TaoMedAI/RareMedData huggingface dataset:
Galactosemia (ORPHA:352)
Galactosemia is a group of rare genetic metabolic disorders characterized by impaired galactose metabolism resulting in a range of variable manifestations encompassing a severe, life-threatening disease (classic galactosemia), a rare mild form (galactokinase deficiency) causing cataract, and a very rare form with variable severity (galactose epimerase deficiency) resembling classic galactosemia in the severe form (see these terms).
Epidemiology
Overall prevalence is unknown. The annual incidence of classic galactosemia is estimated to be between 1/40,000 and 1/60,000 in Western countries. Incidence appears to be variable in other ethnic groups with a higher rate reported in the Irish Traveler population possibly due to consanguinity.
Clinical description
Infants usually develop feeding difficulties, poor weight gain and growth, lethargy, and jaundice in the common severe form of the disorder, i.e. classic galactosemia. The rare, less severe clinical subtype of galactosemia (galactokinase deficiency) causes primarily cataracts while other signs of galactosemia are absent. The very rare subtype (galactose epimerase deficiency) has a variable clinical picture including the usual signs of galactosemia (hypotonia, poor feeding, vomiting, weight loss, jaundice) and complications such as impaired growth, cognitive deficit and cataracts.
Etiology
The different galactosemia types are caused by mutations in the GALT, GALK1, and  GALE genes (9p13, 17q24, 1p36) coding for the three enzymes essential in galactose metabolism resulting in impairment of the Leloir galactose degradation metabolic pathway. All three diseases follow an autosomal recessive pattern of inheritance.

                            Last update: 
                            December 2011


                            - Expert reviewer(s): 
                            Pr M.E. [Estela] RUBIO-GOZALBO
Galactosialidosis (ORPHA:351)
Galactosialidosis is a lysosomal storage disease characterized by coarse facial features, macular ''cherry red spot'', and dysostosis multiplex. Clinical presentation can be heterogenous ranging from a severe, early-onset, rapidly progressive infantile form to late onset, slowly progressive juvenile/adult form.
Gallbladder neuroendocrine tumor (ORPHA:100086)
A rare, very aggressive neuroendocrine neoplasm characterized by the presence of nodular mass(es) arising from the neck, fundus or body of the gallbladder or by diffuse thickening of the gallbladder wall. Patients may be asymptomatic (diagnosed incidentally after surgical resection of the gallbladder) or may present epigastric pain, abdominal mass and/or non-specific symptoms, such as nausea, jaundice, flushing, cough, wheezing, ascites, and anepithymia. Paraneoplastic syndromes, such as Cushing syndrome, hypercalcemia, acanthosis nigricans, bullous pemphigoid, dermatomyositis and the Leser-Trélat sign, may be associated.
Gamma-aminobutyric acid transaminase deficiency (ORPHA:2066)
A rare disorder of gamma-aminobutyric acid (GABA) metabolism characterized by a severe neonatal-infantile epileptic encephalopathy (manifesting with symptoms such as seizures, hypotonia, hyperreflexia and developmental delay) and growth acceleration.
Epidemiology
Five patients from three affected families have been reported in the literature to date.
Clinical description
Onset occurs in the neonatal/infantile period. Manifestations reported include hypotonia, impaired psychomotor development, hyperreflexia, lethargy, seizures, high-pitched cry, accelerated linear growth and developmental delay. The phenotype of GABA-T deficiency is more severe than what is seen in succinic semialdehyde dehydrogenase (SSADH) deficiency (see this term), although some patients have survived infancy but with severe neurodevelopmental impairment including myoclonic seizures and choreoathetosis.
Etiology
GABA-T deficiency is caused by a mutation in the ABAT gene (16p13.2) encoding mitochondrial 4-aminobutyrate aminotransferase (GABA-T). GABA-T is responsible for catalyzing the conversion of gamma-aminobutyrate to succinate semialdehyde in the GABA metabolic pathway. A mutation in this gene leads to an increased accumulation of GABA in central nervous tissue, leading to encephalopathy.
Genetic counseling
GABA-T deficiency is inherited in an autosomal recessive manner.

