Gaucher's Disease
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Gaucher's disease or Gaucher disease () (GD) is a
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...
in which glucocerebroside (a
sphingolipid Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sp ...
, also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising,
fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...
,
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
, low blood platelet count and enlargement of the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
and
spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...
, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as glucosylceramidase), which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s ( mononuclear leukocytes, which is often a target for intracellular parasites). Glucocerebroside can collect in the
spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...
,
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
,
kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
s,
lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...
s,
brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
, and
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
. Manifestations may include enlarged spleen and liver, liver malfunction, skeletal disorders or bone lesions that may be painful, severe
neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
complications, swelling of
lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s and (occasionally) adjacent joints, distended abdomen, a brownish tint to the skin,
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
, low blood
platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
count, and yellow fatty deposits on the white of the eye (
sclera The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective outer layer of the eye containing mainly collagen and some crucial elastic fiber. In the development of t ...
). Persons seriously affected may also be more susceptible to infection. Some forms of Gaucher's disease may be treated with enzyme replacement therapy. The disease is caused by a recessive mutation in the ''GBA'' gene located on chromosome 1 and affects both males and females. About one in 100 people in the United States are carriers of the most common type of Gaucher disease. The carrier rate among
Ashkenazi Jews Ashkenazi Jews ( ; also known as Ashkenazic Jews or Ashkenazim) form a distinct subgroup of the Jewish diaspora, that emerged in the Holy Roman Empire around the end of the first millennium CE. They traditionally speak Yiddish, a language ...
is 8.9% while the birth incidence is 1 in 450. Gaucher's disease is the most common of the lysosomal storage diseases. It is a form of sphingolipidosis (a subgroup of lysosomal storage diseases), as it involves dysfunctional metabolism of sphingolipids. The disease is named after the French physician Philippe Gaucher, who originally described it in 1882.


Signs and symptoms

* Painless
hepatomegaly Hepatomegaly is enlargement of the liver. It is a non-specific sign (medicine), medical sign, having many causes, which can broadly be broken down into infection, hepatic tumours, and metabolic disorder. Often, hepatomegaly presents as an abdomin ...
and
splenomegaly Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulat ...
: the size of the spleen can be , as opposed to the normal size of . Splenomegaly may decrease the affected individual's capacity for eating by exerting pressure on the stomach. While painless, enlargement of the spleen increases the risk of splenic rupture. * Hypersplenism and pancytopenia, the rapid and premature destruction of blood cells, leads to
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
, neutropenia,
leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...
, and
thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...
(with an increased risk of
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
and
bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethr ...
). *
Cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
of the liver is rare. * Severe pain associated with joints and bones occurs, frequently presenting in hips and knees. * While Gaucher disease is a spectrum disorder, it can be split into Neuronopathic and non-neuronopathic forms.
Neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
symptoms occur only in some types of Gaucher's (see below): * Type II: Seizures, hypertonia, developmental delay, difficulty swallowing, apnea and other brainstem function abnormalities. * Type III: muscle twitches known as myoclonus, seizures, slowed horizontal saccadic eye movement, and in some cases, cognitive impairment. * Parkinson's disease is recognized as being more common in Gaucher's disease patients and their heterozygous carrier relatives. *
Osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...
: 75% of patients develop visible bony abnormalities due to the accumulated glucosylceramide. A deformity of the distal
femur The femur (; : femurs or femora ), or thigh bone is the only long bone, bone in the thigh — the region of the lower limb between the hip and the knee. In many quadrupeds, four-legged animals the femur is the upper bone of the hindleg. The Femo ...
in the shape of an
Erlenmeyer flask An Erlenmeyer flask, also known as a conical flask (British English) or a titration flask, is a type of laboratory flask with a flat bottom, a conical body, and a cylindrical neck. It is named after the German chemist Emil Erlenmeyer (1825–190 ...
is commonly described. * Yellowish-brown skin pigmentation


Genetics

The three types of Gaucher's disease are
autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
. Both parents must be carriers for a child to be affected. If both parents are carriers, the chance of the disease is one in four, or 25%, with each pregnancy for an affected child. Each type has been linked to particular mutations. In all, about 80 known ''GBA'' gene mutations are grouped into three main types: * Type I (N370S
homozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...
), the most common, also called the "non-neuropathic" type occurs mainly in
Ashkenazi Jews Ashkenazi Jews ( ; also known as Ashkenazic Jews or Ashkenazim) form a distinct subgroup of the Jewish diaspora, that emerged in the Holy Roman Empire around the end of the first millennium CE. They traditionally speak Yiddish, a language ...
, at 100 times the occurrence in the general populace. The median age at diagnosis is 28 years of age, and life expectancy is mildly decreased. * Type II (one or two
allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...
s L444P) is characterized by neurological problems in small children. The enzyme is hardly released into the
lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...
s. The prognosis is poor: most die before the age of three. * Type III (also one or two copies of L444P, possibly delayed by protective polymorphisms) occurs in Swedish patients from the Norrbotten region. This group develops the disease somewhat later, but most die before their 30th birthday. The Gaucher-causing mutations may have entered the Ashkenazi Jewish gene pool in the early Middle Ages (48–55 generations ago).


