Diseases

Hepatoerythropoietic porphyria

Hepatoerythropoietic porphyria: an autosomal recessive disorder in which there is a deficiency or absence of uroporphyrinogen decarboxylase; results in photosensitivity and excessive hepatic production of 8- and 7-carboxylate porphyrins. Source: Stedman's Medical Spellchecker, © 2006 Lippincott Williams & Wilkins. All rights reserved. Hepatoerythropoietic porphyria: An autosomal recessive cutaneous porphyria that is due to a deficiency of UROPORPHYRINOGEN DECARBOXYLASE in both the LIVER and the BONE MARROW. Similar to PORPHYRIA CUTANEA TARDA, this disorder is caused by defects in the fifth enzyme in the 8-enzyme biosynthetic pathway of HEME, but is a homozygous enzyme deficiency with less than 10% of the normal enzyme activity. Cutaneous lesions are severe and mutilating.

Hepatorenal syndrome

Hepatorenal syndrome (often abbreviated HRS) is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. HRS is usually fatal unless a liver transplant is performed, although various treatments, such as dialysis, can prevent advancement of the condition.

HRS can affect individuals with cirrhosis (regardless of cause), severe alcoholic hepatitis, or fulminant liver failure, and usually occurs when liver function deteriorates rapidly because of an acute insult such as an infection, bleeding in the gastrointestinal tract, or overuse of diuretic medications. HRS is a relatively common complication of cirrhosis, occurring in 18% of cirrhotics within one year of their diagnosis, and in 39% of cirrhotics within five years of their diagnosis. Deteriorating liver function is believed to cause changes in the circulation that supplies the intestines, altering blood flow and blood vessel tone in the kidneys. The kidney failure of HRS is a consequence of these changes in blood flow, rather than direct damage to the kidney. The diagnosis of hepatorenal syndrome is based on laboratory tests of individuals susceptible to the condition. Two forms of hepatorenal syndrome have been defined: Type 1 HRS entails a rapidly progressive decline in kidney function, while type 2 HRS is associated with ascites (fluid accumulation in the abdomen) that does not improve with standard diuretic medications.

The risk of death in hepatorenal syndrome is very high; the mortality of individuals with type 1 HRS is over 50% over the short term, as determined by historical case series. The only long-term treatment option for the condition is liver transplantation. While awaiting transplantation, people with HRS often receive other treatments that improve the abnormalities in blood vessel tone, including supportive care with medications, or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS), which is a small shunt placed to reduce blood pressure in the portal vein. Some patients may require hemodialysis to support kidney function, or a newer technique called liver dialysis which uses a dialysis circuit with albumin-bound membranes to bind and remove toxins normally cleared by the liver, providing a means of extracorporeal liver support until transplantation can be performed.

Hereditary amyloidosis

Hereditary amyloidosis is a condition in which abnormal protein deposits (called amyloid) form in almost every tissue in the body. These protein deposits damage the tissues and interfere with the function of the involved organs.

Hereditary angioedema

Hereditary angioedema is an immune disorder characterized by recurrent episodes of severe swelling. The most commonly affected areas of the body are the limbs, face, intestinal tract, and airway. HAE is caused by low levels or improper function of a protein called C1 inhibitor which affects the blood vessels. This condition is inherited in an autosomal dominant pattern.

There are three types of HAE, types I, II, and III. The types can be distinguished by their underlying causes and levels of C1 inhibitor in the blood. Type I and II are caused by mutations in the SERPING1 gene. Some cases of type III are associated with mutations in the F12 gene. Other genes are likely to be identified as the cause of other cases of HAE type III.

Hereditary ataxia

Hereditary ataxia: A group of rare genetic neuromuscular disorder involving degeneration of the brain and spinal cord.

Hereditary ATTR amyloidosis

hATTR amyloidosis is an inherited, rapidly progressive, life-threatening disease.1-3 hATTR amyloidosis is caused by a mutation in the transthyretin (TTR) gene that results in misfolded TTR proteins accumulating as amyloid fibrils in multiple tissues in the body, including the nerves, heart, and gastrointestinal tract.2,4,5

hATTR amyloidosis is an autosomal dominant disease; meaning a person only needs to inherit one copy of the affected gene from one parent in order to develop the condition. When one parent carries an autosomal dominant mutation, any child will have a 50% chance of inheriting that mutation.2,6

hATTR amyloidosis affects an estimated 50,000 people worldwide.5 In the disease continuum of hATTR amyloidosis some individuals present primarily with nerve-related symptoms, historically known as familial amyloidotic polyneuropathy (FAP).5,6 Others present primarily with heart-related symptoms, historically known as familial amyloidotic cardiomyopathy (FAC).5,6 More than half of people with hATTR amyloidosis present with a mix of both types of symptoms.7,8

