TaoMedAI/RareMedData huggingface dataset:
Glioblastoma (ORPHA:360)
Glioblastomas are malignant astrocytic tumors (grade IV according to the WHO classification).
Epidemiology
Glioblastomas represent the most frequent brain tumors in adults, with an annual incidence of around 1/33,330. Prevalence is estimated at 1/100,000.
Clinical description
They may occur at any age, but 70% of cases are seen in patients between 45 and 70 years of age. The tumors are usually located in the brain hemispheres, but can be found anywhere in the central nervous system. The disease often progresses rapidly (over 2 to 3 months), except when the glioblastoma develops within a pre-existing low grade astrocytoma (secondary glioblastoma). Neurological signs are nonspecific as they result from intracranial hypertension and include headaches and vomiting, often associated with behavioral changes or focal neurological deficits. Histological variants (gliosarcoma and giant cell glioblastoma) have been described for which the treatment protocols and prognosis are similar to those of glioblastoma.
Etiology
The cause of the disease is unknown, except when it occurs after therapeutic irradiation of the brain for another disease. The genetic abnormalities detected (amplification of the EGFR gene (7p12), mutations in the TP53 gene (17p13.1), loss of chromosome 10) vary depending on the nature of the tumor: primary glioblastoma (de novo) or a secondary glioblastoma (developing from a benign astrocytic tumor).
Diagnostic methods
Radiologic studies, computerized tomography (CT) and magnetic resonance imaging (MRI) demonstrate characteristic features such as an infiltrating tumor associated with heterogeneous contrast enhancement and areas of necrosis.
Differential diagnosis
The differential diagnosis should include infectious and parasitic diseases with central nervous system involvement. Familial forms of glioblastoma are very rare but the tumor may occur as part of a syndrome such as Turcot syndrome, neurofibromatosis type 1 or Li-Fraumeni syndrome (see these terms).
Management and treatment
The first-line treatment is usually surgery, either to confirm the diagnosis with a biopsy or to remove as much of the tumor as possible. Complete resection is rarely feasible, since tumor cells usually infiltrate the surrounding brain. Treatment is then completed with radiotherapy targeted at the tumor bed, combined with chemotherapy (nitrosoureas and temozolomide). In terms of survival, the benefits from adjuvant treatments after surgery are significant, although they remain modest. In case of relapse, second-line chemotherapy or reoperation may be performed. Due to the relative rarity of this tumor, management of glioblastoma patients should be carried out by multidisciplinary teams with expertise in neuro-oncology within prospective studies aiming to improve patient survival and quality of life.
Prognosis
Prognosis is poor, especially in the absence of gross total resection, in older patients and in case of severe neurological deficits.