                            Last update: 
                            February 2016


                            - Expert reviewer(s): 
                            Dr Mahsa PARVIZ  - Dr Phillip PEARL
Gamma-glutamyl transpeptidase deficiency (ORPHA:33573)
A disorder that is characterized by increased glutathione concentration in the plasma and urine.
Epidemiology
Gamma-glutamyl transpeptidase deficiency has been detected in seven patients in five families worldwide.
Clinical description
Five of the patients also had central nervous system involvement.
Etiology
Gamma-glutamyl transpeptidase catalyses the first step in the degradation of glutathione. No mutations have been identified in patients with gamma-glutamyl transpeptidase deficiency.
Diagnostic methods
The diagnosis is based on the finding of glutathionuria, elevated levels of glutathione in plasma and decreased activity of gamma-glutamyl transpeptidase in nucleated cells.
Genetic counseling
As the disease is transmitted as an autosomal recessive trait, patients should be offered genetic counseling.
Management and treatment
No specific treatment has been proposed or tested.
Prognosis
The prognosis of gamma-glutamyl transpeptidase deficiency is hard to predict as only seven patients have been described worldwide.

                            Last update: 
                            March 2007


                            - Expert reviewer(s): 
                            Dr Agne LARSSON  - Dr Ellinor RISTOFF
Gamma-heavy chain disease (ORPHA:100026)
A type of HCD characterized by the production of incomplete monoclonal gamma-heavy chains without associated light chains. The clinical presentation most commonly resembles that of patients with systemic lymphoproliferative/autoimmune diseases.
Epidemiology
The prevalence is unknown. There have only been about 120 cases reported in the worldwide literature but this condition is thought to be under-diagnosed.
Clinical description
Disease onset usually occurs between the ages of 40 and 90 years but the disease has also been seen in younger persons. Disseminated lymphoproliferative disease with lymphadenopathy, splenomegaly and hepatomegaly is the most common feature of gamma-HCD. Localized lymphoproliferative disease may be extramedullary (commonly cutaneous involvement) or may be located exclusively in the bone marrow. In other patients the disease can present with no apparent proliferative lymphoplasmacytic disease but instead an underlying autoimmune disorder such as rheumatoid arthritis, autoimmune hemolytic anemia or thrombocytopenic purpura (see these terms).
Etiology
The cause of gamma-HCD is unknown.
Diagnostic methods
The diagnosis of gamma-HCD is based on identification of free gamma-chains without associated light chains by immunofixation of serum and a concentrated urine specimen by using specific antisera. Patients presenting with a lymphoplasma-cell proliferative disorder should be evaluated for gamma-HCD. Immunofixation of serum and urine should be performed on patients with atypical lymphoplasma-cell proliferative disorders.
Management and treatment
Because gamma-HCD is a heterogenous condition, the choice of therapy should rely on the underlying disorder. In an asymptomatic patient with minimal lymphoid proliferation no treatment is recommended. Any associated autoimmune disease should be managed with standard therapy without taking into account the existence of the abnormal monoclonal component. Melphalan and prednisone are used if proliferation is mainly plasmacytic. Chlorambucil, cyclophosphamide and vincristine may be beneficial if there is evidence of a progressive lymphoproliferative process. Radiation therapy and surgical removal of extramedullary plasmacytomas can be curative in some cases.
Prognosis
Gamma-HCD has a highly variable clinical course and ranges from an asymptomatic, benign, or transient process to a rapidly progressive neoplasm leading to a very poor prognosis.

