TaoMedAI/RareMedData huggingface dataset:
Serine biosynthesis pathway deficiency, infantile/juvenile form (ORPHA:583595)
A rare inborn error of metabolism comprising 3-phosphoglycerate dehydrogenase deficiency, 3-phosphoserine phosphatase deficiency, and phosphoserine aminotransferase deficiency, and characterized by a phenotypic spectrum ranging from congenital microcephaly, psychomotor retardation, and intractable seizures in the infantile forms to milder juvenile forms with moderate developmental delay and intellectual disability.
SERKAL syndrome (ORPHA:139466)
SERKAL (SEx Reversion, Kidneys, Adrenal and Lung dysgenesis) syndrome is characterised by female to male sex reversal and developmental anomalies of the kidneys, adrenal glands and lungs.
Epidemiology
The syndrome is lethal and has been described in three foetuses.
Etiology
It is caused by homozygous missense mutations in the WNT4 gene.
Genetic counseling
It is transmitted as an autosomal recessive trait.

                            Last update: 
                            May 2008
Seronegative autoimmune hepatitis (ORPHA:563589)
A form of autoimmune hepatitis characterized by the features of classic autoimmune hepatitis (i. e. clinical presentation as acute or chronic cryptogenic hepatitis, interface hepatitis on histological examination, elevated serum aspartate aminotransferase and alanine aminotransferase levels, hypergammaglobulinemia/elevated immunoglobulin G, therapeutic response to corticosteroids) in the absence of serum autoantibodies. Clinical manifestations include fatigue, malaise, arthralgia, jaundice, at later stages also signs of advanced chronic liver disease, such as spider nevi, caput medusae, splenomegaly, ascites, and palmar erythema. Presence of concurrent autoimmune diseases is frequently observed.
Serotonin syndrome (ORPHA:43116)
A rare neurologic disease characterized by an excess of serotonin in the central nervous system, associated with the use of various agents, including selective serotonin reuptake inhibitors (SSRIs) and recreational stimulants.
Epidemiology
Data regarding prevalence in Europe are not available.
Clinical description
Serotoninergic syndrome may result in muscle rigidity, myoclonus, agitation, confusion, hyperthermia, hyperreflexia as well as dysautonomic symptoms, with a risk of shock with low peripheral vascular resistance, seizures, coma, rhabdomyolysis and/or disseminated intravascular coagulation (DIC).
Etiology
SSRIs and monoamine oxidase inhibitors (MAOIs) may be responsible for this syndrome at toxic but also at therapeutic concentrations. The syndrome may appear: a few hours to a few days after the initiation of the treatment; following simultaneous combination (counter-indication) of MAOIs-A (toloxatone, moclobemide) and SSRIs or successive combination with an excessively short pill-free interval; as the result of drug-drug interactions; or in some cases of acute poisoning. Individual susceptibility and severity of clinical effects may be explained by interindividual pharmacokinetic and pharmacodynamic differences. Various recreational stimulants including amphetamines (especially MDMA), synthetic cathinones, and cannabinoids are also increasingly involved.
Diagnostic methods
Diagnosis is based on clinical examination and compatible medical history. Additional investigations (electrocardiogram, laboratory examinations, toxicological analysis, electroencephalogram) are essential as clinical manifestations are not specific. Any acute infectious, neurological or metabolic diseases should be first excluded.
Differential diagnosis
Differential toxicological diagnoses include neuroleptic malignant syndrome, adrenergic or anticholinergic syndromes as well as alcohol withdrawal syndrome.
Management and treatment
Treatment is mainly supportive, based on sedation (benzodiazepines), mechanical ventilation, and even neuromuscular blockade, if necessary. In case of malignant hyperthermia, body cooling is mandatory. Dantrolene was proved inefficient. Cyproheptadine is the specific antidote for serotonin syndrome.
Prognosis
Prognosis is generally good if adequate supportive treatments are administered. However, deaths have been reported, due to multiorgan failure or brain anoxia.

