Disorders of the metabolism of sterols gene panel

Disorders of the Metabolism of Sterols – Gene Panel

Test Overview
The Disorders of the Metabolism of Sterols Gene Panel is a comprehensive genetic test designed to identify pathogenic variants in genes involved in sterol biosynthesis, transport, metabolism, and regulation. It supports the diagnosis of inherited sterol metabolism disorders and helps establish the underlying molecular cause of unexplained developmental, neurological, hepatic, skeletal, or multisystem abnormalities.

Clinical Indications

The panel may be considered in individuals with:

• Suspected inherited sterol or cholesterol metabolism disorders
• Abnormal cholesterol or sterol profiles without an apparent acquired cause
• Developmental delay, intellectual disability, or neurological abnormalities
• Congenital anomalies or distinctive facial features
• Skeletal abnormalities or growth disturbances
• Liver dysfunction or unexplained hepatomegaly
• Disorders suggestive of impaired cholesterol biosynthesis
• Familial or unexplained dyslipidemia
• Prenatal or neonatal findings suggestive of a sterol synthesis disorder
• A family history of a known or suspected inherited sterol disorder

Disorders Covered

Depending on the panel design, analysis may help detect conditions such as:

• Smith-Lemli-Opitz syndrome
• Cerebrotendinous xanthomatosis
• Sitosterolemia
• Desmosterolosis
• Lathosterolosis
• Mevalonic aciduria and related mevalonate pathway disorders
• Lysosomal acid lipase-related disorders
• Other inherited disorders affecting cholesterol and sterol homeostasis

Genes Commonly Associated

The panel may include genes such as:

• DHCR7
• CYP27A1
• ABCG5
• ABCG8
• LBR
• SC5D
• EBP
• NSDHL
• HMGCR
• MVK
• PMVK
• MVD
• IDI1
• LIPA
• Other clinically relevant genes involved in sterol metabolism

The exact gene list varies according to the laboratory's validated panel.

Sample

Peripheral blood in an EDTA tube is commonly used. Other specimen types may be accepted according to laboratory protocol.

Method

Testing may involve next-generation sequencing (NGS) with variant analysis. Depending on the laboratory's validated methodology, copy-number variant (CNV) analysis and other variant detection approaches may also be included.

Clinical Utility

A molecular diagnosis can help:

• Confirm or refine a suspected diagnosis
• Guide appropriate clinical management
• Support targeted biochemical investigations
• Enable family testing and genetic counselling
• Assist with recurrence-risk assessment
• Facilitate appropriate long-term monitoring

Interpretation

Variants are classified according to established clinical variant-interpretation guidelines. Results should be interpreted alongside the patient's clinical presentation, biochemical findings, family history, and other laboratory investigations.

Note: A negative result does not completely exclude a genetic disorder, as some disease-causing variants or mechanisms may not be detectable by the test methodology.