Abstract
Hepatocerebral mitochondrial DNA depletion syndromes are classically considered diseases of early childhood, typically affecting the liver, peripheral, and central nervous systems with a rapidly progressive course. Evidence is emerging that initial symptom onset can extend into adulthood, though few such cases have been reported. We describe a 25-year-old woman who presented initially with secondary amenorrhea, followed by a megaloblastic anemia, lactic acidosis, leukoencephalopathy, progressive peripheral neuropathy, and liver cirrhosis. An apparently homozygous P98L mutation was identified in MPV17, a gene associated with a lethal infantile neurohepatopathy. Homozygosity for the same allele was recently reported in a man with a similar hepatic and neurologic phenotype. This is the first clinical report of an adult female with this disorder, and the first to describe amenorrhea and megaloblastic anemia as likely associated symptoms.
Competing interests: None declared
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Acknowledgment
The authors would like to thank Robert B. Layzer, MD, from the University of California, San Francisco, for his help in evaluating this patient.
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Communicated by: Gregory Enns
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Summary
Mitochondrial DNA depletion syndromes can present in adulthood with multisystem involvement, including amenorrhea and megaloblastic anemia as newly described in this report.
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Bryce Mendelsohn has received consulting fees from Counsyl.
Neil Mehta, Bilal Hameed, Melike Pekmezci, Seymour Packman, and Jeffrey Ralph declare that they have no conflicts of interest.
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 studies described in this report are of a retrospective nature regarding clinical care and do not require informed consent. No identifying information is provided. No animals were used in this study.
Drs. Mendelsohn, Mehta, Hameed, Packman, and Ralph all clinically evaluated the patient and provided critical insight into medical and diagnostic management. Dr. Pekmezci reviewed and reported the pathology samples described herein. All authors contributed to and critically reviewed the manuscript.
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Mendelsohn, B.A., Mehta, N., Hameed, B., Pekmezci, M., Packman, S., Ralph, J. (2013). Adult-Onset Fatal Neurohepatopathy in a Woman Caused by MPV17 Mutation. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Case and Research Reports, Volume 13. JIMD Reports, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_267
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DOI: https://doi.org/10.1007/8904_2013_267
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