Las enfermedades raras (ERs) son un grupo heterogeneo de enfermedades con baja frecuencia, que afecta a 1 de cada 2.000 personas. Hay cerca de 7.000 patologias, el 80% seria de origen genetico. La mayoria son poco conocidas por el personal de salud lo que origina errores y dificultades en el diagnostico. Algunas tienen un tratamiento farmacologico especifico, los medicamentos “huerfanos“, que son terapias exclusivas de alto costo. En Chile existe poca informacion sobre frecuencia y distribucion de ERs, alguna ha sido recolectada por agrupaciones de pacientes.

Background: Mandatory fortification with folic acid (FA) was implemented in Chile in 2000. Thereafter, the rate of spina bifida decreased by 52 to 55%. Genetic abnormalities in folate metabolism may be involved in the etiology of spina bifida. Aim: To evaluate the association between myelomeningocele (MM) and c.A1298C and c.C677T polymorphisms within the coding gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) in the Chilean population. Material and Methods: These polymorphisms were genotyped in 105 patients showing isolated MM, born after the onset of FA fortification, and in their parents. The transmission disequilibrium test (TDT) was performed to evaluate alterations in the transmission of both alleles and haplotypes MTHFR polymorphism. We also evaluated the presence of parent-origin-effect (POE) of alleles using the Clayton's extension of the TDT. Results: TDT analysis showed no significant distortions in the transmission of alleles or haplotypes. Moreover, although the POE showed increased risk for maternally derived allele, this risk was not statistically significant. Conclusions: The studied variants in the MTHFR gene (c.C677T and c.A1298C) do not constitute risk factors for MM in this sample of Chilean patients and their parents.

Methylenetetrahydrofolate reductase polymorphisms as risk factors for myelomeningoceleBackground: Mandatory fortification with folic acid (FA) was implemented in Chile in 2000.Thereafter, the rate of spina bifida decreased by 52 to 55%.Genetic abnormalities in folate metabolism may be involved in the etiology of spina bifida.Aim: To evaluate the association between myelomeningocele (MM) and c.A1298C and c.C677T polymorphisms within the coding gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) in the Chilean population.Material and Methods: These polymorphisms were genotyped in 105 patients showing isolated MM, born after the onset of FA fortification, and in their parents.The transmission disequilibrium test (TDT) was performed to evaluate alterations in the transmission of both alleles and haplotypes MTHFR polymorphism.We also evaluated the presence of parent-origin-effect (POE) of alleles using the Clayton's extension of the TDT.Results: TDT analysis showed no significant distortions in the transmission of alleles or haplotypes.Moreover, although the POE showed increased risk for maternally derived allele, this risk was not statistically significant.Conclusions: The studied variants in the MTHFR gene (c.C677T and c.A1298C) do not constitute risk factors for MM in this sample of Chilean patients and their parents.(