Pyruvate dehydrogenase deficiency in a young boy: a clinical case
- Authors: Poretskova G.Y.1, Kalinina E.A.2, Korotkova N.N2, Bolgarova O.G.2, Kuznetsova N.N.2, Gaisin S.I.1, Beschastnaya E.O.1
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Affiliations:
- Samara State Medical University
- V.D. Seredavin Samara Regional Clinical Hospital
- Issue: Vol 15, No 2 (2024)
- Pages: 98-105
- Section: Case reports
- URL: https://journals.rcsi.science/clinpractice/article/view/262735
- DOI: https://doi.org/10.17816/clinpract629443
- ID: 262735
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Abstract
BACKGROUND: Pyruvate dehydrogenase deficit is a severe hereditary mitochondrial metabolic disease characterized by impaired energy metabolism and manifested by a wide range of neurological symptoms. The difficulty in selecting therapy is due to insufficient data on the management of children with this pathology owing to death at an early age and insufficient diagnosis during life. The accurate prevalence of the disease is unknown, presumably <1 in 1,000,000, which makes it attributable to orphan diseases.
CLINICAL CASE DESCRIPTION: This article presents a case of a child with a rare neurometabolic disease pyruvate dehydrogenase complex E1 deficiency. The diagnosis was suspected after his birth based on neurological symptoms, neonatal hyperammonemia, and hyperlactatemia and confirmed after exome sequencing, where a homozygous variant of the nucleotide sequence in the PDNA1 gene (X-19359612-C-E) was determined. At the age of 2 months, he began to receive a ketogenic diet — a high-fat, low-carbohydrate dry mixture for enteral nutrition, metabolic therapy, and Vit B1 (300 mg/day). The article presents indicators of biochemical blood testing, acid-base state of blood, and dynamics of the neurological picture during the period of observation of the patient.
CONCLUSION: Early diagnosis and initiation of therapy is crucial for the physical and neuropsychiatric development of children with this pathology. Despite the lack of highly effective etiotropic treatment, in some cases, an improvement in the clinical course is observed with the use of thiamine preparations and adherence to a ketogenic diet.
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##article.viewOnOriginalSite##About the authors
Galina Yu. Poretskova
Samara State Medical University
Email: g.yu.poreckova@samsmu.ru
ORCID iD: 0000-0002-3131-1368
SPIN-code: 2271-4588
MD, PhD, Associate Professor
Russian Federation, SamaraElena A. Kalinina
V.D. Seredavin Samara Regional Clinical Hospital
Email: calinialena@yandex.ru
ORCID iD: 0009-0006-9466-4562
SPIN-code: 4109-3011
Russian Federation, Samara
Natalia N Korotkova
V.D. Seredavin Samara Regional Clinical Hospital
Email: n_kotkova2001@mail.ru
ORCID iD: 0009-0007-0581-2760
Russian Federation, Samara
Olga G. Bolgarova
V.D. Seredavin Samara Regional Clinical Hospital
Email: bolgarova2707@yandex.ru
ORCID iD: 0009-0001-2055-9122
Russian Federation, Samara
Natalia N. Kuznetsova
V.D. Seredavin Samara Regional Clinical Hospital
Email: natazina09@yandex.ru
ORCID iD: 0009-0001-8892-3058
Russian Federation, Samara
Shamil I. Gaisin
Samara State Medical University
Email: guspie@yandex.ru
ORCID iD: 0009-0001-2639-5501
Russian Federation, Samara
Elizaveta O. Beschastnaya
Samara State Medical University
Author for correspondence.
