Hereditary Hemochromatosis
WHAT IS HEREDITARY HEMOCHROMATOSIS?
Hereditary Hemochromatosis (HH) is the most common genetic disorder
known. It occurs in about 1 in 200 to 1 in 400 Caucasians, and approximately 12%
(1 in 8) of Caucasians carry the gene for HH. HH occurs less frequently in other
ethnic groups.
WHAT ARE THE MOST COMMON FEATURES OF HH?
HH is characterized by excess iron absorption from the gastrointestinal tract
leading to storage of iron in the organs and eventually multiple organ damage,
if left untreated. Symptoms of HH usually appear in adulthood (40-60 years), but
there are documented cases of HH in children and young adults. Early symptoms of
HH are often non-specific and include malaise, fatigue, impotence, abdominal
pain, and joint pain. In the absence of treatment, serious complications include
chronic liver disease and cirrhosis, hepatic carcinoma (liver cancer), diabetes
(also referred to as bronze diabetes) and heart disease. Arthritis may develop
and there may be a gradual darkening of the skin from a grayish hue to the
characteristic bronze color known to be associated with HH. All of the above
complications of HH can be prevented by early detection and treatment with
phlebotomy (routine removal of blood via venipuncture). Because women lose blood
during menstruation and pregnancy, symptoms occur less often or at later ages in
women than in men.
HOW IS HH INHERITED?
HH is an autosomal recessive disorder. Autosomal means the abnormal gene is
not on a sex chromosome. Recessive means the effect of the gene would only be
seen when a person inherits an abnormal recessive gene from both parents. People
who are carriers of HH have one abnormal (mutated) copy of the gene and one
normal copy of the gene. When both parents are carriers of HH, they have a 25%
risk (1 in 4 chances) of having a child who may develop HH, a 50% risk (1 in 2
chances) of having an unaffected carrier child, and a 25% chance of having an
unaffected, non-carrier child with each pregnancy.
HOW IS THE HH TEST PERFORMED?
A DNA blood test can identify changes (mutations) within the HH gene. DNA
studies detect individuals with the most common HH mutation, Cys282Tyr (C282Y),
and a second mutation implicated in HH, known as His63Asp (H63D). Approximately
85-93% of people with HH have two copies of the Cys282Tyr mutation (homozygous
for Cys282Tyr). Most homozygotes of the Cys282Tyr mutation develop
hemochromatosis, and some heterozygotes (carrying one copy of the Cys282Tyr
mutation) may have mild symptoms of HH such as lethargy, joint pain, and
weakness. Another 3-5% of affected individuals are considered compound
heterozygotes and have one Cys282Tyr mutation and one His63Asp mutation. Of
people identified to be compound heterozygotes, only 1.5% in the general
population develop clinical hemochromatosis.
WHO SHOULD HAVE HH TESTING?
HOW LONG DOES IT TAKE TO COMPLETE THE TEST?
The DNA test for Hemochromatosis is completed within 2-4 days.
HOW CAN HH TESTING BE ARRANGED?
Physicians or healthcare providers may contact one of our Centers for
consultations. Blood specimens may be sent by a physician or drawn at GeneCare
if testing is recommended.
Individuals who are concerned about the risk of carrying the HH gene are encouraged to discuss genetic testing with their physicians or healthcare providers and to consider having genetic counseling at GeneCare. During counseling, a detailed family history will be reviewed and appropriate testing determined for each individual situation.
SPECIMEN COLLECTION:
SPECIMEN TRANSPORT:
GeneCare Medical Genetics Center, 120 Conner Drive, Suite
201, Chapel Hill, NC 27514-7085
(919) 942-0021 • 1-800-277-4363 • Fax (919) 967-9519
Or
GeneCare Medical Genetics Center, Wilson Genetics Laboratory,
4701 Randolph Rd, Suite G9, Rockville, MD 208525
(301) 881-2592 • 1-866-881-2592 • Fax (301) 881-2596
REFERENCES
Adams, PC. Hemochromatosis: new insights in pathogenesis and diagnosis
following the discovery of the gene. Crit. Rev Clin Lab Sciences 1998;
35(3): 239-273.
Bacon, B. et al. Molecular medicine and hemochromatosis: at the crossroads. Gastroenterology 1999; 116(1): 193-207.
Beutler, E. The significance of the 187G (H63D) mutation in hemochromatosis. Am J Hum Genet 1997; 61: 762-764.
Witte, DL et al. Practice Guidelines Development Task Force of the College of American Pathologists: Hereditary Hemochromatosis. Clinica Chimica Acta 1996; 245: 139-200.
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