                            Last update: 
                            January 2024


                            - Expert reviewer(s): 
                            Pr Bruno MÉGARBANE
Serotonin-producing neuroendocrine tumor of pancreas (ORPHA:506090)
A rare functioning neuroendocrine tumor of pancreas characterized by a typically well-differentiated neoplasm composed of cells expressing serotonin. Patients may present with atypical carcinoid syndrome with abdominal pain, diarrhea, weight loss, and/or flushing. Carcinoid syndrome is usually present only when there are liver metastases. The tumors tend to be larger than non-functioning tumors and are associated with a poorer prognosis because they are almost always metastatic.
Serous carcinoma of the corpus uteri (ORPHA:213726)
A rare high-grade endometrial carcinoma characterized by diffuse, marked nuclear pleomorphism, typically exhibiting complex papillary and/or glandular growth patterns and showing abnormal p53 and diffuse p16 immunohistochemistry. The tumor typically arises in atrophic endometrium or in an endometrial polyp. Most patients present with postmenopausal bleeding. Extrauterine metastasis is present in 40-50% of surgically staged cases, most frequently involving lymph nodes or peritoneal sites and omentum. Patients with extrauterine spread have poor outcomes, while endometrium-limited carcinoma has a better prognosis.
Serous cystadenocarcinoma of pancreas (ORPHA:424073)
A very rare, malignant, epithelial tumor of the pancreas composed of cystic structures lined by glycogen-rich clear cells, associated with local invasiveness often involving the spleen, duodenum and/or stomach and metastatic spread to the liver, peritoneum and/or lymph nodes. Presenting symptoms are variable and usually non-specific and include abdominal and/or flank pain, palpable abdominal mass, upper gastrointestinal bleeding, jaundice or abnormal serum liver enzymes, vomiting, anorexia and/or weight loss.
Serpiginous choroiditis (ORPHA:35686)
A rare non-infectious posterior uveitis characterized by usually bilateral, chronic, progressive, recurrent inflammation of the choroid, retinal pigment epithelium, and choriocapillaris. In the classic or peripapillary geographic type of the disease, infiltrates originating in the peripapillary region progress in an irregular serpentine fashion centrifugally and resolve spontaneously after several weeks, leaving atrophic scars. Multiple recurrences, often with months to years of quiescence in between, result in progressive visual loss in one or both eyes.
Serrated polyposis syndrome (ORPHA:157798)
A rare, genetic intestinal disease characterized by the presence of multiple (usually large) hyperplastic/serrated colorectal polyps, usually with a pancolonic distribution. Histology reveals hyperplastic polyps, sessile serrated adenomas (most common), traditional serrated adenomas or mixed polyps. It is associated with an increased personal and familial (first-degree relatives) risk of colorectal cancer.
SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome (ORPHA:597743)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by microcephaly, severe global developmental delay and intellectual disability, hypotonia, respiratory insufficiency, failure to thrive, and congenital anomalies affecting the skeleton, eyes, and several organ systems. Seizures and hearing loss are sometimes observed. Independent ambulation and meaningful speech are not attained. Common dysmorphic facial features include small forehead, biparietal narrowing, flat face, hypertelorism, arched eyebrows, short, upslanting palpebral fissures, wide nasal bridge, small, upturned nose, forward facing ears, and micrognathia. Brain imaging shows structural abnormalities in all patients.
Severe achondroplasia-developmental delay-acanthosis nigricans syndrome (ORPHA:85165)
Severe achondroplasia-developmental delay-acanthosis nigricans syndrome is characterised by the association of severe achondroplasia with developmental delay and acanthosis nigricans. It has been described in four unrelated individuals. Structural central nervous system anomalies, seizures and hearing loss were also reported, together with bowing of the clavicle, femur, tibia and fibula in some cases. The syndrome is caused by a Lys650Met substitution in the kinase domain of fibroblast growth factor receptor 3 (encoded by the FGFR3 gene; 4p16.3).
Severe acute respiratory syndrome (ORPHA:140896)
A rare pulmonary disease induced by SARS-CoV coronavirus infection, with a reported incubation period varying from 2 to 7 days. Patients present flu-like symptoms, including fever, malaise, myalgia, headache, diarrhoea, and rigors. Dry, nonproductive, cough and dyspnea are frequently reported. Severe cases evolve rapidly, progressing to respiratory distress and failure, requiring intensive care. Mortality rate is 10%. The disease appeared in 2002 in southern China, subsequently spreading in 2003 to 26 countries. Reported human-to-human transmission occurred in Toronto (Canada), Hong Kong Special Administrative Region of China, Chinese Taipei, Singapore, and Hanoi (Viet Nam).
Severe autosomal recessive macrothrombocytopenia (ORPHA:438207)
A rare isolated hereditary giant platelet disorder characterized by severe thrombocytopenia and thrombopathy due to defects in proplatelet formation and platelet activation in homozygous patients. Clinical manifestation are recurrent bleeding episodes including epistaxis, spontaneous hematomas, and menorrhagia.
Severe combined immunodeficiency due to adenosine deaminase deficiency (ORPHA:277)
Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is a form of SCID characterized by profound lymphopenia and very low immunoglobulin levels of all isotypes resulting in severe and recurrent opportunistic infections.
Epidemiology
SCID due to ADA deficiency accounts for 10-15% of all cases of SCID. Its annual incidence is estimated to be between 1/200,000 and 1/1,000,000 live births. Both males and females are affected.
Clinical description
SCID due to ADA deficiency has a variable clinical presentation. The most common form presents in infancy with severe and recurrent opportunistic infections (including respiratory tract infections and candidiasis), failure to thrive, and usually results in early death. Ten to 15% of patients have a delayed clinical onset by age 6-24 months, and a smaller percentage have a partial form of ADA deficiency with later onset between ages 4 years and adulthood, both types showing less severe infections and gradual immunologic deterioration. Patients may also present with extraimmune manifestations (including neurodevelopmental deficits, behavioral disorders, sensorineural deafness, and skeletal and hepatic abnormalities) as a result of the systemic nature of ADA expression.
Etiology
SCID due to ADA deficiency is caused by mutations in the ADA gene (20q13.11). The extraimmune manifestations are caused by toxic levels of purine metabolites that result from the deficiency of ADA.
Diagnostic methods
Diagnosis is based on evidence of low or undetectable ADA activity in erythrocytes in combination with evidence of a marked reduction of T, B and NK cell counts when compared to age-matched healthy controls. Diagnosis can be confirmed by raised levels of dATP and reduced S-adenosyl homocysteine hydrolase (SAHH) activity in red cells and elevated amounts of deoxyadenosine in urine.
Differential diagnosis
Differential diagnosis includes all forms of SCID.
Antenatal diagnosis
Prenatal diagnosis can be carried out through mutation analysis or measurement of enzyme activity in trophoblasts cultured from chorionic villus sampling or in cultured amniocytes.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Treatment is based on allogenic hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy with pegylated adenosine deaminase enzyme or gene therapy by infusion of CD34+ marrow cells that have been transduced with an ADA-containing vector.
Prognosis
Prognosis depends on the severity of the disease. Without treatment, SCID due to ADA deficiency that presents in infancy usually results in early death. Survival rates after allogenic hematopoietic stem cell transplantation or gene therapy are high.

