Identificación de una familia afectada por enfermedad de Fabry, un llamado urgente al diagnóstico temprano
Palabras clave:
enfermedad de Fabry, alfa-galactosidasa, enfermedades por almacenamiento lisosomal, examen genético
Resumen
La enfermedad de Fabry (EF) es un trastorno de depósito lisosomal ligado al cromosoma X, causado por variantes en el gen GLA. Su deficiencia enzimática genera acumulación de globotriaosilceramida, provocando compromiso multisistémico progresivo. El diagnóstico se confirma mediante análisis molecular, aunque su acceso en países en desarrollo es aún limitado.
Se reporta un varón de 33 años con: manifestaciones cardiacas, gastrointestinales, oftalmológicas, dermatológicas, renales y neurológicas; diagnosticado con EF (variante patogénica p.Arg227Gln). No recibió terapia de reemplazo enzimático por falta de disponibilidad en Perú y falleció a los 37 años por complicaciones cardiacas y renales. El tamizaje familiar en cascada identificó 31 portadores adicionales, con síntomas frecuentes como: acroparestesias, hipohidrosis y angioqueratomas.
Este es el primer caso descrito de EF en Junín, Perú. El estudio resalta la necesidad de diagnóstico precoz, disponibilidad terapéutica y tamizaje familiar, para mejorar el pronóstico y reducir la mortalidad asociada a esta enfermedad rara.
Citas
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2. Duro G, Zizzo C, Cammarata G, Burlina A, Burlina A, Polo G, et al. Mutations in the GLA gene and LysoGb3: Is it really Anderson-Fabry disease?. Int J Mol Sci [Internet]. 2018 [cited 2024 Jun 10];19(12):3726. Available from: https://pubmed.ncbi.nlm.nih.gov/30477121/
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5. Oliveira JP, Ferreira S. Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype- phenotype correlations. Appl Clin Genet [Internet]. 2019 [cited 2024 Jun 10]; 12:35–50. Available from: https://pubmed.ncbi.nlm.nih.gov/30881085/
6. Cainelli F, Argandykov D, Kaldarbekov D, Mukarov M, Phuong LTT, Germain DP. Case report: First two identified cases of fabry disease in Central Asia. Front Genet [Internet]. 2021 [cited 2024 Jun 10]; 12:657824. Available from: https://pubmed.ncbi.nlm.nih.gov/33986771/
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9. Germain DP, Altarescu G, Barriales-Villa R, Mignani R, Pawlaczyk K, Pieruzzi F, et al. An expert consensus on practical clinical recommendations and guidance for patients with classic fabry disease. Mol Genet Metab [Internet]. 2022 [cited 2024 Jun 10];137(1–2):49–61. Available from: https://pubmed.ncbi.nlm.nih.gov/35926321/
10. Anania M, Pieruzzi F, Giacalone I, Trezzi B, Marsana EM, Roggero L, et al. Identification of four new mutations in the GLA gene associated with Anderson–Fabry disease. Int J Mol Sci [Internet]. 2025 [cited 2025 Jun 10];26(2):473. Available from: https://pubmed.ncbi.nlm.nih.gov/39859188/
11. Rigoldi M, Concolino D, Morrone A, Pieruzzi F, Ravaglia R, Furlan F, et al. Intrafamilial phenotypic variability in four families with Anderson-Fabry disease. Clin Genet [Internet]. 2014 [cited 2024 Jun 10];86(3):258–63. Available from: https://pubmed.ncbi.nlm.nih.gov/23980562/ Subscription required
12. Ferreira Tátá C, Massas M, Pinto F, Caçador N, Silva AL. Fabry disease: A atypical presentation. Cureus [Internet]. 2021 [cited 2024 Jun 10];13(10): e18708. Available from: https://doi.org/10.7759/cureus.18708
13. Vardarli I, Rischpler Ch, Herrmann K, Weidemann F. Diagnosis and screening of patients with fabry disease. Ther Clin Risk Manag [Internet]. 2020 [cited 2024 Jun 10]; 16:551–8. Available from: https://pubmed.ncbi.nlm.nih.gov/32606714/
14. Silva CAB, Moura-Neto JA, Dos Reis MA, Vieira Neto OM, Barreto FC. Renal manifestations of Fabry disease: A narrative review. Can J Kidney Health Dis [Internet]. 2021 [cited 2024 Jun 10]; 8:2054358120985627. Available from: https://pubmed.ncbi.nlm.nih.gov/33786192/
15. Izhar R, Borriello M, La Russa A, Di Paola R, De A, Capasso G, et al. Fabry disease in women: Genetic basis, available biomarkers, and clinical manifestations. Genes (Base) [Internet]. 2023 [cited 2024 Jun 10];15(1):37. Available from: https://pubmed.ncbi.nlm.nih.gov/38254927/
