Juvenile hemochromatosis (or hemochromatosis type 2) is, as its name indicates, a form of hemochromatosis which emerges during youth.

There are two forms:

- "HFE2A" is associated with hemojuvelin

- "HFE2B" is associated with hepcidin antimicrobial peptide

Some sources only specifically include hemojuvelin as a cause of juvenile hemochromatosis.

Haemochromatosis is in its manifestations, "i.e.", often presenting with signs or symptoms suggestive of other diagnoses that affect specific organ systems. Many of the signs and symptoms below are uncommon and most patients with the hereditary form of haemochromatosis do not show any overt signs of disease nor do they suffer premature morbidity.

The classic triad of cirrhosis, bronze skin and diabetes is not as common any more because of earlier diagnosis.

The more common clinical manifestations include:

- Fatigue

- Malaise

- Joint and bone pain

- Liver cirrhosis (with an increased risk of hepatocellular carcinoma) Liver disease is always preceded by evidence of liver dysfunction including elevated serum enzymes specific to the liver, clubbing of the fingers, leuconychia, asterixis, hepatomegaly, palmar erythema and spider naevi. Cirrhosis can also present with jaundice (yellowing of the skin) and ascites.

- Insulin resistance (often patients have already been diagnosed with diabetes mellitus type 2) due to pancreatic damage from iron deposition

- Erectile dysfunction and hypogonadism, resulting in decreased libido

- Congestive heart failure, abnormal heart rhythms or pericarditis

- Arthritis of the hands (especially the second and third MCP joints), but also the knee and shoulder joints

- Damage to the adrenal gland, leading to adrenal insufficiency

Less common findings including:

- Deafness

- Dyskinesias, including Parkinsonian symptoms

- Dysfunction of certain endocrine organs:

- Parathyroid gland (leading to hypocalcaemia)

- Pituitary gland

- More commonly a slate-grey or less commonly darkish colour to the skin (see pigmentation, hence its name "diabetes bronze" when it was first described by Armand Trousseau in 1865)

- An increased susceptibility to certain infectious diseases caused by siderophilic microorganisms:

- "Vibrio vulnificus" infections from eating seafood or wound infection

- "Listeria monocytogenes"

- "Yersinia enterocolica"

- "Salmonella enterica" (serotype Typhymurium)

- "Klebsiella pneumoniae"

- "Escherichia coli"

- "Rhizopus arrhizus"

- "Mucor" species

Males are usually diagnosed after their forties and fifties, and women several decades later, owing to regular iron loss through menstruation (which ceases in menopause). The severity of clinical disease in the hereditary form varies considerably. There is evidence suggesting that hereditary haemochromatosis patients affected with other liver ailments such as hepatitis or alcoholic liver disease suffer worse liver disease than those with either condition alone. There are also juvenile forms of hereditary haemochromatosis that present in childhood with the same consequences of iron overload.

Iron is stored in the liver, the pancreas and the heart. Long-term effects of haemochromatosis on these organs can be very serious, even fatal when untreated. For example, similar to alcoholism, haemochromatosis can cause cirrhosis of the liver. The liver is a primary storage area for iron and will naturally accumulate excess iron. Over time the liver is likely to be damaged by iron overload. Cirrhosis itself may lead to additional and more serious complications, including bleeding from dilated veins in the esophagus (esophageal varices) and stomach (gastric varices) and severe fluid retention in the abdomen (ascites). Toxins may accumulate in the blood and eventually affect mental functioning. This can lead to confusion or even coma (hepatic encephalopathy).

Liver cancer: Cirrhosis and haemochromatosis together will increase the risk of liver cancer. (Nearly one-third of people with haemochromatosis and cirrhosis eventually develop liver cancer.)

Diabetes: The pancreas which also stores iron is very important in the body’s mechanisms for sugar metabolism. Diabetes affects the way the body uses blood sugar (glucose). Diabetes is in turn the leading cause of new blindness in adults and may be involved in kidney failure and cardiovascular disease.

Congestive heart failure: If excess iron in the heart interferes with the its ability to circulate enough blood, a number of problems can occur, even death. The condition may be reversible when haemochromatosis is treated and excess iron stores reduced.

Heart arrhythmias: Arrhythmia or abnormal heart rhythms can cause heart palpitations, chest pain and light-headedness and are occasionally life-threatening. This condition can often be reversed with treatment for haemochromatosis.

Pigment changes: Bronze or grey coloration of the skin is caused primarily by increased melanin deposition, with iron deposition playing a lesser role.

Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is an autosomal recessive

metabolic disorder in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism of uracil and thymine.