                            Last update: 
                            October 2011


                            - Expert reviewer(s): 
                            Pr Robert KYLE  - Dr Dietlind WAHNER-ROEDLER
Gamma-sarcoglycan-related limb-girdle muscular dystrophy R5 (ORPHA:353)
A subtype of autosomal recessive limb-girdle muscular dystrophy characterized by a childhood onset of progressive shoulder and pelvic girdle muscle weakness and atrophy frequently associated with calf hypertrophy, diaphragmatic weakness, and/or variable cardiac abnormalities. Mild to moderate elevated serum creatine kinase levels and positive Gowers sign are reported.
Gangliocytoma (ORPHA:251937)
A rare, mixed neuronal-glial tumor characterized by slow growth and irregular arrangement of neoplastic ganglion cells (large, multipolar dysplastic neurons) within stroma composed of non-neoplastic glial elements. Most commonly it occurs in temporal lobe, but it can be located throughout central nervous system. Clinical manifestations vary depending on the location and include seizures, increased intracranial pressure, cerebellar signs and focal neurologic deficits. Memory disturbances, cranial nerve palsies and psychiatric symptoms have also been reported.
Ganglioglioma (ORPHA:251949)
Ganglioglioma is a rare, usually benign, well-circumscribed, often cystic, mixed neuronal-glial tumor (composed of both neoplastic glial and ganglionic elements) which is typically located in the temporal lobe and rarely invades the surrounding tissue. Patients usually present with seizures refractory to medical treatment. Association with neurofibromatosis type I and tuberous sclerosis has been reported.
Ganglioneuroblastoma (ORPHA:251877)
Ganglioneuroblastoma is a rare type of primitive neuroectodermal tumor (PNET; see this term), affecting almost exclusively infants and young children under the age of 10, usually occurring in the posterior mediastinum, adrenal medulla and extra-adrenal retroperitoneum (but sometimes in the neck and pelvis), with metastasis most often presenting in the bones, and characterized clinically by pain, stridor, shortness of breath, peripheral neurological signs, superior vena cava syndrome and congenital Horner syndrome (see this term), depending on the location of the tumor.
Ganglioneuroma (ORPHA:251992)
Ganglioneuroma is a rare tumor of neuroepithelial tissue, a benign and well-differentiated tumor of neural crest origin, arising from the sympathetic nervous system and composed of ganglion cells and stromal Schwann cells. It can arise anywhere from the base of the skull to the pelvis, with the most frequent locations being the adrenal glands, retroperitoneum, posterior mediastinum and the pelvis, or, in rare cases, the central nervous system, heart, bones, intestine or other sites. It may be asymptomatic or present with various symptoms due to mass effect. Association with neurofibromatosis type I, multiple endocrine neoplasia type 2B and Turner syndrome was reported.
Gardner syndrome (ORPHA:79665)
Gardner syndrome is a severe form of familial adenomatous polyposis characterized by multiple adenomas in the colon and rectum associated with prominent extracolonic features including osteomas and multiple skin and soft tissue tumors.
Gastric adenocarcinoma and proximal polyposis of the stomach (ORPHA:314022)
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare hereditary gastric cancer characterized by proximal gastric polyposis and increased risk of early-onset, intestinal-type adenocarcinoma of the gastric body, with no duodenal or colorectal polyposis.
Gastrocutaneous syndrome (ORPHA:2069)
A rare, syndromic, hyperpigmentation of the skin characterized by multiple lentigines and café-au-lait spots associated with hiatal hernia and peptic ulcer, hypertelorism and myopia. There have been no further descriptions in the literature since 1982.
Gastrointestinal stromal tumor (ORPHA:44890)
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal (GI) tract, typically presenting in adults over the age of 40 (mean age 63), and only rarely in children, in various regions of the GI tract, most commonly the stomach or small intestine but also less commonly in the esophagus, appendix, rectum and colon. GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass, blood in stool, and intestinal obstruction. GISTs can also be seen in familial syndromes such as Carney triad and neurofibromatosis type 1.
Gastroschisis (ORPHA:2368)
A rare abdominal wall malformation characterized by the bowel protruding from the fetal abdomen on the right lateral base of the umbilical cord, and without a covering sac.
Epidemiology
In Europe, the average recorded prevalence of gastroschisis is 1/6,000 births with an increasing trend.
Clinical description
The disorder occurs around the tenth week of gestation, and results in bowel protruding, without a covering sac. If the defect is large enough, other viscera (stomach, bladder and gonads) might be exteriorized in some cases by the end of gestation. The liver always remains intra-abdominal. Intestinal damage, bowel atresia and even bowel perforation may occur as a result from the primary defect. When the hernia ring is tight or decreasing in size, necrosis or progressive ischemia of the protruding intestines may be observed, resulting in some cases with poorer prognosis. Intestinal lesions are linked to the quality of the mesenteric vascularization more than to the contact between intestinal loops and amniotic fluid. Other malformations are only exceptionally associated.
Etiology
Gastroschisis is believed to be a defect of the umbilical cord and ring, but the exact etiology remains unknown. Maternal age ( less than 20 years old) and maternal exposure to cigarette smoke could be risk factors. Genetic mutations and maternal genitourinary tract infections have been associated with an increased risk, but the exact pathological mechanisms remain elusive. Few familial cases have been reported.
Diagnostic methods
Diagnosis is usually made before birth during prenatal ultrasound (US) in the first trimester, allowing the birth to be arranged in a specialized unit where surgery can be performed immediately and intensive neonatal support is available.
Differential diagnosis
The only differential diagnosis is omphalocele which is more frequent, occurs earlier in embryonic development, and is associated in half of the cases with other malformations.
Antenatal diagnosis
Prenatal diagnosis is nowadays made in the first trimester, and relies on the picture of intestinal loops floating freely outside the abdominal cavity, to the right of the cord. Fetal karyotype is not mandatory. Later in gestation, the US scan focuses on fetal growth, amniotic fluid amount, thickness and diameter of both intra and extra abdominal loops.
Management and treatment
Gastroschisis is a surgical emergency. Primary abdominal closure is not always possible and different techniques of delayed management may be resorted to. Neonatal nutritional support is paramount. Early delivery is often proposed when intestinal complication is suspected.
Prognosis
Prognosis is linked to the functional quality of the intestinal loops, but is excellent in more than 90% of cases.

