Case Report: Next Generation Sequencing in Clinical Practice–A Real Tool for Ending the Protracted Diagnostic Odyssey

Abstract

We reported a case of sitosterolemia, which is a rare genetic disease, characterized by increased plant sterol absorption and great heterogeneity of clinical manifestations. Our patient was initially referred to the lipid clinic due to high cholesterol levels and premature cardiovascular disease. Diagnosis of familial hypercholesterolemia was established in accordance with the Dutch Lipid Clinic Network criteria. Next-generation sequencing was later performed, which revealed a nonsense mutation in the ABCG8 gene, which led to the diagnosis of sitosterolemia. The aim of our report is to demonstrate, how genetic testing helped to make the correct diagnosis and to explain many of the patient's health problems, which etiology remained unclear for many years.

Pediatric Patients with Sitosterolemia: Next-Generation Sequencing and Biochemical Examination in Clinical Practice

“…We can assume that nonsense variants are associated with higher phytosterol levels, as was found in case 2, where the proband had the p.(Trp361*) variant and a sitosterol concentration of 69.6 µmol/L. The sitosterol concentration was as high as 54.4 µmol/L in adult patients homozygous for p.(Trp361*), as was described earlier [5].…”

“…The major clinical manifestation of sitosterolemia as discussed today are xanthomas [1]. As some sitosterolemic patients have elevated cholesterol levels, misdiagnosis of sitosterolemia with familial hypercholesterolemia may be rather prevalent and lead to the treatment that could even worthen the disease progression [4,5]. However, patients with sitosterolemia may present with normal cholesterol levels as well how it was described in the first cases [6].…”

“…Sitosterolemia can also been presented with hematological abnormalities-anemia and thrombocytopenia. Eventually, years could pass until patients receive the proper diagnosis and treatment [5,7]. Thereafter, NGS with the custom panels including ABCG5 and ABCG8 and biochemical phytosterol evaluation are the approaches that allow for precise diagnosis.…”