                            Last update: 
                            July 2012


                            - Expert reviewer(s): 
                            Pr Andrew GENNERY
Severe combined immunodeficiency due to complete RAG1/2 deficiency (ORPHA:331206)
Severe combined immunodeficiency due to complete RAG1/2 deficiency is a rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia.
Severe combined immunodeficiency due to CORO1A deficiency (ORPHA:228003)
A rare T-B+ severe combined immunodeficiency characterized by profoundly decreased levels of T-cells, normal B-cells, and low immunoglobulin levels. The thymus is present. Patients typically become symptomatic in infancy or early childhood with recurrent infections. Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative syndrome/lymphoma and mucocutaneous-immunodeficiency syndrome have been reported in association. Some patients may show developmental delay, neurocognitive impairment, and behavioral dysfunction (in particular attention deficit-hyperactivity disorder).
Severe combined immunodeficiency due to CTPS1 deficiency (ORPHA:420573)
A rare primary immunodeficiency disorder due to impaired capacity of activated T- and B-cells to proliferate in response to antigen receptor-mediated activation characterized by early-onset, severe, persistent and/or recurrent viral infections due to Epstein-Barr virus (EBV) and Varicella Zoster virus (VZV, including generalized varicella), as well as recurrent sino-pulmonary bacterial infections due to encapsulated pathogens.
Severe combined immunodeficiency due to DCLRE1C deficiency (ORPHA:275)
Severe combined immunodeficiency (SCID) due to DCLRE1C deficiency is a type of SCID (see this term) characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation.
Epidemiology
Prevalence is unknown.
Clinical description
Patients present with the classical features of SCID such as failure to thrive, severe infections (pneumonia, gastrointestinal infections, sepsis), recurrent or persistent thrush, and chronic diarrhea. Materno-fetal transfusion-associated graft versus host disease is also associated with the disease. Immunological findings include absence of T and B lymphocytes with normal natural killer (NK) cell count.
Etiology
SCID due to DCLRE1C deficiency results from null mutations in the  DCLRE1C gene (10p13) that lead to a defect in the V(D)J recombination and thus to an early arrest of both B and T cell maturation.
Genetic counseling
Transmission is autosomal recessive.

