TaoMedAI/RareMedData huggingface dataset:
Mitochondrial myopathy and sideroblastic anemia (ORPHA:2598)
Mitochondrial myopathy and sideroblastic anemia belongs to the heterogeneous family of metabolic myopathies. It is characterised by progressive exercise intolerance manifesting in childhood, onset of sideroblastic anaemia around adolescence, lactic acidaemia, and mitochondrial myopathy.
Epidemiology
Less than 10 cases have been described so far.
Etiology
A 656C-->T mutation in the nuclear pseudouridine synthase 1 gene (PUS1), localised to 12q24.33, has recently been identified in some patients. Deficient pseudouridylation of mitochondrial tRNAs may be responsible for the oxidative phosphorylation disorder.
Diagnostic methods
Muscle biopsy demonstrates low activity of complexes 1 and 4 of the respiratory chain and paracrystalline inclusions can be revealed in most mitochondria by electron microscopy.
Genetic counseling
Transmission is autosomal recessive.

                            Last update: 
                            June 2006
Mitochondrial myopathy with reversible cytochrome C oxidase deficiency (ORPHA:254864)
A rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by a potentially life-threatening, severe myopathy manifesting in the neonatal to early infantile period, followed by marked, spontaneous improvement of muscular function by early childhood. Associated biochemical findings include lactic acidosis and a transient, marked decrease in respiratory chain activity.
Mitochondrial myopathy-lactic acidosis-deafness syndrome (ORPHA:2597)
A rare metabolic myopathy presenting during childhood, and characterized clinically by growth failure, severe muscle weakness, and moderate sensorineural deafness and biochemically by metabolic acidosis, elevated serum pyruvate concentration, hyperalaninemia and hyperalaninuria. There have been no further descriptions in the literature since 1973.
Mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies (ORPHA:2443)
A group of clinically heterogeneous diseases, commonly defined by lack of cellular energy due to defects of oxidative phosphorylation (OXPHOS), resulting from pathogenic mutations in the nuclear DNA. Mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies includes diseases classified according to defects in: genes encoding structural components of OXPHOS complexes (such as Leigh syndrome, coenzyme Q10 deficiency); genes encoding assembly factors of OXPHOS complexes (such as GRACILE syndrome); genes altering the stability of mitochondrial DNA (such as autosomal dominant progressive external ophthalmoplegia, mitochondrial DNA depletion syndrome); mitochondrial protein synthesis.
Mitochondrial pyruvate carrier deficiency (ORPHA:447784)
A rare pyruvate metabolism disorder characterized by neonatal onset of a mitochondrial encephalopathy with global developmental delay and the biochemical characteristics of lactic acidosis and increased serum pyruvate with normal lactate/pyruvate ratio. Additional reported manifestations include epilepsy, peripheral neuropathy, hypotonia, nystagmus, extensor plantar responses, hepatomegaly, and craniofacial dysmorphism (such as progressive microcephaly, epicanthus, long philtrum, and thin upper lip).
Mitral atresia (ORPHA:1205)
A rare congenital non-syndromic heart malformation characterized by an imperforate or absent mitral valve. In most cases, there is a univentricular atrioventricular connection to a dominant right ventricle via a tricuspid valve, and a hypoplastic left ventricle. Morphologic heterogeneity is considerable, and hemodynamic picture and clinical manifestation depend on the type and severity of associated cardiovascular anomalies (such as ventricular septal defect or aortic atresia).
Mitral valve agenesis (ORPHA:99062)
Mitral valve agenesis is a rare congenital heart malformation defined as an agenesis or severe hypoplasia of both mitral valve leaflets (complete agenesis) or one of the leaflets (partial agenesis). Complete mitral valve agenesis presents in the neonatal period with symptoms of severe mitral regurgitation and is rapidly fatal unless surgically treated. It is frequently associated with other heart malformations. Partial mitral valve agenesis may present at various ages, usually with symptoms of mitral regurgitation.
Mixed autoinflammatory and autoimmune syndrome (ORPHA:324933)
A group of systemic diseases characterized by mixed patterns of dysregulated innate and/or adaptive immune responses, leading to chronic activation of the immune system and tissue inflammation, which presents clincally with a wide range of variable, concomitant, autoimmune and autoinflammatory manifestations in various organ systems.
Mixed connective tissue disease (ORPHA:809)
Mixed connective tissue disease (MCTD) is a rare connective tissue disorder combining clinical features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM) (see these terms) and/or rheumatoid arthritis (RA).
Epidemiology
The exact prevalence of MCTD is unknown, except in Japan where it is estimated at 1/37,000. MCTD is found in all ethnic groups with a female-to-male ratio of approximately 10:1.
Clinical description
Onset usually occurs between 15 and 35 years old. Common clinical signs include Raynaud's phenomenon (see this term), arthralgia/arthritis, swollen hands/puffy fingers, sclerodactyly, and myositis. Some patients may also complain of esophageal hypomotility, lupus-like or dermatomyositis-like rashes, trigeminal neuralgia, pleuritis, pericarditis and/or pulmonary hypertension. Nonspecific constitutional symptoms such as fatigue, general malaise or low-grade fever (which should always prompt a careful search for infection) can also be observed during flares.
Etiology
The exact cause of MCTD is still unknown, but abnormal B- and T-cell immune responses against apoptotically modified self-antigens may be observed in MCTD patients.
Diagnostic methods
Most patients have high titers (often >1:1000) of anti-U1-ribonucleoprotein (RNP) and anti-U1-70 kd autoantibodies. The diagnosis of MCTD relies on overlapping features of SLE, SSc, PM, or RA (or when additional overlapping features are present in patients with a well-defined connective tissue disease) and on blood test results indicating high titers of anti-U1-RNP antibodies with normal titers of other connective tissue disease antibodies (except anti-SSA and/or anti-SSB antibodies in cases with secondary Sjögren syndrome; see this term).
Differential diagnosis
Differential diagnoses include other connective tissue diseases such as SLE, SSc, PM and/or RA, and other systemic diseases such as sarcoidosis, periarteritis nodosa, or Still's disease (see these terms).
Management and treatment
Management of MCTD is similar to that of the various overlapping connective tissue diseases. NSAIDs, antimalarials, or low-dose corticosteroids are effective for the minor or mild disease while corticosteroids (approximately 0.5-1mg/kg/day) are effective for moderate to severe disease. Higher doses of corticosteroids and additional immunosuppressants may be administered in case of severe visceral involvement. Symptomatic treatment (eg: treatment of Raynaud's phenomenon) is also of major importance.
Prognosis
MCTD is a chronic relapsing-remitting disease. The overall 10-year survival rate of the disease is approximately 80%. In general, the prognosis is favorable but it is largely dependent on which visceral manifestations of MCTD predominate. Patients with features of SSc or PM are thought to have the worst prognosis, and pulmonary hypertension has been recognized as the most frequent disease-associated cause of death.