16. Lenders M, Brand E. Fabry disease: The current treatment landscape. Drugs [Internet]. 2021 [cited 2024 Jun 10];81(6):635–45. Available from: https://pubmed.ncbi.nlm.nih.gov/33721270/
2. Duro G, Zizzo C, Cammarata G, Burlina A, Burlina A, Polo G, et al. Mutations in the GLA gene and LysoGb3: Is it really Anderson-Fabry disease?. Int J Mol Sci [Internet]. 2018 [cited 2024 Jun 10];19(12):3726. Available from: https://pubmed.ncbi.nlm.nih.gov/30477121/
3. Guaigua López SM, Guamán Castillo CA, Zambrano Sangurima MS, Campoverde Cárdenas AD. Enfermedad de Fabry. Una enfermedad renal crónica. RECIMUNDO [Internet]. 2022 [citado 10 Jun 2024];6(4):279–87. Disponible en: https://doi.org/10.26820/recimundo/6.(4).octubre.2022.279-287
4. Bernardes TP, Foresto RD, Kirsztajn GM. Fabry disease: genetics, pathology, and treatment. Rev Assoc Med Bras [Internet]. 2020 [citado 10 Jun 2024];66(Suppl 1):10–6. Disponible en: https://doi.org/10.1590/1806-9282.66.S1.10
5. Oliveira JP, Ferreira S. Multiple phenotypic domains of Fabry disease and their relevance for establishing genotype- phenotype correlations. Appl Clin Genet [Internet]. 2019 [cited 2024 Jun 10]; 12:35–50. Available from: https://pubmed.ncbi.nlm.nih.gov/30881085/
6. Cainelli F, Argandykov D, Kaldarbekov D, Mukarov M, Phuong LTT, Germain DP. Case report: First two identified cases of fabry disease in Central Asia. Front Genet [Internet]. 2021 [cited 2024 Jun 10]; 12:657824. Available from: https://pubmed.ncbi.nlm.nih.gov/33986771/
7. Mehta A, Hughes DA. Fabry disease. Synonyms: Alpha-Galactosidase A deficiency, Anderson-Fabry disease. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 2024. [cited 2024 Jun 10]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK1292/
8. Giugliani R, Niu DM, Ramaswami U, West M, Hughes D, Kampmann Ch, et al. A 15-year perspective of the fabry outcome survey. J inborn errors metab screen [Internet]. 2016 [cited 2024 Jun 10];4:1-12. Available from: https://www.scielo.br/j/jiems/a/F59fgPvBBJkyHvJTvKv3T5L/?lang=en
9. Germain DP, Altarescu G, Barriales-Villa R, Mignani R, Pawlaczyk K, Pieruzzi F, et al. An expert consensus on practical clinical recommendations and guidance for patients with classic fabry disease. Mol Genet Metab [Internet]. 2022 [cited 2024 Jun 10];137(1–2):49–61. Available from: https://pubmed.ncbi.nlm.nih.gov/35926321/
10. Anania M, Pieruzzi F, Giacalone I, Trezzi B, Marsana EM, Roggero L, et al. Identification of four new mutations in the GLA gene associated with Anderson–Fabry disease. Int J Mol Sci [Internet]. 2025 [cited 2025 Jun 10];26(2):473. Available from: https://pubmed.ncbi.nlm.nih.gov/39859188/
11. Rigoldi M, Concolino D, Morrone A, Pieruzzi F, Ravaglia R, Furlan F, et al. Intrafamilial phenotypic variability in four families with Anderson-Fabry disease. Clin Genet [Internet]. 2014 [cited 2024 Jun 10];86(3):258–63. Available from: https://pubmed.ncbi.nlm.nih.gov/23980562/ Subscription required
12. Ferreira Tátá C, Massas M, Pinto F, Caçador N, Silva AL. Fabry disease: A atypical presentation. Cureus [Internet]. 2021 [cited 2024 Jun 10];13(10): e18708. Available from: https://doi.org/10.7759/cureus.18708
13. Vardarli I, Rischpler Ch, Herrmann K, Weidemann F. Diagnosis and screening of patients with fabry disease. Ther Clin Risk Manag [Internet]. 2020 [cited 2024 Jun 10]; 16:551–8. Available from: https://pubmed.ncbi.nlm.nih.gov/32606714/
14. Silva CAB, Moura-Neto JA, Dos Reis MA, Vieira Neto OM, Barreto FC. Renal manifestations of Fabry disease: A narrative review. Can J Kidney Health Dis [Internet]. 2021 [cited 2024 Jun 10]; 8:2054358120985627. Available from: https://pubmed.ncbi.nlm.nih.gov/33786192/
15. Izhar R, Borriello M, La Russa A, Di Paola R, De A, Capasso G, et al. Fabry disease in women: Genetic basis, available biomarkers, and clinical manifestations. Genes (Base) [Internet]. 2023 [cited 2024 Jun 10];15(1):37. Available from: https://pubmed.ncbi.nlm.nih.gov/38254927/
16. Lenders M, Brand E. Fabry disease: The current treatment landscape. Drugs [Internet]. 2021 [cited 2024 Jun 10];81(6):635–45. Available from: https://pubmed.ncbi.nlm.nih.gov/33721270/