                            Last update: 
                            November 2007


                            - Expert reviewer(s): 
                            Dr Jacques GRILL
Glioependymal/ependymal cyst (ORPHA:269197)
Glioependymal/ependymal cyst is a rare central nervous system malformation defined as a subarachnoid, supratentorial, interventricular or intraspinal, sometimes intracerebral or intramedullar cyst with an internal ependymal lining, possibly surrounded by glial tissue. It may be an incidental finding or may present at different ages with clinical features depending on its size and location. It may distort adjacent brain structures and cause macrocephaly, ventriculomegaly, hydrocephalus, focal neurological signs and other signs and symptoms. In some cases, it is associated with other cerebral malformations (e.g. corpus callosum agenesis, polymicrogyria, heterotopias).
Gliomatosis cerebri (ORPHA:251582)
A rare glial tumor characterized by extensive infiltration of the brain, often extending to infratentorial structures and even the spinal cord. The tumor corresponds to WHO grade III and is composed of elongated glial cells typically resembling astrocytes. Cases in which the predominant cell type is oligodendroglial have also been described. Some tumors develop a circumscribed neoplastic mass in addition to the diffuse lesion, usually showing features of high-grade glioma. Clinical symptoms include dementia, headache, seizures, signs of increased intracranial pressure, and a variety of neurological deficits. Prognosis is generally poor.
Global developmental delay-alopecia-macrocephaly-facial dysmorphism-structural brain anomalies syndrome (ORPHA:544488)
A rare disorder of ornithine metabolism characterized by global developmental delay, alopecia, macrocephaly, and dysmorphic facial features (including high and broad forehead, hypertelorism, ptosis, blepharophimosis, downslanting palpebral fissures, deep-set eyes, large ears, and retrognathia or high arched palate). Additional reported manifestations are sensorineural hearing loss, spasticity, hypotonia, hypoplastic nails, cryptorchidism, and clinodactyly, among others. Brain imaging may show white matter abnormalities, periventricular cysts, enlarged lateral ventricles, or prominent perivascular spaces.
Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome (ORPHA:404476)
Global developmental delay-lung cysts-overgrowth-Wilms tumor syndrome is a rare, genetic, overgrowth syndrome characterized by global developmental delay, macrosomia with subsequent somatic overgrowth, bilateral cystic lung lesions, congenital nephromegaly and bilateral Wilms tumor. Craniofacial dysmorphism includes macrocephaly, frontal bossing, large anterior fontanelle, mild hypertelorism, ear pit, flat nasal bridge, anteverted nares and mild micrognathia. Additional features may include brain and skeletal anomalies, enlarged protuberant abdomen, fat pads on dorsum of feet and toes, and rugated soles with skin folds, as well as umbilical/inguinal hernia and autistic behavior.
Global developmental delay-neuro-ophthalmological abnormalities-seizures-intellectual disability syndrome (ORPHA:488613)
A rare genetic neurological disorder characterized by infantile to childhood onset of global developmental delay, hypotonia, seizures, growth delay, and intellectual disability. Additional variable features include strabismus, cortical visual impairment, nystagmus, movement disorder (such as dystonia, ataxia, or chorea), or mild dysmorphic features, among others.
Global developmental delay-osteopenia-ectodermal defect syndrome (ORPHA:73223)
A rare genetic disease characterized by global developmental delay with language and cognition deficiencies, behavioral problems, osteopenia, joint laxity, skin defects consisting of hyperkeratosis and sweat gland and melanocyte abnormalities with hypopigmented areas, and abnormal hair structure. Mild facial dysmorphism (prominent forehead, thick eyebrows, epicanthal folds, broad nasal bridge, long philtrum, and micrognathia), abnormalities of the teeth, and skeletal and cardiac anomalies have also been described.
Global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome (ORPHA:480898)
Global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome is a rare, genetic, neurological disorder characterized by mild to severe developmental delay and speech impairment, truncal hypotonia, abnormalities of vision (including cortical visual impairment and abnormal visual-evoked potentials), progressive brain atrophy mainly affecting the cerebellum, and shortened or atrophic corpus callosum. Other clinical findings may include increased muscle tone in the extremities, dystonic posturing, hyporeflexia, scoliosis, postnatal microcephaly and variable facial dysmorphism (e.g. deep-set eyes, gingival hyperplasia, short philtrum and retrognathia).
Glomus tumor (ORPHA:391651)
A rare soft tissue tumor characterized by a nodular lesion composed of cells closely resembling the modified smooth muscle cells of the normal glomus body. The tumors most often arise in the skin or soft tissues of the distal extremities, in particular the subungual region, but have been reported in almost any location. They occur as typical glomus tumors, glomangiomatosis (multiple nodules of solid glomus tumor investing the vascular walls), symplastic (showing striking nuclear atypia without mitotic activity or necrosis) or malignant glomus tumors, and glomus tumors of uncertain malignant potential.
Glossopalatine ankylosis (ORPHA:141163)
A rare oromandibular-limb hypogenesis syndrome (OLHS) characterised by the presence of an intraoral band of variable thickness attaching the tongue to the hard palate or maxillary alveolar ridge. It may be associated with other abnormalities such as cleft palate (in which case the tongue may be attached to the nasal septum), mandibular hypoplasia, upper-lip hypoplasia, hypodontia and variable limb anomalies (e.g. oligodactyly, syndactyly and polydactyly).
Glossopharyngeal neuralgia (ORPHA:221098)
A rare cranial neuralgia characterized by paroxysmal, usually unilateral stabbing pain within the sensory distributions of the auricular and pharyngeal branches of the glossopharyngeal and sometimes the vagus nerve (i. e. the posterior part of the tongue, the tonsillar fossa, oropharynx, larynx, angle of the mandible, and/or ear). The attacks last seconds to minutes with intervals between the paroxysms ranging from a few minutes to a few hours, and appear in clusters lasting weeks to months, again with irregular intervals in between. Pain attacks are usually triggered by a specific stimulus but may also occur spontaneously. The condition can sometimes be associated with bradycardia, syncope, seizures, and even asystole, and is then termed vagoglossopharyngeal neuralgia.
Glutamate-cysteine ligase deficiency (ORPHA:33574)
A disorder that is principally characterized by hemolytic anemia, (usually rather mild), however, the presence of neurological symptoms has also been reported.
Epidemiology
Gamma-glutamylcysteine synthetase deficiency has been detected in nine patients from seven families worldwide.
Etiology
Gamma-glutamylcysteine synthetase catalyses the first and rate-limiting step in the synthesis of glutathione. Its deficiency results in low cellular levels of glutathione and gamma-glutamylcysteine. Four different mutations in the heavy subunit have been identified in four families affected by gamma-glutamylcysteine synthetase deficiency.
Diagnostic methods
The diagnosis consists of the following stages: clinical findings, the finding of low cellular levels of glutathione, low activity of gamma-glutamylcysteine synthetase, and mutation analysis of the gamma-glutamylcysteine synthetase genes.
Differential diagnosis
The differential diagnosis should include glutathione synthetase deficiency (see this term), which is also associated with low levels of glutathione.
Antenatal diagnosis
Antenatal diagnosis could be performed by measurement of gamma-glutamylcysteine synthetase activity or mutational analysis (if the mutation in the family is known) of chorionic villi samples or cultured amniocytes.
Genetic counseling
As transmission is autosomal recessive, families should be referred for genetic counselling.
Management and treatment
Patients with gamma-glutamylcysteine synthetase deficiency should avoid drugs known to precipitate hemolytic crises in patients with glucose-6-phosphate dehydrogenase deficiency, e.g. phenobarbital, acetylsalicylic acid and sulfonamides. It is possible that patients would benefit from treatment with anti-oxidants but no studies have been made.
Prognosis
The prognosis is difficult to predict, as only nine patients are known worldwide.