                            Last update: 
                            October 2009


                            - Expert reviewer(s): 
                            Pr Zahir AMOURA  - Pr Laurent ARNAUD
Mixed cryoglobulinemia type II (ORPHA:93554)
A clinico-serological subtype of mixed cryoglobulinemia syndrome, an immune complex disorder, characterized by purpura, weakness and arthralgia and defined immunochemically by cryoglobulins composed of polyclonal IgGs (autoantigens) and monoclonal IgM (autoantibody).
Mixed cryoglobulinemia type III (ORPHA:93555)
A clinico-serological subtype of mixed cryoglobulinemia syndrome, is an immune complex disorder, characterized by purpura, weakness and arthralgia and defined immunochemically by cryoglobulins containing both polyclonal IgGs and polyclonal IgMs.
Mixed cystic lymphatic malformation (ORPHA:458792)
A rare common cystic lymphatic malformation characterized by a benign cystic lesion composed of dilated lymphatic channels. Mixed cystic lesions consist of cysts both larger (macrocystic) and smaller (microcystic) than 1 cm in diameter. They usually present at birth or during the first years of life and most often occur in the head and neck region but may affect any site. Symptoms depend on the location and extent of the lesion. Infection, trauma, or intracystic hemorrhage can lead to lesional expansion. Malignant transformation does not occur.
Mixed germ cell tumor (ORPHA:180234)
A rare germ cell tumor characterized by composition of two or more malignant germ cell components, the most common combination being dysgerminoma and yolk sac tumor. The tumors typically occur between childhood and young adulthood. They are usually located in the gonads, occasionally also in other regions. Clinical presentation corresponds to the individual germ cell components and the tumor location; manifestations may include abdominal pain, abdominal mass, and menstrual disorder in females, and a testicular mass in males. The most important prognostic factor is tumor stage.
Mixed neuroendocrine and non-neuroendocrine neoplasm of pancreas (ORPHA:506112)
A rare neuroendocrine neoplasm of pancreas characterized by morphologically recognizable neuroendocrine and non-neuroendocrine components, each constituting at least 30% of the tumor volume. Based on histopathology, mixed ductal- and mixed acinar-neuroendocrine carcinomas are distinguished. Patients usually present with unspecific symptoms related to tumor growth and/or metastasis, although occurrence of Zollinger-Ellison syndrome has been reported. Resectability of the tumor is the most important prognostic factor.
Mixed phenotype acute leukemia (ORPHA:530995)
A group of rare acute leukemias of ambiguous lineage characterized by the presence of separate populations of blasts of more than one lineage (bilineal), a single population of blasts coexpressing antigens of more than one lineage (biphenotypic), or a combination thereof. The diagnosis relies on immunophenotyping, the T-cell component being characterized by strong expression of cytoplasmic CD3, usually in the absence of surface CD3, the B-cell component expressing CD19, almost always together with CD10, cCD79a, CD22, or PAX5, while the most specific hallmark of the myeloid component is the presence of myeloperoxidase in the blast cytoplasm.
Mixed sclerosing bone dystrophy with extra-skeletal manifestations (ORPHA:324364)
A rare, genetic, primary bone dysplasia with increased bone density disorder characterized by bone abnormalities, including metaphyseal plaques, osteopathia striata, marked cranial sclerosis, and sclerosis of the ribs and long bones, as well as macrocephaly, cleft palate, hearing loss, developmental delay, and facial dysmorphism (hypertelorism, prominent forehead, wide nasal bridge). Hypotonia, tracheo-/laryngomalacia, and astigmatic myopia are also associated.
Mixed-type autoimmune hemolytic anemia (ORPHA:90036)
Mixed autoimmune hemolytic anemia is a type of autoimmune hemolytic anemia (AIHA; see this term) defined by the presence of both warm and cold autoantibodies, which have a deleterious effect on red blood cells at either body temperature or at lower temperatures.
Epidemiology
Mixed AIHA occurs in less than 10% of cases of AIHA, whose annual incidence is between 1/35,000-1/80,000 in North America and Western Europe.
Clinical description
Mixed AIHA can occur at any age but is rare in children. Patients with mixed AIHA usually present with abrupt onset severe hemolysis and anemia.
Etiology
Mixed AIHA can be idiopathic or secondary, mainly associated with systemic lupus erythematosus (SLE) and lymphoma.
Diagnostic methods
Diagnosis is based on clinical or laboratory evidence of hemolytic anemia and the detection of autoantibodies, usually both IgG and IgM, with the direct anti-globulin test (DAT) showing a pattern of IgG with complement C3, and the presence of cold agglutinins (IgM) in the serum at a significant titer.
Differential diagnosis
Erroneous diagnosis of mixed AIHA is sometimes made on the basis of inadequate serologic studies as a large proportion of patients with warm AIHA also have cold autoantibodies that are measured but are clinically insignificant. Unless a cold autoantibody with a high thermal amplitude (>30 degrees C) is observed in association with a warm autoantibody, a diagnosis of mixed AIHA is not warranted.
Management and treatment
The principles of management are comparable to that of warm AIHA (see this term), including corticosteroids and, if these are ineffective, splenectomy, but avoidance of cold must also be considered. Cautious transfusion is possible in cases with severe anemia. However, the best compatible or ``least incompatible'' packed red blood cell units must be identified by the blood centre to avoid post-transfusional hemolysis.
Prognosis
The disease responds to corticosteroids, and may be followed by remission, but usually runs a chronic course with intermittent exacerbations.

