Hemochromatosis

Hemochromatosis

OVERVIEW:

A hereditary disorder in which the small intestine absorbs excessive iron. Since the body lacks any way to excrete iron, the excess is stored in glands and muscle, such as the liver, pancreas, and heart. Over the years, the involved organs begin to fail.

System(s) affected: Endocrine/Metabolic
Genetics: Autosomal recessive; acquired; mutation in HFE gene; associated with HLA-A3, HLA-B14, HLA-B7
Incidence/Prevalence in USA:
3 cases/1000 people (heterozygote frequency 1 in 10) - the most common abnormal gene in the US population
Predominant age: Present from birth, but symptoms usually present in the fifth and sixth decades
Predominant sex: Male = Female (clinical signs are more frequent in men (8:1 male to female ratio)

SIGNS AND SYMPTOMS:

• Weakness (83%)
• Abdominal pain (58%)
• Arthralgia (43%)
• Loss of libido or potency (38%)
• Amenorrhea (22%)
• Dyspnea on exertion (15%)
• Neurologic symptoms (6%)
• Hepatomegaly (83%)
• Increased skin pigmentation (75%)
• Loss of body hair (20%)
• Splenomegaly (13%)
• Peripheral edema (12%)
• Jaundice (10%)
• Gynecomastia (8%)
• Ascites (6%)
• Testicular atrophy
• Hepatic tenderness
• Diabetes mellitus symptoms

CAUSES:

• The mechanism for increased iron absorption in the face of excessive iron stores is unknown. Iron metabolism appears normal in this disease except for a higher level of circulating iron.
• Iron overload may be due to thalassemia, sideroblastic anemia, liver disease, excess iron intake, chronic transfusion

RISK FACTORS:

• The disease is a genetic disorder. Some variables influence the age of onset and severity of symptoms.
• Intake of iron, especially from vitamin supplements. These may contain large amounts of iron as well as vitamin C, which enhances iron absorption.
• Alcohol increases the absorption of iron (as high as 41% of patients with symptomatic disease are alcoholic)
• Loss of blood delays the onset of symptoms, such as blood loss in women because of menstruation and pregnancy.

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS:

• Repeated transfusions
• Hereditary anemias with ineffective erythropoiesis
• Alcoholic cirrhosis
• Porphyria cutanea tarda
• Atransferrinemia
• Excessive ingestion of iron (rare)

LABORATORY:

• Transferrin saturation (serum iron concentration divided by total iron-binding capacity x 100): greater than 70% is virtually diagnostic of iron overload; 45% or higher warrants further evaluation
• Serum ferritin: greater than 300 µg/L for men and post-menopausal women and 200 µg/L for pre-menopausal women
• Urinary iron
• Increased urine hemosiderin
• Hyperglycemia
• Decreased FSH
• Decreased LH
• Decreased testosterone
• Increased SGOT
• Hypoalbuminemia

Drugs that may alter lab results: Iron supplements, transfusions may elevate serum iron
Disorders that may alter lab results:
Inflammatory reactions, other forms of liver disease, certain tumors (e.g., acute granulocytic leukemia), rheumatoid arthritis may elevate serum ferritin

PATHOLOGICAL FINDINGS:

• Increased hepatic parenchymal iron stores
• Hepatic fibrosis and cirrhosis with hepatomegaly
• Pancreatic enlargement
• Excess hemosiderin in liver, pancreas, myocardium, thyroid, parathyroid, joints, skin
• Cardiomegaly
• Joint deposition of iron

SPECIAL TESTS:

After diagnosis established, consider oral glucose tolerance test to rule out diabetes and echocardiogram to rule out cardiomyopathy

IMAGING:

CT scan, MRI, and magnetic susceptibility measurement (MSM) are being studied for measuring body iron, but have not yet reached validation and general availability

DIAGNOSTIC PROCEDURES:

• Liver biopsy for stainable iron is the standard for diagnosis. Presence or absence of cirrhosis can also be ascertained.
• DNA PCR testing for HFE gene mutations C282Y and H63D - present in 85-90% of patients

TREATMENT

APPROPRIATE HEALTH CARE:

Outpatient

GENERAL MEASURES:

• Removal of excess iron by repeated phlebotomy once or twice weekly to establish and maintain a mild anemia (hematocrit of 37-39%)
• When the patient finally becomes iron deficient, a lifelong maintenance program of 4-6 phlebotomies a year to keep storage iron normal - maintain serum ferritin 50 µg/L

SURGICAL MEASURES:

N/A

ACTIVITY:

Full activity unless significant heart disease

DIET:

• An iron-poor diet is not of significant benefit
• Avoid alcohol, iron-fortified foods, iron-containing supplements, and uncooked shellfish
• Restrict vitamin C to small doses between meals
• Tea chelates iron and may be drunk with meals

PATIENT EDUCATION:

• Iron Overload Diseases Association, Inc., 433 Westwind Dr., North Palm Beach, FL 33408
• American Hemochromatosis Society, Inc., 777 East Atlantic Ave, Z-363, Delray Beach, FL 33483-5352

MEDICATIONS

DRUG(S) OF CHOICE:

None. Only when phlebotomy is not feasible or in the presence of severe heart disease should the iron-chelating agent deferoxamine (Desferal) be considered.

Contraindications: N/A
Precautions: N/A
Significant possible interactions: N/A

ALTERNATIVE DRUGS:

None

FOLLOW UP

PATIENT MONITORING:

• Measure hematocrit before each phlebotomy - skip phlebotomy if hematocrit is less than 36%
• Schedule an additional phlebotomy when hematocrit is greater than 40%
• When anemia becomes refractory, repeat transferrin saturation and serum ferritin to confirm depletion of iron stores
• When iron stores are depleted, 4 to 6 phlebotomies a year should keep iron stores normal
• During maintenance therapy, measure transferrin saturation and serum ferritin yearly
• Liver biopsy to assess iron stores when serum iron transferrin and ferritin results have not normalized

PREVENTION/AVOIDANCE:

Family members should be screened

POSSIBLE COMPLICATIONS:

• Cirrhosis
• Hepatoma (only in patients with cirrhosis)
• Diabetes mellitus
• Cardiomyopathy
• Arthritis
• Hypogonadism

EXPECTED COURSE AND PROGNOSIS:

• Patients diagnosed before cirrhosis develops and treated with phlebotomy have a normal life expectancy
• Life expectancy is reduced in patients with cirrhosis, diabetes mellitus, and patients that require longer than 18 months of phlebotomy therapy to return iron stores to normal

MISCELLANEOUS

ASSOCIATED CONDITIONS:

See Possible complications

AGE-RELATED FACTORS:

Pediatric: Although rare, iron overload can occur even as early as 2 years of age. The disorder can be diagnosed before iron overload is clinically apparent
Geriatric: N/A
Others: N/A

PREGNANCY:

Avoid iron supplements

SYNONYMS:

• Bronze diabetes
• Troisier-Hanot-Chauffard syndrome

ICD-9-CM:

275.0 Disorders of iron metabolism

(see images)

Want to discuss this term? Visit our forum or our chat room.

SEE ALSO (Enter the keywords below into our search box or click on the link):

n/a

Medical Diagnosis » H » Hemochromatosis