Liver and the defects of cholesterol and bile acids biosynthesis: Rare disorders many diagnostic pitfalls

Abstract

In recent decades, biotechnology produced a growth of knowledge on the causes and mechanisms of metabolic diseases that have formed the basis for their study, diagnosis and treatment. Unfortunately, it is well known that the clinical features of metabolic diseases can manifest themselves with very different characteristics and escape early detection. Also, it is well known that the prognosis of many metabolic diseases is excellent if diagnosed and treated early. In this editorial we briefly summarized two groups of inherited metabolic diseases, the defects of cholesterol biosynthesis and those of bile acids. Both groups show variable clinical manifestations but some clinical signs and symptoms are common in both the defects of cholesterol and bile acids. The differential diagnosis can be made analyzing sterol profiles in blood and/or bile acids in blood and urine by chromatographic techniques (GC-MS and LC-MS/MS). Several defects of both biosynthetic pathways are treatable so early diagnosis is crucial. Unfortunately their diagnosis is made too late, due either to the clinical heterogeneity of the syndromes (severe, mild and very mild) that to the scarcity of scientific dissemination of these rare diseases. Therefore, the delay in diagnosis leads the patient to the medical observation when the disease has produced irreversible damages to the body. Here, we highlighted simple clinical and laboratory descriptions that can potentially make you to suspect a defect in cholesterol biosynthesis and/or bile acids, as well, we suggest appropriate request of the laboratory tests that along with common clinical features can help to diagnose these defects.

Keywords: Cholesterol; Bile acids; Liver metabolism; Gas chromatography coupled to mass spectrometry; Liquid chromatography coupled to tandem mass spectrometry

Core tip: The genetic defects of cholesterol and bile acid biosynthesis are characterized by a diversity of clinical findings affecting the liver, the intestine, and the nervous system. Many of these defects are efficaciously treatable but owing to mild phenotypes many cases can escape to an earlier diagnosis and are identified after few years or adulthood with irreversible injuries or more difficult to treat. Here, we highlighted simple clinical and laboratory descriptions that can potentially make you to suspect a defect in cholesterol biosynthesis and/or bile acids, in order to reduce the diagnostic delay and to improve the prognosis of these defects.