Individuals with this condition may develop life-threatening toxicity following exposure to 5-fluorouracil (5-FU), a chemotherapy drug that is used in the treatment of cancer. Beside 5-FU, widely prescribed oral fluoropyrimidine capecitabine (Xeloda) could put DPD-deficient patients at risk of experiencing severe or lethal toxicities as well.

Symptoms can be extremely varied among those suffering from pyruvate kinase deficiency. The majority of those suffering from the disease are detected at birth while some only present symptoms during times of great physiological stress such as pregnancy, or with acute illnesses (viral disorders). Symptoms are limited to or most severe during childhood. Among the symptoms of pyruvate kinase deficiency are:

- Mild to severe hemolytic Anemia

- Cholecystolithiasis

- Tachycardia

- Hemochromatosis

- Icteric sclera

- Splenomegaly

- Leg ulcers

- Jaundice

- Fatigue

- Shortness of breath

Defined as those seen in any macrocytic, megaloblastic anemia:

- Anemia: causing fatigue, conjuctival pallor, pale complexion, and in some cases, a mild icterus (yellowing of the eye).

- Glossitis ("shiny tongue"): shiny, glossy tongue.

- Cheilosis (stomatitis): Inflammation of the edges of the lips and the oral mucosa.

- Tabes dorsalis ("subacute combined degeneration of the spinal cord"): This involves the posterior section of the spinal cord and therefore involves proprioception (sense of position), touch, sense of vibration and in severe cases the lateral corticospinal tract, causing spastic paralysis of the limbs.

- Peripheral neuropathy: tingling sensation in the arms and legs.

- Pancytopenia: decreased number of blood cells of all lineages (RBCs, leucocytes, platelets), due to decreased bone marrow production.

- Methylmalonyl CoA-emia: defined as blood having an unusually high concentration of methylmalonyl CoA.

- Peripheral findings such as hypersegmented neutrophils and large RBCs on high field view of the blood smears.

- Laboratory findings indicating increased MCV (Mean Corpuscular Volume), decreased Hgb/Hct (indicating anemia), and decreased value of vitamin B in the blood.

- Proteinuria: protein found in the urine detected by analysis or by dipstick.

- Reversal of all symptoms except neurological symptoms, by IV injection of vitamin B.

- Schilling test indicating no radioactive vitamin B in the urine. (This test has dropped out of favor and should not be tried in patients with any form of renal failure).

Organs commonly affected by haemochromatosis are the liver, heart, and endocrine glands.

Haemochromatosis may present with the following clinical syndromes:

- Cirrhosis of the liver: Varies from zonal iron deposition to fibrosis (cirrhosis).

- Diabetes due to selective iron deposition in pancreatic islet beta cells leading to functional failure and cell death.

- Cardiomyopathy

- Arthritis, from calcium pyrophosphate deposition in joints. The most commonly affected joints are those of the hands, particularly the knuckles of the second and third fingers.

- Testicular failure

- Bronzing of the skin. This deep tan color, in concert with insulin insufficiency due to pancreatic damage, is the source of a nickname for this condition: "bronze diabetes".

- Joint pain and bone pain

Porphyria cutanea tarda (commonly referred to as PCT) is recognized as the most prevalent subtype of porphyritic diseases.

The disease is characterized by onycholysis and blistering of the skin in areas that receive higher levels of exposure to sunlight. The primary cause of this disorder is a deficiency of uroporphyrinogen decarboxylase (UROD), a cytosolic enzyme that is a step in the enzymatic pathway that leads to the synthesis of heme. While a deficiency in this enzyme is the direct cause leading to this disorder, there are a number of both genetic and environmental risk factors that are associated with PCT.

Typically, patients who are ultimately diagnosed with PCT first seek treatment following the development of photosensitivities in the form of blisters and erosions on commonly exposed areas of the skin. This is usually observed in the face, hands, forearms, and lower legs. It heals slowly and with scarring. Though blisters are the most common skin manifestations of PCT, other skin manifestations like hyperpigmentation (as if they are getting a tan) and hypertrichosis (mainly on top of the cheeks) also occur. PCT is a chronic condition, with external symptoms often subsiding and recurring as a result of a number of factors. In addition to the symptomatic manifestation of the disease in the skin, chronic liver problems are extremely common in patients with the sporadic form of PCT. These include hepatic fibrosis (scarring of the liver), cirrhosis, and inflammation. However, liver problems are less common in patients with the inherited form of the disease. Additionally, patients will often void a wine-red color urine with an increased concentration of uroporphyrin I due to their enzymatic deficiency.

