Rare Cholesterol Related Disorders: A Sterolomic Library for Diagnosis and Monitoring of Diseases

Abstract

Cholesterol is an essential molecule in all animals, it can be made by de novo synthesis and can be taken up from the diet. Inherited disorders of cholesterol synthesis, metabolism and transport lead to disease, often with neurological signs. However, such disorders tend to have non-specific symptoms and can be difficult to diagnose. In addition, there is no single diagnostic test applicable to multiple disorders of cholesterol synthesis, metabolism and transport which can be used to suggest or confirm a diagnosis, resulting in a delay in treatment, particularly in the case of unknown genetic variants. Here, we present the first version of a mass spectrometry sterolomic library to aid the diagnosis of manifold cholesterol-related inherited disorders of metabolism. The library was generated using technology based on simple derivatisation chemistry exploiting the Girard P hydrazine reagent and utilising electrospray ionisation mass spectrometry in the positive and negative modes. The library includes data for 13 autosomal recessive disorders and predicted data for a further 8 disorders.