Disorders in sterol metabolism: A case series

Disorders of sterol metabolism are rare genetic conditions with phenotypic heterogeneity. Early diagnosis is crucial for precise management and genetic counselling. Patient 1 presented with intellectual disability, facial dysmorphism, limb anomalies, bilateral cataracts, elevated liver transaminases and severe liver fibrosis. Exome sequencing identified two likely pathogenic variants in exon 3 of the SC5D gene. Plasma lathosterol was 54 μmol/L (RR<10) confirming the diagnosis of lathosterolosis. Simvastatin treatment resulted in lowering of lathosterol, improvement in liver transaminases and fibrosis. Patient 2 had multiple xanthomas since 5.5 years of age. Initial diagnosis of juvenile xanthogranuloma was made based on histology and clinical presentation. Total cholesterol 12.8 mmol/L (RR 2.5–4.9) and LDL 10.3 mmol/L (RR <3.5) were noted at 8 years of age. Despite a low cholesterol diet and simvastatin up to 40 mg daily, there was minimal biochemical response. Exome sequencing identified two pathogenic variants in the ABCG8 gene. Plasma sitosterol was 736 mmol/L (RR <20) confirming the diagnosis of sitosterolaemia. A diet low in cholesterol and plant sterols and Ezetimibe at 10 mg resulted in reduction of xanthomas and improvement in lipid profile. These two patients highlight the importance of an accurate diagnosis, targeted treatment, the clinical benefits of a full sterol profile analysis and genomic sequencing.