RESUMEN
Complete resistance to vitamin K antagonists is a rare but serious condition. It can complicate therapeutic management, especially when direct oral anticoagulants cannot be used. Some single mutations in the VKORC1 gene have been identified in patients partially or completely resistant to vitamin K antagonists. We report the cases of two women in their fifties who presented an unexplained peripheral venous thrombosis. The aetiological assessment did not show any abnormalities. Genetic testing showed that both patients had the VKORC1 5417 GG genotype. The VKORC1 3673 genotype was GG in case 1 and GA in case 2. The two patients showed complete resistance to vitamin K antagonists which required a change in treatment with favourable outcomes. Our goal is to offer optimal care guided by a literature review.
RESUMEN
BACKGROUND: Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal recessive disease caused by the deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The purpose of this study was to analyze the GALNS mutations and the haplotypes associated. METHODS: Mutation screening of the GALNS gene was performed by direct sequence analysis using DNA samples from 15 unrelated Tunisian MPS IVA patients. We also analyzed the haplotypes associated with the novel mutation and with the other reported GALNS mutations. RESULTS: We have identified an unreported missense mutation p.D288G (c.863A > G) in one patient, the most frequently c.120 + 1G > A (IVS1 + 1G > A) mutation in eleven MPS IVA patients and three previously reported mutations p.G66R, p.A85T and p.R386C on the other MPS IVA patients. All the studied patients were homozygous for these identified mutations. Bioinformatics analysis predicted the novel mutation as being probably pathogenic. These findings with the unobserved p.D288G mutation in controls subjects, suggested that it is a disease-causing mutation, which was correlated with the severe phenotype observed in the patients. We have found that the two GALNS unreported and reported mutations, respectively p.D288G and p.R386C, were associated with a common and specific haplotype. CONCLUSION: Our results were in agreement with previous reports from Tunisia, suggesting, on one hand the genotype/phenotype correlations in MPS IVA patients and the other hand the haplotype analyses were useful for determination of mutation origin in Tunisian population.
