History and exam

Key diagnostic factors

common

fatigue

Common but nonspecific symptom.

weakness

Common but nonspecific symptom.

lethargy

Common but nonspecific symptom.

arthralgias

Common presentations include calcium pyrophosphate crystal deposition, including pseudogout, and chronic arthropathy.[26][27]

Classic changes are akin to a noninflammatory osteoarthritis of the second and third metacarpophalangeal joints and proximal interphalangeal joints. Less frequently this can affect the wrist, knees, hips, and shoulders. Hand x-rays can show squared-off bone ends with hook-like osteophytes, joint space narrowing, sclerosis, chondrocalcinosis (radiographic calcification in hyaline and/or fibrocartilage), and cyst formation.

hepatomegaly

Present in 10% to 30% at diagnosis; usually associated with cirrhosis.[19]

diabetes mellitus

Present in up to 25% of patients at diagnosis; frequently accompanies cirrhosis.[20]

impotence in males

Hypogonadism is the second most common endocrine disorder associated with hemochromatosis, after diabetes.[37]

amenorrhea

Amenorrhea may be associated with hemochromatosis; testing for hemochromatosis in women with amenorrhea is recommended.[8]

loss of libido

Hypogonadism is the second most common endocrine disorder associated with hemochromatosis, after diabetes.[37]

skin pigmentation

May begin as a bronzing of the skin but then progress to gray or brown with slate-gray patches in the mouth.

Changes are usually generalized, but most frequently occur on the face, neck, extensor aspects of the lower forearms, dorsum of the hands, lower legs, genitals, and in old scars.[36]

Other diagnostic factors

uncommon

congestive heart failure

A chronic process from iron infiltration into the heart, but can present acutely with fluid overload or arrhythmias.[36]

arrhythmias

Atrial fibrillation or sick sinus syndrome result from iron-related conduction abnormalities.[36]

porphyria cutanea tarda

There is an increased prevalence of HFE mutations in patients with porphyria cutanea tarda, and increased iron levels can exacerbate symptoms from porphyria cutanea tarda.[39] Porphyria cutanea tarda is characterized by skin disease (fragile skin, blisters, bullae) and liver dysfunction (mild elevations in liver enzymes).

Risk factors

strong

middle age

In classic hemochromatosis, symptoms become clinically apparent in the fourth or fifth decade of life.

male sex

Men tend to present at a younger age than women, who are protected somewhat from iron overload by their natural iron losses associated with menses and childbirth.[12]

A large study of patients of northern European descent (ages 40-69 years) showed that among C282Y homozygotes, iron overload-related disease was seen in 28% of men and 1.2% of women.[13]​​​

white ancestry

The homozygous C282Y mutation is present in approximately 80% to 90% of patients of northern European origin who have typical hemochromatosis.[2][8]

family history

The classical form is an autosomal-recessive disorder. Screening is recommended for siblings and children of affected patients.[4][7][8]​​

supplemental iron

Diets with high iron intake have been linked to a higher incidence of clinical manifestations in patients with homozygous mutations.[22] Foods that are high in iron include red meat, leafy green vegetables, and liver.

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