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ISSN 2007-6452 (Print)

2022, Number 3

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Investigación en Discapacidad 2022; 8 (3)

Report of a case of Alpers-Huttenlocher syndrome associated with a heterozygous pathogenic variant in POLG

Cerecedo-Zapata CM, Alvarado-Jiménez G, Alatriste-Cequera JP

Language: Spanish
References: 22
Page: 110-114
PDF size: 163.74 Kb.


ABSTRACT

Introduction: Alpers-Huttenlocher syndrome (AHS) is an autosomal recessive inheritance condition associated with POLG, characterized by the classic triad of epilepsy refractory to treatment with a focal component, regression of psychomotor development and liver disease. We present a clinical case of a mexican proband with clinical diagnosis of AHS. Clinical case: a girl of six years six months with adequate psychomotor development until 4 years of age. Subsequently, she presents insidious muscle weakness in the lower limbs and pain and myoclonic movements in both. Subsequently, cognitive deterioration occurs, she presents flaccid dysarthria, adequate head control, no trunk control with equinus foot deformity. Electroencephalogram with multiple epileptic discharges, direct bilirubin 1.69 mg/dL, serum lactic acid 20 mg/dL, magnetic resonance of the brain without alterations. By molecular testing, it was demonstrated a heterozygous pathogenic variant in POLG (c.1433+1G>A). Conclusion: the proband presents characteristics of SAH clinically, she presents only one pathogenic variant in POLG, it is not possible to rule out the presence of non-obvious variants due to the methodology used. To our knowledge, this is the first report of Alpers syndrome in a Mexican individual.


REFERENCES

  1. Ropp PA, Copeland WC. Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase gamma. Genomics. 1996; 36 (3): 449-458.

  2. Alpers B. Diffuse progressive degeneration of the gray matter of the cerebrum. Arch NeurPsych. 1931; 25 (3): 469-505.

  3. Huttenlocher PR, Solitare GB, Adams G. Infantile diffuse cerebral degeneration with hepatic cirrhosis. Arch Neurol. 1976; 33 (3): 186-192.

  4. Nguyen KV, Sharief FS, Chan SS, Copeland WC, Naviaux RK. Molecular diagnosis of Alpers syndrome. J Hepatol. 2006; 45 (1): 108-116.

  5. Harding B, Alsanjari N, Smith S, Wiles C, Thrush D, Milles D et al. Progressive neuronal degeneration of childhood with liver disease (Alpers' disease) presenting in young adults. Journal of Neurology, Neurosurgery and Psychiatry. 1995; 58 (3): 320-325.

  6. Harding BN. Progressive neuronal degeneration of childhood with liver disease (Alpers-Huttenlocher syndrome): a personal review. J Child Neurol. 1990; 5 (4): 273-287.

  7. Wiltshire E, Davidzon G, DiMauro S, Akman HO, Sadleir L, Haas L et al. Juvenile Alpers disease. Arch Neurol. 2008; 65 (1): 121-124.

  8. Saneto RP, Cohen BH, Copeland WC, Naviaux RK. Alpers-Huttenlocher syndrome. Pediatr Neurol. 2013; 48 (3): 167-178.

  9. Cohen BH, Chinnery PF, Copeland WC. POLG-Related disorders. 2010. In: Adam MP, Everman DB, Mirzaa GM et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2022. Available in: https://www.ncbi.nlm.nih.gov/books/NBK26471/

  10. Worle H, Kohler B, Schlote W, Winkler P, Bastanier CK. Progressive cerebral degeneration of childhood with liver disease (Alpers Huttenlocher disease) with cytochrome oxidase deficiency presenting with epilepsia partialis continua as the first clinical manifestation. Clin Neuropathol. 1998; 17 (2): 63-68.

  11. Horvath R, Hudson G, Ferrari G, Fütterer N, Ahola S, Lamantea E et al. Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Brain. 2006; 129(Pt 7): 1674-1684.

  12. ncbi.nlm.nih.gov. 2022. VCV000280017.9 - ClinVar - NCBI. [On line] [Accessed 23 August 2022] Available in: https://www.ncbi.nlm.nih.gov/clinvar/variation/280017/?oq=280017&m=NM_002693.3(POLG):c.1433%201G%3EA

  13. Baralle D, Baralle M. Splicing in action: assessing disease causing sequence changes. J Med Genet. 2005; 42 (10): 737-748.

  14. Tang S, Wang J, Lee NC, Milone M, Halberg MC, Schmitt ES et al. Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and clinical spectrum. J Med Genet. 2011; 48 (10): 669-681.

  15. inegi.org.mx. 2022. [online] [Accessed 25 August 2022] Available in: https://www.inegi.org.mx/contenidos/productos/prod_serv/contenidos/espanol/bvinegi/productos/nueva_estruc/702825198039.pdf

  16. Van Goethem G, Dermaut B, Lofgren A, Martin JJ, Van Broeckhoven C. Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet. 2001; 28 (3): 211-212.

  17. omim.org. 2022. Phenotypic series - PS220110 - OMIM. [Accessed 25 August 2022] Available in: https://www.omim.org/phenotypicSeries/PS220110

  18. Von Kleist-Retzow J, Cormier-Daire V, de Lonlay P, Parfait B, Chretien D, Rustin P et al. A high rate (20%–30%) of parental consanguinity in cytochrome-oxidase deficiency. Am J Hum Genet. 1998; 63 (2): 428-435.

  19. Baertling F, Al-Murshedi F, Sánchez-Caballero L, Al-Senaidi K, Joshi NP, Venselaar H et al. Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive. Hum Mutat. 2017; 38 (6): 692-703.

  20. Lake NJ, Compton AG, Rahman S, Thorburn DR. Leigh syndrome: one disorder, more than 75 monogenic causes. Ann Neurol. 2016; 79 (2): 190-203.

  21. Van Goethem G, Lofgren A, Dermaut B, Ceuterick C, Martin JJ, Van Broeckhoven C. Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle. Hum Mutat. 2003; 22 (2): 175-176.

  22. Da Pozzo P, Rubegni A, Rufa A, Cardaioli E, Taglia I, Gallus GN, Malandrini A, Federico A. Sporadic PEO caused by a novel POLG variation and a Twinkle mutation: digenic inheritance? Neurol Sci. 2015; 36 (9): 1713-1715.




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