Tricho-hepato-enteric syndrome is one particular form of intractable diarrhea of infancy, presenting typically in the first month of life. These babies were usually born small for their age and continue to experience failure to thrive, usually with a final short stature. Typical facial features include prominent forehead and cheeks, a broad nasal root and widely spaced eyes (hypertelorism). Their hairs are woolly, easily removed and poorly pigmented. Liver disease is mainly present as cirrhosis or fibrosis, and staining might reveal high iron content of the liver cells (consistent with hemochromatosis). Most evaluated patients had some degree of decrease in intelligence.

Genes involved in iron metabolism disorders include HFE and TFR2.

Hepcidin is the master regulator of iron metabolism and, therefore, most genetic forms of iron overload can be thought of as relative hepcidin deficiency in one way or another. For instance, a severe form of iron overload, juvenile hemochromatosis, is a result of severe hepcidin deficiency. The majority of cases are caused by mutations in the hemojuvelin gene (HJV or RGMc/repulsive guidance molecule c). The exceptions, people who have mutations in the gene for ferroportin, prove the rule: these people have plenty of hepcidin, but their cells lack the proper response to it. So, in people with ferroportin proteins that transport iron out of cells without responding to hepcidin's signals to stop, they have a deficiency in the action of hepcidin, if not in hepcidin itself.

But the exact mechanisms of most of the various forms of adult hemochromatosis, which make up most of the genetic iron overload disorders, remain unsolved. So while researchers have been able to identify genetic mutations causing several adult variants of hemochromatosis, they now must turn their attention to the normal function of these mutated genes.

These genes represent multiple steps along the pathway of iron regulation, from the body's ability to sense iron, to the body's ability to regulate uptake and storage. Working out the functions of each gene in this pathway will be an important tool for finding new methods of treating genetic disorders, as well as for understanding the basic workings of the pathway.

So though many mysteries of iron metabolism remain, the discovery of hepcidin already allows a much better understanding of the nature of iron regulation, and makes researchers optimistic that many more breakthroughs in this field are soon to come.

Imerslund–Gräsbeck syndrome, is a rare autosomal recessive, familial form of vitamin B deficiency caused by malfunction of the ""Cubam"" receptor located in the terminal ileum. This receptor is composed of two proteins, amnionless (AMN), and cubilin. A defect in either of these protein components can cause this syndrome. This is a rare disease, with a prevalence about 1 in 200,000, and is usually seen in patients of European ancestry.

Vitamin B is an important vitamin needed for bone marrow functioning, the deficit of which causes decreased marrow output and anemia. Vitamin B has two forms, one of which, along with folate, is important in DNA synthesis. Vitamin B is sensitive to acid deformation in the stomach, so a molecule called haptocorrin (R-factor), protects it in the stomach. In the small bowel, a molecule named intrinsic factor (IF), allows vitamin B to be absorbed in the ileum. IGS is caused by a mutation in the receptors located in the terminal portion of ileum. This is a very rare, and unlikely cause of vitamin B deficiency but is a cause nonetheless.

Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.

Tricho-hepato-enteric syndrome (THE), also known as syndromic or phenotypic diarrhea, is an extremely rare congenital bowel disorder which manifests itself as intractable diarrhea in infants with intrauterine growth retardation, hair and facial abnormalities. Many also have liver disease and abnormalities of the immune system. The associated malabsorption leads to malnutrition and failure to thrive.

It is thought to be a genetic disorder with an autosomal recessive inheritance pattern, although responsible genes have not been found and the exact cause remains unknown. Prognosis is poor; many patients die before the age of 5 (mainly from infections or cirrhosis), although most patients nowadays survive with intravenous feeding (parenteral nutrition).

Porphyria cutanea tarda (PCT) is the most common subtype of porphyria. The disease is named because it is a porphyria that often presents with skin manifestations later in life. The disorder results from low levels of the enzyme responsible for the fifth step in heme production. Heme is a vital molecule for all of the body's organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood.

Hepatoerythropoietic porphyria has been described as a homozygous form of porphyria cutanea tarda, although it can also be caused if two different mutations occur at the same locus.

Iron overload, also known as haemochromatosis, indicates accumulation of iron in the body from any cause. The most important causes are hereditary haemochromatosis (HHC), a genetic disorder, and transfusional iron overload, which can result from repeated blood transfusions.

Neonatal Hemochromatosis is a rare and severe liver disease of unknown origin, though research suggests that it may be alloimmune condition. Its characteristics are similar to hereditary hemochromatosis, where iron deposition causes damage to the liver and other organs and tissues.

The only symptoms seen consistently in all 24 diagnosed cases are epilepsy, amelogenesis imperfecta in both primary and secondary teeth, and developmental delay. All symptoms experienced are experienced in varying degrees across each case.

