Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (983 page)

   Limitations

   ELISA requires well-trained, experienced technologists for accurate performance.

   Serotonin release requires the use of radioactive materials. It is performed in only a few reference laboratories.

HEREDITARY HEMOCHROMATOSIS MUTATION ASSAY
*

   Definition

   Hereditary hemochromatosis (HH; OMIM# 235200) testing identifies mutations in the
HFE
gene.
HFE
mutations exhibit incomplete penetrance; therefore, the HFE genotype cannot be used as the sole diagnostic criterion for disease. The majority (approximately 80–90%) of HH patients are homozygous for the
C282Y
mutation. Less than 2% of all
C282Y
/
H63D
compound heterozygotes will develop HH. Other reported genotypes associated with a clinical diagnosis of HH include compound heterozygosity for
C282Y/S65C
and homozygosity for
H63D
.

   
Normal values:
negative or no mutations are found.

   Use

   Confirmatory diagnostic testing

   Predictive testing for at-risk relatives

   Carrier testing (for the identification of heterozygotes)

   Prenatal diagnosis (rarely performed)

   Two groups of tests are available:

   Targeted mutation panels test for only two:
p.C282Y
(
c.845G>A
) and
p.H63D
(
c.187C>G
), or three mutations including
p.S65C
(
c.193A>T)