                            Last update: 
                            March 2013


                            - Expert reviewer(s): 
                            Pr Andrew GENNERY
Severe combined immunodeficiency due to DNA-PKcs deficiency (ORPHA:317425)
Severe combined immunodeficiency (SCID) due to DNA-PKcs deficiency is an extremely rare type of SCID (see this term) characterized by the classical signs of SCID (severe and recurrent infections, diarrhea, failure to thrive), absence of T and B lymphocytes, and cell sensitivity to ionizing radiation.
Severe combined immunodeficiency due to FOXN1 deficiency (ORPHA:169095)
A rare, genetic, primary immunodeficiency due to a defect in adaptive immunity characterized by the triad of congenital athymia (resulting in severe T-cell immunodeficiency), congenital alopecia totalis and nail dystrophy. Patients present neonatal or infantile-onset, severe, recurrent, life-threatening infections and low or absent circulating T cells. Additional features reported include erythroderma, lymphoadenopathy, diarrhea and failure to thrive.
Severe combined immunodeficiency due to IKK2 deficiency (ORPHA:397787)
A rare, genetic form of primary immunodeficiency characterized by life-threatening bacterial, fungal and viral infections with the onset in infancy, and failure to thrive. Typically, hypogammaglobulinemia or agammaglobulinemia and normal levels of T and B cells are present.
Severe combined immunodeficiency due to LAT deficiency (ORPHA:504523)
A rare severe combined immunodeficiency characterized by T-cell lymphopenia and absent T-cell proliferative responses, and normal B-cell and natural killer cell counts. Patients present in the first months of life with severe recurrent infections, failure to thrive, hematologic autoimmune disorders, and/or lymphoproliferation with splenomegaly.
Severe combined immunodeficiency due to LCK deficiency (ORPHA:280142)
A rare, combined T- and B-cell immunodeficiency characterized by failure to thrive, severe diarrhea, opportunistic infections, and abnormal T-cell differentiation and function due to LCK deficiency, leading to an important risk factor for inflammation and autoimmunity.
Severe congenital hypochromic anemia with ringed sideroblasts (ORPHA:300298)
STEAP3/TSAP6-related sideroblastic anemia is a very rare severe non-syndromic hypochromic anemia, which is characterized by transfusion-dependent hypochromic, poorly regenerative anemia, iron overload, resembling non-syndromic sideroblastic anemia (see this term) except for increased erythrocyte protoporphyrin levels.
Epidemiology
It has been reported in 3 siblings to date.
Etiology
STEAP3/TSAP6-related sideroblastic anemia is caused by a nonsense heterozygous mutation in the STEAP3/TSAP6 gene. Transmission is most likely recessive with a low expression allele.

                            Last update: 
                            July 2013


                            - Expert reviewer(s): 
                            Pr Clara CAMASCHELLA
Severe congenital nemaline myopathy (ORPHA:171430)
Severe congenital nemaline myopathy is a severe form of nemaline myopathy (NM; see this term) characterized by severe hypotonia with little spontaneous movement in neonates.
Epidemiology
The annual incidence of NM has been estimated at 1/50,000 live births and the severe congenital form might represent 10-20% of all cases.
Clinical description
Neonates have sucking and swallowing difficulties, and gastroesophageal reflux, which leads to failure to thrive. Involvement of diaphragm and intercostal muscles contributes to respiratory insufficiency. Cardiomyopathy and arthrogryposis may occur.
Etiology
The ACTA1 (1q42.13) and NEB (2q22) genes are associated with this form of NM.
Genetic counseling
NM is transmitted in an autosomal recessive fashion or occurs sporadically.
Prognosis
Survival after infancy is rare.