There are some physical symptoms that have been associated with KTS. The most prominent symptom is amelogenesis imperfecta which gives the teeth a stained brown-yellow color. The enamel is thin, rough, and prone to crumbling. Two types of amelogenesis imperfecta (AI) have been seen in KTS patients. The first is Hypoplastic which is caused by the enamel being underdeveloped, and the second is hypo-calcified which causes the enamel to be soft and chalky. AI originated as a heterogeneous syndrome but has been observed as homogeneous in the case of KTS. Other physical symptoms that some cases have presented with include broad thumbs and toes, microcephaly, coarse hair, mildly asymmetric skull, up slanting palpebral fissures which is where the outside corners of the eyes are higher than normal, and smooth philtrum which is where the upper lip does not have a dip in the center.

KTS also presents itself with symptoms that affect the patient's ability to function. To varying degrees, patients either do not develop or have under developed language skills as well as under developed ambulance which is the ability to move around. Patients also present with global developmental delay. The severity of these symptoms is correlated with the intensity, frequency, and age of onset of the patient's epilepsy as well as their responsiveness to treatment for the epileptic attacks. In some severe cases, patients develop spastic tetraplegia which is the loss of function in all four limbs.

The extreme variability of symptoms was well represented in one family with 5 affected children. The first child was in a vegetative state and died at age 2. The second child showed psychomotor developmental delay at 1 month old, and epilepsy unresponsive to treatment at 9 months old. This child was also nonverbal and non ambulant. The third child's epilepsy was responsive to treatment and was ambulant, but she had an intellectual disability and only slight verbal abilities. The fourth child demonstrated developmental delay at age 6 months and had epileptic attacks that were only partially responsive to treatment. This child was non verbal and awkwardly ambulant. The fifth child was ambulant, but nonverbal and had epilepsy that was partially responsive to treatment. This variation has been seen across other cases of KTS as well.

The causes of neonatal hemochromatosis are still unknown, but recent research has led to the hypothesis that it is an alloimmune disease. Evidence supporting this hypothesis includes the high rate among siblings (>80%). This evidence along with other research indicates that neonatal hemochromatosis could be classified as a congenital alloimmune hepatitis.

Kohlschütter-Tönz syndrome (KTS), also called Amelo-cerebro-hypohidrotic syndrome is a rare inherited syndrome characterized by epilepsy, dementia, intellectual disability, and yellow teeth caused by amelogenesis imperfecta (abnormal formation of tooth enamel). It is a type A ectodermal dysplasia.

It is autosomal recessive and symptoms appear in early childhood. The syndrome was first described in 1974 by Alfried Kohlschütter and colleagues. Only 24 affected individuals are known as of 2012. The disease has not been connected to any other known epileptic syndromes. Some but not all cases are associated with mutations in a gene called ROGDI. Another gene that has been associated with this condition is the SCL13A5 gene Diagnoses of this syndrome have occurred in Switzerland, Sicily, the Northern Israel Druze community as well as some other parts of Western Europe.

The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.

Inborn errors of metal metabolism refers to metabolic disturbances in the processing or distribution of dietary minerals.

An example is hemochromatosis.

The symptoms of Freeman–Sheldon syndrome include drooping of the upper eyelids, strabismus, low-set ears, a long philtrum, gradual hearing loss, scoliosis, and walking difficulties. Gastroesophageal reflux has been noted during infancy, but usually improves with age. The tongue may be small, and the limited movement of the soft palate may cause nasal speech. Often there is an H- or Y-shaped dimpling of the skin over the chin.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a "primary" immunodeficiency, the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 100 recognized PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, autoinflammatory disorders, tumors, and disorders of various organs. There are currently no cures for these conditions; treatment is palliative and consists of managing infections and boosting the immune system.

Type 1 vWD (60-80% of all vWD cases) is a quantitative defect which is heterozygous for the defective gene. It can arise from failure to secrete vWF into the circulation or from vWF being cleared more quickly than normal. Decreased levels of vWF are detected at 20-50% of normal, i.e. 20-50 IU.

Many patients are asymptomatic or may have mild symptoms and not have clearly impaired clotting, which might suggest a bleeding disorder. Often, the discovery of vWD occurs incidentally to other medical procedures requiring a blood work-up. Most cases of type 1 vWD are never diagnosed due to the asymptomatic or mild presentation of type I and most people usually end up leading a normal life free of complications, with many being unaware that they have the disorder.

Trouble may, however, arise in some patients in the form of bleeding following surgery (including dental procedures), noticeable easy bruising, or menorrhagia (heavy menstrual periods). The minority of cases of type 1 may present with severe hemorrhagic symptoms.

The various types of vWD present with varying degrees of bleeding tendency, usually in the form of easy bruising, nosebleeds, and bleeding gums. Women may experience heavy menstrual periods and blood loss during childbirth.

Severe internal bleeding and bleeding into joints are uncommon in all but the most severe type, vWD type 3.