford University, United States of AmericaThe phenotype of individuals with glycogen storage disease (GSD) IX appears to be highly variable, even within subtypes. Features include short stature, fasting hypoglycemia with ketosis, hepatomegaly, and transaminitis. GSD IXɑ2 is caused by hemizygous pathogenic variants in PHKA2, and results in deficiency of the phosphorylase kinase enzyme, particularly in the liver. Like other GSDs, GSD IXɑ2 can present with hypoglycemia and post-prandial lactic acidosis, but has never been reported in a newborn, nor with lactic acidosis as the presenting feature. Here we describe the clinical presentation and course of a newborn boy with profound neonatal lactic and metabolic acidosis, renal tubulopathy, and sensorineural hearing loss (SNHL) diagnosed with GSD IXɑ2 through exome sequencing. Review of the literature suggests this case represents an atypical and severe presentation of GSD IXɑ2 and proposes expansion of the phenotype to include neonatal lactic acidosis and renal tubulopathy.http://www.sciencedirect.com/science/article/pii/S2214426921000598Glycogen storage disorder type IXGSD IXɑ2PHKA2Sensorineural hearing lossNeonatal lactic acidosisRenal tubulopathy |
| spellingShingle | J. Andres Morales Christina G. Tise Amrita Narang Paul C. Grimm Gregory M. Enns Chung U. Lee Profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type IXɑ2 secondary to a de novo pathogenic variant in PHKA2 Molecular Genetics and Metabolism Reports Glycogen storage disorder type IX GSD IXɑ2 PHKA2 Sensorineural hearing loss Neonatal lactic acidosis Renal tubulopathy |
| title | Profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type IXɑ2 secondary to a de novo pathogenic variant in PHKA2 |
| title_full | Profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type IXɑ2 secondary to a de novo pathogenic variant in PHKA2 |
| title_fullStr | Profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type IXɑ2 secondary to a de novo pathogenic variant in PHKA2 |
| title_full_unstemmed | Profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type IXɑ2 secondary to a de novo pathogenic variant in PHKA2 |
| title_short | Profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type IXɑ2 secondary to a de novo pathogenic variant in PHKA2 |
| title_sort | profound neonatal lactic acidosis and renal tubulopathy in a patient with glycogen storage disease type ixɑ2 secondary to a de novo pathogenic variant in phka2 |
| topic | Glycogen storage disorder type IX GSD IXɑ2 PHKA2 Sensorineural hearing loss Neonatal lactic acidosis Renal tubulopathy |
| url | http://www.sciencedirect.com/science/article/pii/S2214426921000598 |
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