                            Last update: 
                            March 2007


                            - Expert reviewer(s): 
                            Dr Agne LARSSON  - Dr Ellinor RISTOFF
Glutaric acidemia type 3 (ORPHA:35706)
A rare inborn error of metabolism characterized by abnormally high urinary excretion of glutaric acid due to peroxisomal glutaryl-CoA oxidase deficiency. There is no association with a specific clinical phenotype.
Glutathione synthetase deficiency (ORPHA:32)
A rare disorder characterised by hemolytic anemia, associated with metabolic acidosis and 5-oxoprolinuria in moderate forms, and with progressive neurological symptoms and recurrent bacterial infections in the most severe forms.
Epidemiology
This disease has been detected in at least 70 patients in more than 50 families worldwide.
Etiology
Several mutations have been identified in the gene encoding glutathione synthetase, localized to chromosome 20q11.2. Glutathione synthetase catalyses the last step in the synthesis of glutathione and a deficiency results in low levels of glutathione. Acidosis is due to reduced feedback inhibition of gamma-glutamyl cysteine synthetase in the gamma-glutamyl cycle, which ultimately leads to overproduction and accumulation of 5-oxoproline.
Diagnostic methods
The diagnosis usually involves the following: clinical findings, the finding of 5-oxoprolinuria, low levels of glutathione, low activity of glutathione synthetase, and mutation analysis of the glutathione synthetase gene.
Differential diagnosis
Other causes of 5-oxoprolinuria include 5-oxoprolinase deficiency (see this term), diet (certain infant formulas and tomato juice), severe burns, Stevens-Johnson syndrome (see this term), inborn errors of metabolism not involving the gamma-glutamyl cycle, e.g. X-linked ornithine trancarbamylase deficiency, urea cycle defects, tyrosinemia, as well as homocystinuria (see these terms), drug metabolism (paracetamol, vigabatrin, flucloxacillin, netimicin), prematurity, malnutrition, pregnancy and nephropatic cystinosis.
Antenatal diagnosis
Antenatal diagnosis is possible.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Management includes correction of the acidosis, supplementation with antioxidants and avoidance of drugs known to precipitate hemolytic crises in patients with glucose-6-phosphate dehydrogenase deficiency, e.g. phenobarbital, acetylsalicylic acid and sulfonamides.
Prognosis
A long-term follow up study of 28 patients with glutathione synthetase deficiency has showed that the factors most predictive of survival and long-term outcome are early diagnosis, correction of acidosis and early supplementation with vitamin C and vitamin E.