Email: e.o.bechastnaya@samsmu.ru
ORCID iD: 0009-0002-2499-9675
Russian Federation, Samara
References
- DeBrosse SD, Okajima K, Zhang S, et al. Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: Lack of correlation with genotype. Mol Genet Metab. 2012;107(3):394–402. doi: 10.1016/j.ymgme.2012.09.001
- Horga A, Woodward CE, Mills A, et al. Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair. Hum Genet. 2019;138(11-12):1313–1322. EDN: NTSHMV doi: 10.1007/s00439-019-02075-9
- Blass JP, Avigan J, Uhlendorf BV. A defect in pyruvate decarboxylase in a child with an intermittent movement disorder. J Clin Invest. 1970;49(3):423–432. doi: 10.1172/JCI106251
- Imbard A, Butron A, Veco S, et al. Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural consequences of new amino acid substitutions in the E1 protein. Mol Genet Metab. 2011;104(4):507–516. doi: 10.1016/j.ymgme.2011.08.008
- Adeva M, González-Lucán M, Seco M, Donapetry C. Enzymes involved in l-lactate metabolism in humans. Mitochondrion. 2013;13(6):615–629. EDN: YDORFL doi: 10.1016/j.mito.2013.08.011
- Brown GK, Otero LJ, LeGris M, Brown RM. Pyruvate dehydrogenase deficiency. J Med Genet. 1994;31(11):875–879. doi: 10.1136/jmg.31.11.875
- Kubiak GM, Tomasik AR, Bartus K, et al. Lactate in cardiogenic shock: Current understanding and clinical implications. J Physiol Pharmacol. 2018;69(1):15–21. doi: 10.26402/jpp.2018.1.02
- Hayashida K, Suzuki M, Yonemoto N, et al.; SOS-KANTO 2012 Study Group. Early lactate clearance is associated with improved outcomes in patients with postcardiac arrest syndrome: A prospective, multicenter observational study (SOS-KANTO 2012 Study). Crit Care Med. 2017;45(6): e559–e566. doi: 10.1097/CCM.0000000000002307
- Li X, Yang Y, Zhang B, et al. Lactate metabolism in human health and disease. Signal Transduct Target Ther. 2022;7(1):305. EDN: VGHXFC doi: 10.1038/s41392-022-01151-3
- Vilarino L, Nogueira S. PCR in the analysis of clinical samples: Prenatal and postnatal diagnosis of congenital metabolic disorders. Methods of Mol Biol. 2017;(1620):213–224. doi: 10.1007/978-1-4939-7060-5_15
- Pavlu-Pereira H, Silva MJ, Florindo C, et al. Pyruvate dehydrogenase complex deficiency: Updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese patients. Orphanet J Rare Dis. 2020;15(1):298. EDN: RLSIBL doi: 10.1186/s13023-020-01586-3
- Sperl V, Fleuren R, Freisinger P., et al. The spectrum of pyruvate oxidation defects in the diagnosis of mitochondrial disorders. J Inherit Metab Dis. 2015;38(3):391–403. doi: 10.1007/s10545-014-9787-3
- Bedoyan JK, Hecht L, Zhang S, et al. A novel null mutation in the pyruvate dehydrogenase phosphatase catalytic subunit gene (PDP1) causing pyruvate dehydrogenase complex deficiency. JIMD Rep. 2019;48(1):26–35. doi: 10.1002/jmd2.12054
- Maj MC, Cameron JM, Robinson BH. Pyruvate dehydrogenase phosphatase deficiency: Orphan disease or an under-diagnosed condition? Mol Cell Endocrinol. 2006;249(1-2):1–9. doi: 10.1016/j.mce
- Gupta N, Rutledge C. Pyruvate dehydrogenase complex deficiency: An unusual cause of recurrent lactic acidosis in a paediatric critical care unit. J Crit Care Med (Targu Mures). 2019;5(2):71–75. doi: 10.2478/jccm-2019-0012
- Giribaldi G, Doria-Lamba L, Biancheri R, et al. Intermittent-relapsing pyruvate dehydrogenase complex deficiency: A case with clinical, biochemical, and neuroradiological reversibility. Dev Med Child Neurol. 2012;54(5):472–476. doi: 10.1111/j.1469-8749.2011.04151.x
- Barnerias C, Saudubray JM, Touati G, et al. Pyruvate dehydrogenase complex deficiency: four neurological phenotypes with differing pathogenesis. Dev Med Child Neurol. 2010;52(2):1–9. doi: 10.1111/j.1469-8749.2009.03541.x
- Egloff C, Eldin de Pecoulas A, Mechler C, et al. Prenatal sonographic description of fetuses affected by pyruvate dehydrogenase or pyruvate carboxylase deficiency. Prenat Diagn. 2018. doi: 10.1002/pd.5282
- Meldau S, Fratter C, Bhengu LN, et al. Pitfalls of relying on genetic testing only to diagnose inherited metabolic disorders in non-western populations: 5 Cases of pyruvate dehydrogenase deficiency from South Africa. Mol Genet Metab Rep. 2020;(24): 100629. doi: 10.1016/j.ymgmr.2020.100629
- Karissa P, Simpson T, Dawson SP, et al. Comparison between dichloroacetate and phenylbutyrate treatment for pyruvate dehydrogenase deficiency. Br J Biomed Sci. 2022;(79):10382. EDN: TYRFOF doi: 10.3389/bjbs.2022.10382
- Sofou K, Dahlin M, Hallböök T, et al. Ketogenic diet in pyruvate dehydrogenase complex deficiency: Short- and long-term outcomes. J Inherit Metab Dis. 2017;40(2):237–245. doi: 10.1007/s10545-016-0011-5
- Scholl-Bürgi S, Höller A, Pichler K, et al. Ketogenic diets in patients with inherited metabolic disorders. J Inherit Metab Dis. 2015;38(4):765–773. doi: 10.1007/s10545-015-9872-2
- Ogawa E, Hishiki T, Hayakawa N, et al. Ketogenic diet in action: Metabolic profiling of pyruvate dehydrogenase deficiency. Mol Genet Metab Rep. 2023;(35):100968. EDN: NTRUWY doi: 10.1016/j.ymgmr.2023.100968
- Elnageh KM, Gaitonde MK. Effect of a deficiency of thiamine on brain pyruvate dehydrogenase: Enzyme assay by three different methods. J Neurochem. 1988;51(5):1482–1489. doi: 10.1111/j.1471-4159.1988.tb01115.x