First degree relatives of those with primary haemochromatosis should be screened to determine if they are a carrier or if they could develop the disease. This can allow preventive measures to be taken.

Screening the general population is not recommended.

There exist other causes of excess iron accumulation, which have to be considered before haemochromatosis is diagnosed.

- African iron overload, formerly known as Bantu siderosis, was first observed among people of African descent in Southern Africa. Originally, this was blamed on ungalvanised barrels used to store home-made beer, which led to increased oxidation and increased iron levels in the beer. Further investigation has shown that only some people drinking this sort of beer get an iron overload syndrome, and that a similar syndrome occurred in people of African descent who have had no contact with this kind of beer ("e.g.," African Americans). This led investigators to the discovery of a gene polymorphism in the gene for ferroportin which predisposes some people of African descent to iron overload.

- Transfusion haemosiderosis is the accumulation of iron, mainly in the liver, in patients who receive frequent blood transfusions (such as those with thalassaemia).

- Dyserythropoeisis, also known as myelodysplastic syndrome, is a disorder in the production of red blood cells. This leads to increased iron recycling from the bone marrow and accumulation in the liver.

There are several methods available for diagnosing and monitoring iron loading including:

- Serum ferritin: In males and postmenopausal females, a serum ferritin value of over 300 ng/mL (670 pmol/L) indicates iron overload. In premenopausal females, a serum ferritin value of over 150 or 200 ng/mL (330 or 440 pmol/L) indicates iron overload.

- Liver biopsy

- HFE

- MRI

Serum ferritin testing is a low-cost, readily available, and minimally invasive method for assessing body iron stores. However, the major problem with using it as an indicator of iron overload is that it can be elevated in a range of other medical conditions unrelated to iron levels including infection, inflammation, fever, liver disease, kidney disease, and cancer. Also, total iron binding capacity may be low, but can also be normal.

The standard of practice in diagnosis of haemochromatosis was recently reviewed by Pietrangelo. Positive HFE analysis confirms the clinical diagnosis of haemochromatosis in asymptomatic individuals with blood tests showing increased iron stores, or for predictive testing of individuals with a family history of haemochromatosis. The alleles evaluated by HFE gene analysis are evident in ~80% of patients with haemochromatosis; a negative report for HFE gene does not rule out haemochromatosis. In a patient with negative HFE gene testing, elevated iron status for no other obvious reason, and family history of liver disease, additional evaluation of liver iron concentration is indicated. In this case, diagnosis of haemochromatosis is based on biochemical analysis and histologic examination of a liver biopsy. Assessment of the hepatic iron index (HII) is considered the "gold standard" for diagnosis of haemochromatosis.

Magnetic resonance imaging (MRI) is emerging as a noninvasive alternative to accurately estimate iron deposition levels in the liver as well as heart, joints, and pituitary gland.

MRI-based testing is a non-invasive and accurate alternative to measure liver iron concentrations.

1) Detection of orotic acid in urine

2) Deficiency of Enzymes orotate phosphoribosyl transferase and OMP decarboxylase

Chronic liver disease takes several years to develop and the condition may not be recognised unless there is clinical awareness of subtle signs and investigation of abnormal liver function tests.

Testing for chronic liver disease involves blood tests, imaging including ultrasound and a biopsy of the liver. The liver biopsy is a simple procedure done with a fine thin needle under local anaesthesia. The tissue sample is sent to a laboratory where it is examined underneath a microscope.

Effective treatment of the disease has been confined to liver transplants. Success has also been reported with an antioxidant chelation cocktail, though its effectiveness cannot be confirmed. Based on the alloimmune cause hypothesis, a new treatment involving high-dose immunoglobulin to pregnant mothers who have had a previous pregnancy with a confirmed neonatal hemochromatosis outcome, has provided very encouraging results.

The condition is sometimes confused with juvenile hemochromatosis, which is a hereditary hemochromatosis caused by mutations of a gene called hemojuvelin. While the symptoms and outcomes for these two diseases are similar, the causes appear to be different.

No treatment is indicated for essential fructosuria, while the degree of fructosuria depends on the dietary fructose intake, it does not have any clinical manifestations. The amount of fructose routinely lost in urine is quite small. Other errors in fructose metabolism have greater clinical significance. Hereditary fructose intolerance, or the presence of fructose in the blood (fructosemia), is caused by a deficiency of aldolase B, the second enzyme involved in the metabolism of fructose. This enzyme deficiency results in an accumulation of fructose-1-phosphate, which inhibits the production of glucose and results in diminished regeneration of adenosine triphosphate. Clinically, patients with hereditary fructose intolerance are much more severely affected than those with essential fructosuria, with elevated uric acid, growth abnormalities and can result in coma if untreated.

Administration of cytidine monophosphate and uridine monophosphate reduces urinary orotic acid and ameliorates the anemia.