The symptom presentation of hATTR amyloidosis is highly varied among individuals, even within the same mutation or the same family. In addition to the varied symptom presentation, the age of onset is wide-ranging – the median age is 39 years, with some people presenting as early as their 20s.6,9

Hereditary carnitine deficiency

Hereditary carnitine deficiency: An inherited deficiency of carnitine resulting primarily in muscle problems. Severe symptoms can be triggered by periods of illness or fasting.

Hereditary cerebral hemorrhage with amyloidosis

Cerebral hemorrhage with amyloidosis, hereditary, Dutch type: An inherited condition characterized mainly by brain hemorrhage and amyloid deposits in the brain blood vessels. The size and location of the hemorrhage determines the severity of symptoms. The condition was first described in a Dutch family.

Hereditary deafness

Alternative Names :Hereditary nephritis; Hematuria - nephropathy - deafness; Hemorrhagic familial nephritis; Hereditary deafness and nephropathy. Alport syndrome is an inherited disorder that leads to kidney damage.

Hereditary fructose intolerance

Alternative Names: Fructosemia; Fructose intolerance; Fructose aldolase B-deficiency; Fructose 1, 6 bisphosphate aldolase deficiency. Hereditary fructose intolerance is a disorder of metabolism in which a person lacks the protein needed to break down fructose. Fructose is a fruit sugar that naturally occurs in the body. Man-made fructose is used as a sweetener in many foods, including baby food and drinks.

Hereditary hearing disorder

Hereditary hearing disorder: Genetic disorders that affects hearing and is passed from parents to offspring.

Hereditary hearing loss

Hereditary hearing loss, also known as heriditary hearing impairment, or hereditary anacusis, is a partial or total inability to hear. An affected person may be described as hard of hearing. A deaf person has little to no hearing. Hearing loss may occur in one or both ears. In children hearing problems can affect the ability to learn language and in adults it can cause work related difficulties.

Hereditary Hemochromatosis

There are 4 types of hereditary hemochromatosis, types 1 through 4, depending on the gene that is mutated.

 

Type 1: Mutations of the HFE (human homeostatic iron regulator) gene

Type 2: (juvenile hemochromatosis): Mutations in the HJV (hemojuvelin BMP co-receptor) and HAMP (hepcidin antimicrobial peptide) genes

Type 3: Mutations in the TFR2 (transferrin receptor 2) gene

Type 4:(ferroportin disease): Mutations in the SLC40A1 (solute carrier family 40 member 1) gene

Other much rarer genetic disorders can cause hepatic iron overload, but the clinical picture is usually dominated by symptoms and signs due to failure of other organs (eg, anemia in hypotransferrinemia or atransferrinemia, or neurologic defects in aceruloplasminemia).

Although these types vary markedly in age of onset, clinical consequences of iron overload are the same in all types.

Type 1 hereditary hemochromatosis

 

Type 1 is classic hereditary hemochromatosis, also termed HFE-related hemochromatosis. More than 80% of cases are caused by the homozygous C282Y mutation or the C282Y/H63D compound heterozygote mutation. Homozygous H63D mutations occur rarely and have the same phenotype as homozygous C282y cases. The disorder is autosomal recessive, with a homozygous frequency of 1:200 and a heterozygous frequency of 1:8 in people of northern European ancestry. The C282Y and H63D mutations are uncommon among people with African ancestry and rare among people with Asian ancestry. Of patients with clinical features of hemochromatosis, 83% are homozygous. However, for unknown reasons, phenotypic (clinical) disease is much less common than predicted by the frequency of the gene (ie, many homozygous people do not manifest the disorder).

Type 2 hereditary hemochromatosis

 

Type 2 hereditary hemochromatosis (juvenile hemochromatosis) is a rare autosomal recessive disorder caused by mutations in the HJV gene that affect the transcription protein hemojuvelin, or mutations in the HAMP gene, which directly codes for hepcidin. It often manifests in adolescents.

Type 3 hereditary hemochromatosis

 

Mutations in transferrin receptor 2 (TFR2) gene that codes for a protein that appears to control saturation of transferrin, can cause a rare autosomal recessive form of hemochromatosis.

