Inherited Disorders

Familial hypercholesterolaemia (FH) is characterised by very high levels of LDL cholesterol, leading to an increased risk of coronary heart disease (CHD) at an early age. Early and aggressive treatment with high doses of potent statins or statin combination therapy to lower LDL cholesterol significantly reduces CHD morbidity and mortality for people with FH.

Almost all patients affected by coeliac disease have specific variants of the human leucocyte antigens DQ2 and DQ8.These variants have a strong negative predictive value for diagnosis.

Factor V and Prothrombin are proteins involved in coagulation. A common variant in the Factor V gene and a common variant in the Prothrombin gene have both been implicated in an increased risk of thrombosis.

Hereditary haemochromatosis is a common inherited disorder in which excessive iron is absorbed. Genetic predisposition leads to disease in some but not all cases.

The MTHFR gene produces the enzyme methylenetetrahydrofolate reductase (MTHFR). Studies have reported associations of MTHFR polymorphisms with many conditions including autism, schizophrenia, coronary artery disease, foetal neural tube defects, poor pregnancy outcomes and colorectal cancer.

HLA-B27 is an MHC class I molecule that is associated with a variety of inflammatory conditions.

The ApoE gene codes for the protein apoliprotein E. This protein has been implicated in a range of disorders related to lipid metabolism.

Alpha-thalassaemia is a recessive haematological disorder characterised by defects in the production of alpha globin chain of the haemoglobin molecule that decrease normal haemoglobin production with resulting microcytic hypochromic anaemia. The disease typically results from deletions involving the HBA1 and HBA2 genes, though other less frequent mutations can also cause the disorder.

Beta Thalassemia is a recessive haematological disorder caused by defects in the production of the beta globin chain of the haemoglobin molecule, caused by mutations in the HBB gene. The severity of the disease depends on variations involved and their presence on one (heterozygous) or both (homozygous) alleles. Other laboratory finding can include microcytic, hypochromic anaemia, and a raised HbA2 on haemoglobin electrophoresis.

Caused by inherited mutations in the FMR1 gene, Fragile X syndrome is the most common cause of familial intellectual disability. This is an X-linked disorder with a complex clinical phenotype.

Caused by inherited variations in the CFTR gene, depending on their number and type, a variety of clinical outcomes can be observed. These vary from being unaffected to severe lung and pancreatic disorders (CF) or milder effects such as male infertility, bronchiectasis or pancreatitis. This test is included in the Genetic Carrier Screen panel.

Gilbert’s syndrome is characterised by jaundice due to increased levels of unconjugated plasma bilirubin. Men are at higher risk than females and usually present post-puberty. In people of northern European ancestry, cases of Gilbert’s syndrome are often associated with inheriting two copies (one from each parent) of a specific mutation in the promoter region of the gene encoding the enzyme glucuronyltransferase (UGT1A1), designated UGT1A1*28 allele. UGT1A1 is a liver enzyme important for clearing conjugated bilirubin from the circulation. In general, other than the low grade elevated bilirubin levels, people with Gilbert’s syndrome exhibit no other signs or symptoms.

Testing for Gilbert’s syndrome may assist in differentiating the cause of isolated elevated bilirubin levels in those patients with normal test results for FBC, reticulocytes, haptoglobin and liver enzymes.