Symptoms of classic HHC type IA
How does the typical patient with classic HHC type IA present?
Several factors, most notably physiologic blood loss in women and higher iron intake in men, modify the expression of classic HHC. Accordingly, the symptomatic stage is approximately 10 times more common in men than women, and men tend to have the onset of symptoms at an earlier age. Clinical manifestations usually appear between the ages of 40 and 60 years, but the disease severity is quite variable. A few patients may develop full clinical expression as early as age 20 years (rule out type II HHC), whereas 30% of HFE mutation homozygotes never develop clinical symptoms. The frequency and severity of clinical manifestations are becoming less with the earlier recognition of hemochromatosis.
HHC typically presents with asymptomatic abnormal liver function tests, with 95% of patients having hepatomegaly. Liver disease usually progresses to hepatic cirrhosis in untreated cases. Comorbid factors that increase hepatic steatosis include obesity, diabetes, and excess alcohol consumption. Hepatocellular carcinoma risk is increased by a factor of 20 to 200. A characteristic arthropathy occurs in 40% to 80% of patients and may be the initial manifestation, although more often it occurs later in the disease and may even develop after treatment has been initiated. Up to 33% can have lumbar spine degenerative disc disease and 25% to 35% can have osteoporosis due to hypogonadotrophic hypogonadism. Other manifestations include slate-gray skin caused by iron in eccrine sweat glands and brown skin pigmentation due to melanin deposition (50%), diabetes mellitus, and hypogonadism manifest as decreased libido (20%–40%), impotence, amenorrhea, or sparse body hair. Constitutional symptoms (80%) such as weakness or lethargy are also common. Cardiac involvement, manifested most commonly as congestive heart failure, is present in approximately 30% of patients and is a principal cause of death in untreated patients. Increased susceptibility to infections, particularly due to Vibrio vulnificus from uncooked seafood, is observed because of enhanced bacterial virulence and impaired macrophage clearance caused by high serum iron. Other infections observed at higher incidence in patients with iron overload include Yersinia enterocolitica , which causes a septic arthritis, Listeria monocytogenes , Salmonella typhimurium , and Mucor , among others.
