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.

backgroundOur 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.

methodsWe 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.

resultsOur 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.

conclusionThe 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.