Pathophysiology

The disease is caused by a defect in the housekeeping gene for lysosomal glucocerebrosidase (also known as beta-glucosidase, , ) on the first
chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...
(1q22). The
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
is a 55.6- kilodalton, 497-
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
-long protein that catalyses the breakdown of glucocerebroside, a
cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
constituent of red and
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s. In Gaucher disease, the enzyme is unable to function correctly and glucocerebroside accumulates. The
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s that clear these cells are unable to eliminate the waste product, which accumulates in fibrils and turn into 'Gaucher cells', which appear on light microscopy to resemble crumpled-up paper. The exact mechanism of neurotoxicity is not understood, but it is thought to involve a reaction to glucosylsphingosine. Different mutations in the GBA (beta-glucosidase) gene determine the remaining activity of the enzyme. In type I, there is some residual activity of the enzyme, accounting for the lack of neuropathology in this type. Although there is some correlation between
genotype The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
and
phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
, neither the amount of stored lipids nor the residual enzyme activity correlates well with disease symptoms. This circumstance has called for alternative explanations accounting for disease symptoms including * jamming of the endo/lysosomal system * ER stress * altered lipid composition of membranes throughout the cell, including the plasma membrane, and consequent changes in the dynamic and signaling properties of the cell membrane * inflammation caused by cytokine secretion as a result of sphingolipid accumulation, and neurodegeneration caused by the accumulation of glucosylsphingosine, a
neurotoxin Neurotoxins are toxins that are destructive to nervous tissue, nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insult (medical), insultsSpencer 2000 that can adversely affect function ...
Heterozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...
s for particular acid beta-glucosidase mutations carry about a five-fold risk of developing
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
, making this the most common known genetic risk factor for Parkinson's. Cancer risk may be increased, particularly myeloma. This is thought to be due to accumulation of glucosylceramide and complex glycosphingolipids. The role of inflammatory processes in Gaucher disease is poorly elucidated. However, sphingolipids are known to participate in inflammation and
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
, and markers of macrophage activation are elevated in people with Gaucher disease. These markers include
angiotensin-converting enzyme Angiotensin-converting enzyme (), or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasocon ...
, cathepsin S, chitotriosidase, and CCL18 in the
blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...
; and tumor necrosis factor alpha in splenic Gaucher cells (engorged macrophages).


Diagnosis

Gaucher disease is suggested based on the overall clinical picture. Initial laboratory testing may include enzyme testing. As a result, lower than 15% of mean normal activity is considered to be diagnostic. Decreased enzyme levels will often be confirmed by genetic testing. Numerous different mutations occur; sequencing of the beta-glucosidase gene is sometimes necessary to confirm the diagnosis. Prenatal diagnosis is available and is useful when a known genetic risk factor is present. A diagnosis can also be implied by biochemical abnormalities such as high alkaline phosphatase,
angiotensin-converting enzyme Angiotensin-converting enzyme (), or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasocon ...
, and
immunoglobulin An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
levels, or by cell analysis showing "crinkled paper" cytoplasm and glycolipid-laden macrophages. Some lysosomal enzymes are elevated, including tartrate-resistant acid phosphatase, hexosaminidase, and a human chitinase, chitotriosidase. This latter enzyme has proved to be very useful for monitoring Gaucher's disease activity in response to treatment and may reflect the severity of the disease


Classification

Gaucher's disease (GD) has three common clinical subtypes. These subtypes have come under some criticism for not taking account of the full spectrum of observable symptoms (the
phenotypes In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological properti ...
). Also, compound heterozygous variations occur which considerably increase the complexity of predicting disease course. GD type I (non-neuropathic) is the most common and least severe form of the disease. Symptoms may begin early in life or adulthood and mainly affect the liver, spleen, and bone. Enlarged liver and grossly enlarged spleen (together hepatosplenomegaly) are common; the spleen can rupture and cause additional complications. Skeletal weakness and bone disease may be extensive. Spleen enlargement and bone marrow replacement cause anemia, thrombocytopenia, and
leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...
. The brain and nervous system are not affected pathologically, but lung and, rarely, kidney impairment may occur. Patients in this group usually
bruise A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur c ...
easily (due to low levels of platelets) and experience fatigue due to low numbers of red blood cells. Depending on disease onset and severity, type I patients may live well into adulthood. The range and severity of symptoms can vary dramatically between patients. GD type II (acute infantile neuropathic) typically begins within six months of birth and has an incidence rate of around 1 in 100,000 live births. Symptoms include an enlarged liver and spleen, extensive and progressive brain damage, eye movement disorders,
spasticity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...
,
seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
s, limb rigidity, and a poor ability to suck and swallow. Affected children usually die by age two. GD type III (chronic neuropathic) can begin at any time in childhood or even in adulthood and occurs in about 1 in 100,000 live births. It is characterized by slowly progressive, but milder neurologic symptoms compared to the acute or type II version. Major symptoms include an enlarged spleen and/or liver, seizures, poor coordination, skeletal irregularities, eye movement disorders, blood disorders including anemia, and respiratory problems. Patients often live into their early teen years and adulthood.