Type 4 hereditary hemochromatosis

 

Type 4 hereditary hemochromatosis (ferroportin disease) occurs largely in people of southern European ancestry. It results from an autosomal dominant mutation in the SLC40A1 gene and affects the ability of ferroportin to bind hepcidin.

Transferrin and ceruloplasmin deficiency

 

In transferrin deficiency (hypotransferrinemia or atransferrinemia), absorbed iron that enters the portal system not bound to transferrin is deposited in the liver. Subsequent iron transfer to sites of red blood cell production is reduced because of transferrin deficiency.

 

In ceruloplasmin deficiency (aceruloplasminemia), lack of ferroxidase causes defective conversion of Fe2+ to Fe3+; such conversion is necessary for binding to transferrin. Defective transferrin binding impairs the movement of iron from intracellular stores to plasma transport, resulting in accumulation of iron in tissues.

Hereditary hemorrhagic telangiectasia

Osler-Weber-Rendu syndrome. Alternative Names: Hereditary hemorrhagic telangiectasia Osler-Weber-Rendu syndrome is an inherited disorder of the blood vessels, which can cause excessive bleeding. The syndrome is also called hereditary hemorrhagic telangiectasia, or HHT.

Hereditary hyperuricemia

Hyperuricemia and gout have long been known to run in families. As well as an apparently multifactorial genetic component to classic gout itself, 2 rather unusual sex-linked single-gene disorders of purine biosynthesis or recycling have been defined: deficiency of the enzyme hypoxanthine-guaninephosphoribosyl transferase (HPRT), and overactivity of PPriboseP synthase. Both result in overproduction of urate, hyperuricemia, and secondary overexcretion that may lead to acute or chronic renal damage. Familial juvenile hyperuricemic nephropathy (FJHN) and autosomal-dominant medullary cystic kidney disease (ADMCKD) are more common but less well-defined hyperuricemic conditions resulting from a decrease in the fractional excretion of filtered urate, with normal urate production. Although having features in common, ADMCKD is distinguished in particular by the presence of medullary cysts. One major group of both disorders is associated with mutations in the gene for uromodulin, but this accounts for only about one third of cases, and genetic heterogeneity is present. Whether the genes involved in these latter disorders contribute to the polygenic hyperuricemia and urate underexcretion of classic gout remains unexplored.

Hereditary koilonychia

Hereditary koilonychia: An inherited anomaly where the nails are flattened or concave-shaped rather than the normal curved shape.

Hereditary macrothrombocytopenia

Hereditary macrothrombocytopenia: A rare inherited blood disorder where the blood platelets are abnormally large. Blood platelets are involved in the blood clotting process but patients with the condition often have no symptoms or suffer mild bleeding problems.

Hereditary methemoglobinemia- recessive

Autosomal recessive congenital methemoglobinemia is an inherited condition that affects the normal function of hemoglobulin (Hemoglobin carries oxygen to cells and tissues throughout the body). Methemoglobinemia, occurs when red blood cells (RBCs) contain methemoglobin at levels higher than 1%. Methemoglobin results from the presence of iron in the ferric form instead of the usual ferrous form. This results in a decreased availability of oxygen to the tissues, leading to a bluish appearance of the skin, lips, and nails (cyanosis).

There are four types of hereditary methemoglobinemias that are secondary to deficiency of NADH cytochrome b5 reductase, which is encoded by the CYB5R3gene. All of them are autosomal recessive disorders. Heterozygotes have 50% enzyme activity and no cyanosis; homozygotes that have elevated methemoglobin levels above 1.5% have clinical cyanosis. The four types are as follows:

  • Type I – This is the most common variant, and the enzyme deficiency is limited to the erythrocytes causing cyanosis; cyanosis usually, but not always, develops during infancy
  • Type II – Widespread deficiency of the enzyme occurs in various tissues, including erythrocytes, liver, fibroblasts, and brain; it is associated with severe CNS symptoms, including encephalopathy, microcephaly, hypertonia, athetosis, opisthotonos, strabismus, mental retardation, and growth retardation; cyanosis is evident at an early age
  • Type III – Although the hematopoietic system (platelets, RBCs, and white blood cells [WBCs]) is involved, the only clinical consequence is cyanosis
  • Type IV – Like type I, this type has isolated involvement of the erythrocytes but results in chronic cyanosis

Hereditary multiple exostoses

Hereditary multiple exostoses (HME or MHE), also known as Diaphyseal aclasis, is a rare medical condition in which multiple bony spurs or lumps (also known as exostoses, or osteochondromas) develop on the bones of a child. HME is synonymous with Multiple hereditary exostoses and Multiple osteochondromatosis, which is the preferred term used by the World Health Organization.