Administration of uridine, which is converted to UMP, will bypass the metabolic block and provide the body with a source of pyrimidine.

Uridine triacetate is a drug approved by FDA to be used in the treatment of hereditary orotic aciduria.

In a peripheral blood smear, the red blood cells will "appear" abnormally small and lack the central pale area that is present in normal red blood cells. These changes are also seen in non-hereditary spherocytosis, but they are typically more pronounced in hereditary spherocytosis. The number of immature red blood cells (reticulocyte count) will be elevated. An increase in the mean corpuscular hemoglobin concentration is also consistent with hereditary spherocytosis.

Other protein deficiencies cause hereditary elliptocytosis, pyropoikilocytosis or stomatocytosis.

In longstanding cases and in patients who have taken iron supplementation or received numerous blood transfusions, iron overload may be a significant problem. This is a potential cause of heart muscle damage and liver disease. Measuring iron stores is therefore considered part of the diagnostic approach to hereditary spherocytosis.

An osmotic fragility test can aid in the diagnosis. In this test, the spherocytes will rupture in liquid solutions less concentrated than the inside of the red blood cell. This is due to increased permeability of the spherocyte membrane to salt and water, which enters the concentrated inner environment of the RBC and leads to its rupture. Although the osmotic fragility test is widely considered the gold standard for diagnosing hereditary spherocytosis, it misses as many as 25% of cases. Flow cytometric analysis of eosin-5′-maleimide-labeled intact red blood cells and the acidified glycerol lysis test are two additional options to aid diagnosis.

A diagnosis of essential fructosuria is typically made after a positive test for reducing substances in the urine. The excretion of fructose in the urine is not constant, it depends largely on dietary intake.

Experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy.

Genetic testing for the presence of mutations in protein molecules is considered to be a confirmatory testing technique. It is important to know the risks regarding the transmission and dangers of HPP.

The treatment of chronic liver disease depends on the cause. Specific conditions may be treated with medications including corticosteroids, interferon, antivirals, bile acids or other drugs. Supportive therapy for complications of cirrhosis include diuretics, albumin, vitamin K, blood products, antibiotics and nutritional therapy. Other patients may require surgery or a transplant. Transplant is required when the liver fails and there is no other alternative.

Those with hereditary elliptocytosis have a good prognosis, only those with very severe disease have a shortened life expectancy.

At present there is no specific treatment. Many patients with haemolytic anaemia take folic acid (vitamin B) since the greater turnover of cells consumes this vitamin. During crises transfusion may be required. Clotting problems can occur for which anticoagulation may be needed. Unlike hereditary spherocytosis, splenectomy is contraindicated.

The diagnosis of hereditary elliptocytosis is usually made by coupling a family history of the condition with an appropriate clinical presentation and confirmation on a blood smear. In general it requires that at least 25% of erythrocytes in the specimen are abnormally elliptical in shape, though the observed percentage of elliptocytes can be 100%. This is in contrast to the rest of the population, in which it is common for up to 15% of erythrocytes to be elliptical.

If some doubt remains regarding the diagnosis, definitive diagnosis can involve osmotic fragility testing, an autohaemolysis test, and direct protein assaying by gel electrophoresis.

The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called bilirubin gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis.

The condition is usually asymptomatic, and is only noticed when screening for other hemoglobin disorders.

Hereditary persistence of fetal hemoglobin (HPFH, BrE: "Hereditary persistence of foetal haemoglobin") is a benign condition in which significant fetal hemoglobin (hemoglobin F) production continues well into adulthood, disregarding the normal shutoff point after which only adult-type hemoglobin should be produced.

Congenital hemolytic anemia (or hereditary hemolytic anemia) refers to hemolytic anemia which is primarily due to congenital disorders.

Treatment consists of frequent blood transfusions and chelation therapy. Potential cures include bone marrow transplantation and gene therapy.

Diagnosis of acquired dysfibrinogenemia uses the same laboratory tests that are used for congenital dysfibrinogenemia plus evidence for an underlying causative disease.

Basically classified by causative mechanism, types of congenital hemolytic anemia include:

- Genetic conditions of RBC Membrane

- Hereditary spherocytosis

- Hereditary elliptocytosis

- Genetic conditions of RBC metabolism (enzyme defects). This group is sometimes called "congenital nonspherocytic (hemolytic) anemia", which is a term for a congenital hemolytic anemia without spherocytosis, and usually excluding hemoglobin abnormalities as well, but rather encompassing defects of glycolysis in the erythrocyte.

- Glucose-6-phosphate dehydrogenase deficiency (G6PD or favism)

- Pyruvate kinase deficiency

- Aldolase A deficiency

- Hemoglobinopathies/genetic conditions of hemoglobin

- Sickle cell anemia

- Congenital dyserythropoietic anemia

- Thalassemia