A novel p.Gly417Valfs*12 mutation in the MTTP gene causing abetalipoproteinemia: Presentation of the first patient in Mexico and analysis of the previously reported cases

摘要

Background Our aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature. Methods We performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature. Results Our patient is a six‐year‐old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non‐classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat‐soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10?years of age have an increased risk for presenting clinical complications (OR?=?18.0; 95% CI 6.0‐54.1, p ?0.0001). A great diversity of mutations in MTTP has been observed (n?=?76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity. Conclusion The first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.