Hereditary myopathy with intranuclear filamentous

Hereditary myopathy with intranuclear filamentous, aka Inclusion body myositis (IBM) is one of a group of muscle diseases known as inflammatory myopathies, which are characterized by chronic muscle inflammation accompanied by muscle weakness. It is a slowly progressive disease, which causes a gradual deterioration of muscles that become thin and weak over the years. Most limb muscles can be affected. In particular the quadriceps (the thigh muscles which extend the knee joint), and forearm muscles that flex the wrists and fingers are commonly weak. Accordingly, patients often notice difficulty with stairs, getting out of a chair and a poor grip. Swallowing muscles are affected in some patients, but the disease typically does not affect muscles of the heart, eye, gut or bladder. It also does not affect the function of the brain or sensation, and speech is rarely affected. In general patients do not die of the disease, but most meet with some degree of disability as the disease progresses. The disease itself is painless. However, weakened muscles can predispose to injuries affecting bones, joints and soft tissues.

There are two types - sporadic inclusion body myositis (sIBM) and hereditary inclusion body myositis (hIBM)

In sIBM, two processes, one autoimmune and the other degenerative, appear to occur in the muscle cells in parallel. It usually occurs in middle to late life and is more common in men than women.

hIBM lacks some of the inflammatory characteristics of sporadic IBM. The disease develops in young adults and is caused by a wide range of genetic defects that can be passed between generations. Generally, these defects cause neuromuscular disorders characterized by muscle weakness. hIBM comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individual patients

 

Sources: Wikipedia, The Myositis Association; Medpedia; Muscular Dystrophy Campaign

Hereditary nodular heterotopia

Hereditary nodular heterotopia: A rare inherited disorder where a part of the brain tissue is misplaced during development.

Hereditary non-spherocytic hemolytic anemia

Hereditary non-spherocytic hemolytic anemia: A group of genetic blood disorders where red blood cells are prematurely destroyed resulting in anemia if they are not replaced fast enough. The blood cells are destroyed because they have abnormally weak membranes which gives them an irregular shape rather than normal doughnut shape.

Hereditary nonpolyposis colon cancer

Hereditary non-polyposis colorectal cancer (also known as HNPCC, Lynch syndrome, Familial non-polyposis colon cancer) is an inherited genetic condition, which accounts for 2-7% of all colorectal cancers.

HNPCC is divided into two types, type 1 (also known as Lynch syndrome I or familial colon cancer), where tumors localize exclusively in the colon and type 2 (Lynch syndrome II), associated with other cancers of the gastrointestinal or reproductive system (stomach, endometrium, ovary, and urinary tract).

 

Source:

Müller A, Fishel R. Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC). Cancer Invest. 2002;20(1):102-9.

University of California San Francisco (UCSF) Medical Center

 

 

Hereditary pancreatitis

Hereditary pancreatitis: A rare inherited condition involving recurring bouts of pancreatitis (inflammation of the pancreas) often leading to chronic pancreatitis due to scarring of the pancreas.

Hereditary paroxysmal cerebral ataxia

Acetazolamide-responsive, hereditary, paroxysmal, cerebellar ataxia (medical condition): A rare genetic disorder characterized by episodes of incoordination and unsteadiness as well as nystagmus (rapid, involuntary eye movements). Stress, exertion, alcohol and coffee may trigger the episodes which can last from hours to days. Type 2 is caused by a defect in the calcium ion gene on chromosome 19p13. Acetazolamide-responsive, hereditary, paroxysmal, cerebellar ataxia: Another name for Episodic ataxia, type 2 (or close medical condition association). Episodic ataxia, type 2: A rare genetic disorder characterized by episodes of incoordination and unsteadiness as well as nystagmus (rapid, involuntary eye movements). Stress, exertion, alcohol and coffee may trigger the episodes which can last from hours to days. Type 2 is caused by a defect in the calcium ion gene on chromosome 19p13.

Hereditary peripheral nervous disorder

Hereditary peripheral nervous disorder: A group of inherited disorders affecting the peripheral nerves (nerves other than the brain and spinal cord). The motor, sensory and/or autonomic nerves may be affected. Examples of such conditions includes Dejerine-Sottas disease and Charcot-Marie-Tooth disease.

Hereditary primary Fanconi disease

Hereditary primary Fanconi disease: A rare inherited disorder characterized by defective reabsorption of various substances such as phosphate, potassium, amino acids and glucose which manifests as a wide range of abnormalities and problems.