                            Last update: 
                            March 2020


                            - Expert reviewer(s): 
                            Dr Sylvie BEAUDOIN
GATA2 deficiency spectrum (ORPHA:228423)
A rare genetic primary immunodeficiency characterized by profound circulating monocytopenia, B- and NK-cell lymphopenia and severe dentritic cell decrease, which manifests clinically with disseminated mycobacterial and viral infections, as well as opportunistic fungal and parasitic infections and frequent pulmonary alveolar proteinosis. Predisposition to developping myeloid neoplasms is associated.
Gaucher disease type 2 (ORPHA:77260)
Gaucher disease type 2 is the acute neurological form of Gaucher disease (GD; see this term). It is characterized by early-onset and severe neurological involvement of the brainstem, associated with an organomegaly and generally leading to death before the age of 2.
Epidemiology
The annual incidence of GD in the general population is around 1/60,000 and the prevalence is approximately 1/100,000. GD type 2 is very rare, with an incidence of approximately 5% of all GD patients and has a prevalence of virtually zero, taking into account its severity and early death.
Clinical description
The disease usually presents in infants aged 3 to 6 months with systemic manifestations of hepatosplenomegaly and an early onset and severe neurological syndrome. The first signs are oculomotor paralysis or bilateral fixed strabismus associated with bulbar signs, in particular severe swallowing difficulties, progressive spasticity and dystonic movements. Seizures occur later and manifest as myoclonic epilepsy that is refractory to treatment with antiepileptics.
Etiology
GD type 2 is a lysosomal storage disease caused by a mutation in the GBA gene (1q21) that codes for the lysosomal enzyme, glucocerebrosidase. The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramidase (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, of the spleen and the bone marrow (Gaucher cells).
Diagnostic methods
A definite diagnosis requires the demonstration of a deficit in the enzymatic activity of glucocerebrosidase.
Antenatal diagnosis
Biochemical prenatal diagnosis can be proposed to couples who have already had a child with GD type 2. It can be carried out by measuring the enzyme activity in chorionic villus samples at 10-12 weeks of pregnancy or in amniocytes in culture towards 16 weeks of pregnancy.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
The treatment does not seem to have an effect on neurological manifestations and is therefore not indicated for patients with GD type 2.
Prognosis
Prognosis is poor with most patients dying before the age of 2.