Treatment

For those with type-I and most type-III, enzyme replacement treatment with
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
recombinant glucocerebrosidase can decrease liver and spleen size, reduce skeletal abnormalities, and reverse other manifestations. This treatment costs about US$200,000 annually for a single person and should be continued for life. The rarity of the disease means dose-finding studies have been difficult to conduct, so controversy remains over the optimal dose and dosing frequency. Due to the low incidence, this has become an
orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...
in many countries, meaning a government recognizes and accommodates the financial constraints that limit research into drugs that address a small population. The first drug for Gaucher's was alglucerase (Ceredase), which was a version of glucocerebrosidase that was harvested from human
placental Placental mammals (infraclass Placentalia ) are one of the three extant subdivisions of the class Mammalia, the other two being Monotremata and Marsupialia. Placentalia contains the vast majority of extant mammals, which are partly distinguished ...
tissue and then modified with enzymes. It was approved by the FDA in 1991 and has been withdrawn from the market due to the approval of similar drugs made with
recombinant DNA Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
technology instead of being harvested from tissue; drugs made recombinantly are preferable since there is no concern about diseases being transmitted from the tissue used in harvesting, there are fewer risks of variations in enzyme structure from batch to batch, and they are less expensive to manufacture. Available recombinant glucocerebrosidases are: * Imiglucerase (approved in 1995) * Velaglucerase (approved in 2010) * Taliglucerase alfa (Elelyso) (approved in 2012) Miglustat is a small molecule, oral medication that was first approved for Gaucher's disease in Europe in 2002. It works by preventing the formation of glucocerebroside, the substance that builds up and causes harm in Gaucher's. This approach is called substrate reduction therapy.European Medicines Agency 1 April 200
Scientific discussion related to approval of Zavesca
.
Eliglustat (Cerdelga) (approved in 2014) is also a small molecule. The compound is believed to work by inhibition of glucosylceramide synthase.


Epidemiology

The National Gaucher Foundation (United States) states the incidence of Gaucher's disease is about one in 20,000 live births. Around one in 100 people in the general US population is a carrier for type I Gaucher's disease, giving a prevalence of one in 40,000. Among Ashkenazi Jews, the rate of carriers is considerably higher, at roughly one in 15. Type II Gaucher's disease shows no particular preference for any ethnic group. Type III Gaucher's disease is especially common in the population of the northern Swedish region of Norrbotten, where the incidence of the disease is one in 50,000.


History

The disease was first recognized by the French doctor Philippe Gaucher, who originally described it in 1882 and lent his name to the condition. In 1902, its mode of inheritance was discovered by Nathan Brill. The neuronal damage associated with the disease was discovered in the 1920s, and the biochemical basis for the disease was elucidated in the 1960s by
Roscoe Brady Roscoe Owen Brady (October 11, 1923 – June 13, 2016) was an American biochemist. He attended the Pennsylvania State University and obtained his M.D. degree from Harvard Medical School in 1947. He interned at the Hospital of the University of P ...
. The first effective treatment for the disease, the drug alglucerase (Ceredase), was approved by the FDA in April 1991. An improved drug, imiglucerase (Cerezyme), was approved by the FDA in May 1994 and has replaced the use of Ceredase. October is National Gaucher's Disease Awareness Month in the United States.


Society and culture


Prominent people with disease

* Wallace Chapman; New Zealand radio and television personality * Anne Begg; Scottish politician


See also

* Lysosomal storage disease * Niemann–Pick disease * Fabry disease *
Tay–Sachs disease Tay–Sachs disease is an Genetic disorder, inherited fatal lysosomal storage disease that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent arou ...
* Krabbe disease * Metachromatic leukodystrophy * Medical genetics of Ashkenazi Jews *
List of radiographic findings associated with cutaneous conditions Many conditions of or affecting the human integumentary system have associated features that may be found by performing an x-ray or CT scan of the affected person. See also * List of cutaneous conditions * List of contact allergens * List of ...


References


External links

* {{DEFAULTSORT:Gaucher's Disease Autosomal recessive disorders Lipid storage disorders Rare diseases Skin conditions resulting from errors in metabolism Diseases named after discoverers