The enlarged spleen may put pressure on the stomach causing a loss of appetite and resulting weight loss. It may also present with mild fever and night sweats due to an elevated basal level of metabolism.Some (<10%) are diagnosed during the accelerated stage which most often presents bleeding, petechiae and ecchymosis. In these patients fevers are most commonly the result of opportunistic infections.Some patients are initially diagnosed in the blast phase in which the symptoms are most likely fever, bone pain and an increase in bone marrow fibrosis. Cause
In most cases, no obvious cause for CML can be isolated. Risk factors
CML is more common in males than in females (male to female ratio of 1.4:1) and appears more commonly in the elderly with a median age at diagnosis of 65 years. Exposure to ionising radiation appears to be a risk factor, based on a 50 fold higher incidence of CML in Hiroshima and Nagasaki nuclear bombing survivors. The rate of CML in these individuals seems to peak about 10 years after the exposure. Pathophysiology
CML was the first cancer to be linked to a clear genetic abnormality, the chromosomal translocation known as the Philadelphia chromosome. This chromosomal abnormality is so named because it was first discovered and described in 1960 by two scientists from Philadelphia, Pennsylvania, USA: Peter Nowell of the University of Pennsylvania and David Hungerford of Fox Chase Cancer Center.In this translocation, parts of two chromosomes (the 9th and 22nd) switch places.
Type 2A is caused by inheriting two mutated alleles, one from each parent, for the HJV (aka HFE2) gene, which encodes the protein hemojuvelin. Hemojuvelin is responsible for the maintaining correct levels of the protein hepcidin, which regulates iron absorption in the blood. Without functional hemojuvelin, hepcidin levels are reduced, and the amount of iron absorbed into the blood during digestion is unable to be halted. Type 2B is caused by inheriting two mutated alleles, one from each parent, for the HAMP gene, which encodes the protein hepcidin. Hepcidin is responsible for regulating absorption of iron from the small intestine to the blood during the digestion of food, such to prevent blood iron levels from becoming too high. A lack of functional hepcidin prevents the body from stopping iron absorption when it has already reached adequate levels.Type 2A is the most common form, accounting for roughly 9 out of every 10 cases of the disease. Diagnosis
An individual may be suspected to have this condition based on their medical history, physical exam findings, and blood tests, and confirmation of the diagnosis can be made with further testing, often with use of gene panels. Differential Diagnosis
Juvenile hemochromatosis shares signs and symptoms with many other conditions including:
Other types of hereditary hemochromatosis
Atransferrinemia
Aceruloplasminemia
African iron overload
Neonatal hemochromatosis
Transfusional iron overload and other forms of secondary hemochromatosis
Porphyria cutanea tarda

Blood Testing
The presence of hemochromatosis may be discovered incidentally on blood testing, or a diagnosis suspected based on symptoms may be supported or ruled out by blood testing.