                            Last update: 
                            October 2011


                            - Expert reviewer(s): 
                            Dr Monique RYAN
Severe congenital neutropenia due to G6PC3 deficiency (ORPHA:331176)
Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency is a rare, genetic, primary immunodeficiency disorder characterized by increased susceptibility to recurrent, life-threatening bacterial infections, in association with typically severe neutropenia in peripheral blood and bone marrow and a prominent ectatic superficial vein pattern, resulting from recessively inherited mutations in the G6PC3 gene. Cardiac malformations (e.g. atrial septal defects, patent ductus arteriosus,valvular defects), urogenital anomalies (incl. cryptorchidism), growth and developmental delay, facial dysmorphism (e.g. frontal bossing, upturned nose, malar hypoplasia), and intermittent thrombocytopenia are frequently associated.
Severe congenital neutropenia due to JAGN1 deficiency (ORPHA:423384)
Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency is a rare, genetic, primary immunodeficiency disorder characterized by early-onset, recurrent, severe bacterial infections, granulopoiesis maturation arrest at the promyelocyte/myelocyte stage and markedly reduced absolute neutrophil counts, resulting from recessively inherited mutations in the JAGN1 gene. Mild facial dysmorphism (i.e. triangular face), short stature, failure to thrive, hypothyroidism, developmental delay, pancreatic insufficiency and coarctation of aorta, as well as bone and urogenital abnormalities, may also be associated.
Severe congenital neutropenia (ORPHA:42738)
Severe congenital neutropenia is an immunodeficiency characterized by low levels of granulocytes (< 200/mm3) without an associated lymphocyte deficit.
Epidemiology
The prevalence in the general population is estimated at 1-1.7/333,300. Annual incidence is around 1/250,000 births.
Clinical description
This neutropenia leads to repeated bacterial or mycotic infections in various locations, mostly cutaneo-mucous, ear, nose, and throat, and pulmonary. Stomatological signs are almost always present after 2 years of age and are distinguished by erosive gingivitis, hemorrhage and pain, associated with papilla on the tongue and mucous membranes. Infections may be very severe or even lethal. Around 15% of patients evolve to acute leukemia or a myelodysplastic syndrome.
Etiology
To date, mutations in four genes have been implicated in severe congenital neutropenia. These include the neutrophil elastase gene (ELA2), the GFI1 gene, the HAX1 gene and activation genes of Wiskott Aldrich disease (WASP). The combination of these mutations leads to a deficit in the production of neutrophils.
Diagnostic methods
The defining characteristic is cytology showing profound neutropenia associated with monocytosis. An isolated blockage at the promyelocyte stage of the myeloid series associated with eosinophilia and monocytosis is seen on myelogram.
Differential diagnosis
On the discovery of these features a complete biological assessment should be conducted to rule out several differential diagnoses, particularly lymphocytic immune deficiencies and autoimmune neutropenia.
Antenatal diagnosis
Prenatal diagnosis may be offered if the genotype is known.
Genetic counseling
The four mutations are transmitted differently: ELA2 and GFI1 are autosomal dominant, HAX1 is autosomal recessive, and WASP is X-linked recessive. Genetic counseling is essential and should take into account family history and the causal mutation.
Management and treatment
All febrile episodes or infections should be reviewed by a hospital and treated actively. Prophylactic antibiotics are used to prevent infections. If this is ineffective, hematopoietic growth factors (G-CSF in particular) can correct both neutropenia and the susceptibility to infections and can be administered either in response to infections or continuously. The dose of G-CSF required varies greatly. Continuous high dose G-CSF (more than 20µg/kg/day) encourages the onset of leukemia in the long term and therefore, in cases requiring continuous high dose treatment, bone marrow transplant should be considered.
Prognosis
The prognosis depends heavily on the quality of care and timeliness of treatment of severe infections, but also on the possibility of a bone marrow transplant, particularly in cases with malignant transformation.

                            Last update: 
                            July 2007


                            - Expert reviewer(s): 
                            Dr Jean DONADIEU