                            Last update: 
                            March 2007


                            - Expert reviewer(s): 
                            Dr Agne LARSSON  - Dr Ellinor RISTOFF
Glycerol kinase deficiency, adult form (ORPHA:284414)
A rare form of glycerol kinase deficiency (GKD) characterized by pseudohypertriglyceridemia in otherwise healthy adults and diagnosed fortuitously.
Glycerol kinase deficiency, juvenile form (ORPHA:284411)
Juvenile glycerol kinase deficiency (GKD) is an uncommon form of GKD (see this term) characterized by Reye-like clinical manifestations including episodic vomiting, acidemia, and disorders of consciousness.
Glycogen storage disease due to acid maltase deficiency, infantile onset (ORPHA:308552)
Glycogen storage disease due to acid maltase deficiency, infantile onset is the most severe form of glycogen storage disease due to acid maltase deficiency, characterized by cardiomegaly with respiratory distress, muscle weakness and feeding difficulties. It is often fatal.
Glycogen storage disease due to acid maltase deficiency, late-onset (ORPHA:420429)
A rare form of glycogen storage disease due to acid maltase deficiency characterized by excessive accumulation of glycogen in lysosomes most notably in skeletal muscle, leading to slowly progressive muscle weakness with walking disability and reduced respiratory function. The late-onset form includes all cases in which hypertrophic cardiomyopathy did not manifest or was not diagnosed at or under the age of 1 year, as well as all cases with symptom onset above the age of 1 year.
Glycogen storage disease due to acid maltase deficiency (ORPHA:365)
A rare lysosomal storage disease characterized by lysosomal accumulation of glycogen particularly in skeletal, cardiac, and respiratory muscles, as well as the liver and nervous system, due to acid maltase deficiency. The clinical spectrum comprises infantile-onset disease with severe hypertrophic cardiomyopathy, generalized muscle weakness, poor feeding and failure to thrive, and respiratory insufficiency, and late-onset disease manifesting before or after twelve months of age without cardiomyopathy, with proximal muscle weakness and respiratory insufficiency.
Glycogen storage disease due to aldolase A deficiency (ORPHA:57)
Glycogen storage disease due to aldolase A deficiency is an extremely rare glycogen storage disease (see this term) characterized by hemolytic anemia with or without myopathy or intellectual deficit. Myopathy can be severe enough to result in fatal rhabdomyolysis in some patients. A family with episodic rhabdomyolysis (triggered by fever) without hemolytic anemia has recently been reported.
Glycogen storage disease due to glucose-6-phosphatase deficiency type Ia (ORPHA:79258)
Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type a, or glycogen storage disease (GSD) type 1a, is a type of glycogenosis due to G6P deficiency (see this term).
Epidemiology
Prevalence is unknown. Annual incidence at birth of glycogenosis due to G6P deficiency is around 1/100,000. Type a is the more frequent type, affecting about 80% of patients.
Clinical description
The disease may manifest at birth by enlarged liver or, more commonly, between the ages of three to four months by symptoms of fast-induced hypoglycemia (tremors, seizures, cyanosis, and apnea). Patients present disturbed glucose homeostasis usually characterized by poor tolerance to fasting, significant hepatomegaly (sometimes eight to ten cm below the right costal margin), growth retardation (short stature and delayed puberty), generally improved by an appropriate diet, osteopenia and, in some cases, osteoporosis, round doll-like facial appearance with full cheeks, mild hypotonia, nephromegaly, and platelet dysfunction that may lead to frequent epistaxis. Diarrhea may be encountered. Late complications are hepatic (adenomas with rare but possible transformation into hepatocellular carcinoma) and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal failure), but also include anemia, sometimes severe, and a risk of hypoglycemic brain damage. Pulmonary hypertension has been reported in few cases.
Etiology
The disease is due to a dysfunction in the G6P system, a key step in glycemia regulation. Type a is due to mutations in the G6PC gene (17q21), which cause a deficit of the catalytic subunit G6P-alpha expressed in the liver, kidney and intestine. Many mutations have been identified, illustrating the allelic heterogeneity of the condition.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Management is similar in both types of glycogenosis due to G6P deficiency (see this term).

