Abstract
Intermittent hypoglycemia has been described in association with Alpers’ syndrome, a disorder caused by mutations in the mitochondrial DNA polymerase gamma gene. In some patients hypoglycemia may define the initial disease presentation well before the onset of the classical Alpers’ triad of psychomotor retardation, intractable seizures, and liver failure. Correlating with the genotype, POLG pathogenicity is a result of increased mitochondrial DNA mutability, and mitochondrial DNA depletion resulting in energy deficient states. Hypoglycemia therefore could be secondary to any metabolic pathway affected by ATP deficiency. Although it has been speculated that hypoglycemia is due to secondary fatty acid oxidation defects or abnormal gluconeogenesis, the exact underlying etiology is still unclear. Here we present detailed studies on carbohydrate metabolism in an Alpers’ patient who presented initially exclusively with intermittent episodes of hypoglycemia and ketosis. Our results do not support a defect in gluconeogenesis or fatty acid oxidation as the cause of hypoglycemia. In contrast, studies performed on liver biopsy suggested abnormal glycogenolysis. This is shown via decreased activities of glycogen brancher and debrancher enzymes with normal glycogen structure and increased glycogen on histology of the liver specimen. To our knowledge, this is the first report documenting abnormalities in glycogen metabolism in a patient with Alpers’ syndrome.
Competing interests: None declared
The first two authors contributed equally
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Acknowledgments
MS was partially supported by grants from Haley’s Wish Foundation. We thank Karen Leydiker and Leighann Sremba for editing the manuscript.
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Communicated by: Wolfgang Sperl
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Synopsis
Hypoglycemia associated with mitochondrial disease mimicking glycogen storage disease may be underrecognized or underreported and may manifest prior to the onset of typical mitochondrial disease symptoms like seizures or liver failure.
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Conflict of Interest
Mariella Simon declares that she has been partially supported by Hailey’s wish foundation, a charitable foundation interested in supporting causes concerning mitochondrial disease.
Richard Chang declares that he has no conflict of interest.
Deeksha Bali declares that she has no conflict of interest.
Lee-Jun Wong declares that she has no conflict of interest.
Ying Peng declares that she has no conflict of interest.
Jose Abdenur declares that he has no conflict of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). The study does not qualify as human subject research since the patient is deceased and there are no subject identifiers.
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This article does not contain any studies with animal subjects performed by the any of the authors.
Contributions of Individual Authors
Mariella Simon wrote the abstract, introduction, and discussion.
Richard Chang wrote the case report and cared for the patient.
Deeksha Bali was in charge of enzyme studies for glycogen storage disease.
Lee-Jun Wong was in charge of POLG testing.
Ying Peng oversaw neurological testing and cared for the patient.
Jose E. Abdenur designed clinical and laboratory testing strategy and planned and edited the manuscript.
All authors have reviewed the final version of the manuscript.
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Simon, M., Chang, R.C., Bali, D.S., Wong, LJ., Peng, Y., Abdenur, J.E. (2013). Abnormalities in Glycogen Metabolism in a Patient with Alpers’ Syndrome Presenting with Hypoglycemia. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports, Volume 14. JIMD Reports, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_280
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DOI: https://doi.org/10.1007/8904_2013_280
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