Alpes–guttenloher syndrome in medical practice (clinical case)
Abstract
Alpes–Guttenloher is a rare and severe mitochondrial disease that results from depletion of mitochondrial DNA (mtDNA). Caused by mutations in the POLG1 gene. The syndrome is characterized by a triad of symptoms — progressive regression of development, severe convulsions and liver failure. The disease progresses steadily and often leads to death due to liver failure or epileptic status within four years of the onset of the disease. Treatment of epilepsy with valproic acid can lead to a rapid onset of liver failure and should be avoided. In this article we describe the case of an 8 month old baby with epilepsy and liver failure on the background of valproic acid treatment with a fatal case. The diagnosis was confirmed by molecular genetic study post mortum.The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee (LEC) of all participating institution. The informed consent of the patient was obtained for conducting the studies.
References
Alpers BJ. (1931). Diffuse progressive degeneration of the gray matter of the cerebrum. Arch Neurol Psychiatry.25: 469–505. https://doi.org/10.1001/archneurpsyc.1931.02230030027002
Bicknese AR, May W, Hickey WF, Dodson WE(1992). Early childhood hepatocerebral degeneration misdiagnosed as valproate hepatotoxicity. Ann Neurol. 32(6): 767–75. https://doi.org/10.1002/ana.410320610; PMid:1471867
Bohan TP, Helton E, McDonald I, K’nig S, Gazitt S. (2001). Effect of L-carnitine treatment for valproate/induced hepatotoxicity. Neurology. 22; 56(10): 1405–9. https://doi.org/10.1212/WNL.56.10.1405; PMid:11376200
Harding BN. (1990). Progressive neuronal degeneration of childhood with liver disease (Alpers/Huttenlocher syndrome): a personal review. J Child Neurol. 5: 273–287. https://doi.org/10.1177/088307389000500402; PMid:2246481
McFarland R, Hudson G, Taylor RW, Green SH, Hodges S et al. (2008). Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1).Arch Dis Child. 93(2): 151–3. https://doi.org/10.1136/adc.2007.122911; PMid:18208989
Naess К, Barbaro M, Bruhn H, Wibom R, Nennesmo I, von D’beln U et al. (2012). Complete Deletion of a POLG1 Allele in a Patient with Alpers Syndrome. JIMD Rep. 4: 67–73. https://doi.org/10.1007/8904_2011_73; PMid:23430898 PMCid:PMC3509876.
Naviaux RK, Nguyen KV. (2004). POLG mutations associated with Alpers syndrome and mitochondrial DNA depletion. Ann Neurol. 55: 706–712. https://doi.org/10.1002/ana.20079; PMid:15122711
Naviaux RK, Nyhan WL, Barshop BA et al. (1999). Mitochondrial DNA polymerase γ deficiency and mtDNA depletion in a child with Alpers' syndrome. Ann Neurol. 45:54–58. https://doi.org/10.1002/1531-8249(199901)45:1<54::AID-ART10>3.0.CO;2-B
Nguyen KV, Sharief FS, Chan SS, Copeland WC, Naviaux RK. (2006). Molecular diagnosis of Alpers syndrome. J Hepatol.45: 108–116. https://doi.org/10.1016/j.jhep.2005.12.026; PMid:16545482
Park S, Kang HC, Lee JS, Park YN et al. (2017). Alpers-Huttenlocher Syndrome First Presented with Hepatic Failure: Can Liver Transplantation Be Considered as Treatment Option? Pediatr Gastroenterol Hepatol Nutr. 20(4): 259–262. https://doi.org/10.5223/pghn.2017.20.4.259; PMid:29302508 PMCid:PMC5750381
Saneto RP, Cohen BH, Copeland WC, Naviaux RK (2013). Alpers-Huttenlocher syndrome. Pediatr Neurol.48(3): 167–78. https://doi.org/10.1016/j.pediatrneurol.2012.09.014; PMid:23419467 PMCid:PMC3578656.
Van Goethem G, Dermaut B, Lofgren A, Martin JJ, Van Broeckhoven C. (2001). Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet. 28(3): 211–2. https://doi.org/10.1038/90034; PMid:11431686
Wiltshire E, Davidzon G, DiMauro S, Akman HO, Sadleir L et al. (2008, Jan). Juvenile Alpers disease. Arch Neurol. 65(1): 121–4. https://doi.org/10.1001/archneurol.2007.14; PMid:18195149
Wolf NI, Rahman S, Schmitt B, Taanman JW, Duncan AJ et al. (2009). Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI features. Epilepsia. 50(6): 1596–607. https://doi.org/10.1111/j.1528-1167.2008.01877.x; PMid:19054397
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