                            Last update: 
                            November 2010


                            - Expert reviewer(s): 
                            Pr Philippe LABRUNE
Glycogen storage disease due to glucose-6-phosphatase deficiency type Ib (ORPHA:79259)
Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type b, or glycogen storage disease (GSD) type 1b, is a type of glycogenosis due to G6P deficiency (see this term).
Epidemiology
Prevalence is unknown. Annual incidence at birth of glycogenosis due to G6P deficiency is around 1/100,000. Type b is the less frequent type, affecting about 20% of patients.
Clinical description
Clinical presentation is similar to that of glycogenosis due to G6P deficiency type a (see this term). In addition, in type b, neutropenia, and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphthous gingivostomatitis, and inflammatory bowel disease.
Etiology
The disease is due to a dysfunction in the G6P system, a key step in glycemia regulation. Type b is due to mutations in the SLC37A4 gene (11q23), which cause a deficit of the ubiquitously expressed G6P transporter, or G6P translocase (G6PT). Many mutations have been identified, illustrating the allelic heterogeneity of the condition.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Management is similar in both types of glycogenosis due to G6P deficiency (see this term). However, in type b, periodic antibiotic therapy may be needed, and, under careful monitoring, granulocyte colony-stimulating factor (G-CSF or GCSF) enables correction of neutropenia with reduction of infections and inflammatory bowel disease.

                            Last update: 
                            November 2010


                            - Expert reviewer(s): 
                            Pr Philippe LABRUNE
Glycogen storage disease due to glycogen branching enzyme deficiency (ORPHA:367)
Glycogen branching enzyme (GBE) deficiency (Andersen's disease or amylopectinosis), or glycogen storage disease type 4 (GSD4), is a rare and severe form of glycogen storage disease which accounts for approximately 3% of all the glycogen storage diseases (see these terms).
Clinical description
Clinical presentation is extremely heterogeneous and involves the liver or the neuromuscular system. In the classical form, children are normal at birth, but develop hepatomegaly, hypotonia, and developmental delay during their first months. The disease then rapidly progresses to cirrhosis with portal hypertension and ascites, ultimately causing death in early childhood. A non-progressing hepatic form has been reported in a few cases. In the neuromuscular presentation, the age of onset ranges from fetal to adult age. The most severe form starts before birth with decrease or absence of fetal movements, arthrogryposis, hypoplastic lungs, and perinatal death. Patients with congenital forms have severe hypotonia, cardiomyopathy, depressed respiration and neuronal involvement. Milder forms have been reported with later-onset, marked by muscular weakness or cardiomyopathy and heart failure. Neurological adult forms with central and peripheral nervous system dysfunction have also been described, such as Adult Polyglucosan Body Disease (APBD; see this term), which is characterized by widespread upper and lower motor neuron lesions.
Etiology
The disease is caused by mutations in the GBE1 gene (3p12) encoding GBE. GBE deficiency results in storage of abnormal glycogen that resembles an amylopectin-like structure (polyglucosan).
Diagnostic methods
The diagnosis is based on biochemical findings from a liver biopsy, revealing an abnormal glycogen content, and on the evidence of enzymatic deficiency in the liver, muscle, erythrocytes, or fibroblasts, and in the trophoblast or cultured amniotic cells.
Differential diagnosis
Differential diagnoses include galactosemia, hydrops fetalis, and tyrosinemia (see these terms).APBD can also present with or without GBE deficiency indicating that different biochemical defects could result in an identical phenotype.
Antenatal diagnosis
Prenatal diagnosis is possible by enzyme assay and/or DNA analysis.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
There is no specific treatment. A liver transplant can be proposed in severe forms without associated heart disease.
Prognosis
Prognosis is unfavorable for patients with perinatal onset and classic forms who do not undergo liver transplantation. Long-term prognosis for others depends on the extent, severity, and progression of the condition.

                            Last update: 
                            September 2009


                            - Expert reviewer(s): 
                            Dr Roseline FROISSART