                            Last update: 
                            February 2012


                            - Expert reviewer(s): 
                            Dr Nadia BELMATOUG  - Dr Jérôme STIRNEMANN
Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome (ORPHA:2072)
Gaucher disease - ophthalmoplegia - cardiovascular calcification is a variant of Gaucher disease, also known as a Gaucher-like disease that is characterized by cardiac involvement.
Epidemiology
This syndrome is rare with less than 30 cases reported in the literature.
Clinical description
The principle manifestation is progressive calcification of the aorta, and of the aortic and/or mitral valves. Other common features include mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia.
Etiology
The disease is caused by homozygous D409H (1342G to C) mutations in the GBA gene (1q21) that encodes the lysosomal membrane-associated glycoprotein, glucosylceramidase. The enzyme deficiency resulting from the mutation leads to accumulation of glucosylceramide (GL1) and other glycolipids in the cells of the reticuloendothelial system.
Diagnostic methods
The diagnosis can be made by measuring glucosylceramidaseactivity and is confirmed by identification of the D409H GBA gene mutation.
Antenatal diagnosis
Prenatal diagnosis is possible through detection of the glucosylceramidase deficiency in amniocytes or chorionic villus samples, or through screening for the GBA gene mutation in families in which the D409H allele has been identified in both parents or an affected brother or sister.
Genetic counseling
The syndrome is transmitted in an autosomal recessive manner.
Management and treatment
Patients with this syndrome require close monitoring by echocardiography as the cardiac complications require aortic and mitral valve replacement. Enzyme substitution therapy, involving regular intravenous infusions of the recombinant glucosylceramidase enzyme, imiglucerase, has been used successfully in the treatment of this disorder following surgery.
Prognosis
The prognosis for patients depends on the outcome of the heart surgery.

                            Last update: 
                            February 2012


                            - Expert reviewer(s): 
                            Dr Nadia BELMATOUG  - Dr Jérôme STIRNEMANN
Gaucher disease (ORPHA:355)
Gaucher disease (GD) is a lysosomal storage disorder encompassing three main forms (types 1, 2 and 3), a fetal form and a variant with cardiac involvement (Gaucher disease - ophthalmoplegia - cardiovascular calcification or Gaucher-like disease).
Epidemiology
The prevalence is approximately 1/100,000. The annual incidence of GD in the general population is about 1/60,000, but it can reach up to 1/1,000 in Ashkenazi Jewish populations.
Clinical description
The clinical manifestations of this disease are highly variable. GD type 1 (90% of cases) is the chronic and non-neurological form associated with organomegaly (spleen, liver), bone anomalies (pain, osteonecrosis, pathological fractures) and cytopenia. Type 2, the acute neurological form, is characterized by early onset, rapidly progressing brainstem dysfunction, associated with organomegaly and leading to death before the age of 2. Type 3, the subacute neurological form, affects children or adolescents and is characterized by progressive encephalopathy (oculomotor apraxia, epilepsy and ataxia) with the systemic manifestations seen in type 1. The fetal form manifests with a decrease or absence of fetal movements or anasarca. Gaucher-like disease presents with progressive calcification of the aorta and the aortic and/ or mitral valves as its main feature.
Etiology
GD is due to mutations in the GBA gene (1q21) that codes for a lysosomal enzyme, glucocerebrosidase, or in very rare cases the PSAP gene that codes for its activator protein (saposin C). The deficiency in glucocerebrosidase leads to the accumulation of glucosylceramide (or beta-glucocerebrosidase) deposits in the cells of the reticuloendothelial system of the liver, the spleen and the bone marrow (Gaucher cells).
Diagnostic methods
Formal diagnosis of the disease is determined by the measurement of glucocerebrosidase levels in circulating leukocytes. Genotyping confirms the diagnosis.
Differential diagnosis
Differential diagnoses include other lysosomal storage disorders. The presence of Gaucher-like cells can be found in certain hematologic diseases (lymphoma, Hodgkin's lymphoma and chronic lymphocytic leukemia; see these terms).
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
There are two available treatments for GD type 1 and 3: enzyme substitution therapy (using imiglucerase or velaglucerase) and substrate reduction therapy (miglustat). These treatments are ineffective for GD type 2.
Prognosis
The prognosis is good in GD type 1. In type 2, death usually occurs before the age of 2. Without specific treatment, GD type 3 progresses to death within a few years.

                            Last update: 
                            February 2012


                            - Expert reviewer(s): 
                            Dr Nadia BELMATOUG  - Dr Jérôme STIRNEMANN
GCGR-related hyperglucagonemia (ORPHA:438274)
A rare tumor of pancreas caused by mutations in the GCGR gene characterized by pancreatic alpha cell hyperplasia, pancreatic neuroendocrine tumors and markedly increased serum glucagon levels in the absence of a glucagonoma syndrome. Clinical manifestations may include abdominal pain, pancreatitis, fatigue, diarrhea, and diabetes mellitus.