                            Last update: 
                            August 2010


                            - Expert reviewer(s): 
                            Pr Marc MICHEL
MME-related autosomal dominant Charcot Marie Tooth disease type 2 (ORPHA:497757)
A rare autosomal dominant hereditary axonal motor and sensory neuropathy characterized by adult onset of slowly progressive distal muscle weakness and atrophy, sensory impairment, and hyporeflexia beginning in the lower limbs. Progressive gait disturbance may lead to loss of independent ambulation in some patients at a higher age.
MMEP syndrome (ORPHA:3434)
The MMEP syndrome is a congenital syndromic form of split-hand/foot malformation (SHFM; see this term). It is characterized by microcephaly, microphthalmia, ectrodactyly of the lower limbs and prognathism. Intellectual deficit has been reported. MMEP syndrome is considered to be a very rare condition, although the exact prevalence remains unknown. The etiology is not completely understood. Disruption of the sorting nexin 3 gene (SNX3; 6q21) has been shown to play a causative role in MMEP, although this was not confirmed in recent studies.
Moderate and severe traumatic brain injury (ORPHA:90056)
A rare neurologic condition characterized by brain damage caused by an external mechanical force, with a Glasgow Coma Scale score of 9 to 12 in moderate traumatic brain injury (TBI), or 3 to 8 in severe TBI, respectively. TBI can be closed (with the dura mater remaining intact) or open (with penetration of the dura mater) and may lead to focal damage, such as cerebral contusion and hemorrhage, as well as diffuse axonal injury and secondary damage due to increased intracranial pressure. Signs and symptoms are highly variable, depending on the nature, severity, localization, and extent of the trauma.
Moderate hemophilia A (ORPHA:169805)
A moderately severe form of hemophilia A characterized by factor VIII deficiency (biological activity between 1 and 5 IU/dL) leading to abnormal bleeding as a result of minor injuries, or following trauma, surgery or tooth extraction. Spontaneous hemorrhages are rare. The condition primarily affects males but may also be observed in female carriers of disease-causing mutations.
Moderate hemophilia B (ORPHA:169796)
A moderately severe form of hemophilia B characterized by factor IX deficiency (biological activity 1-5 IU/dL) leading to abnormal bleeding as a result of minor injuries or following trauma, surgery or tooth extraction. Spontaneous hemorrhages are rare. The condition primarily affects males but may also be observed in female carriers of disease-causing mutations.
MODY (ORPHA:552)
MODY (maturity-onset diabetes of the young) is a rare, familial, clinically and genetically heterogeneous form of diabetes characterized by young age of onset (generally 10-45 years of age) with maintenance of endogenous insulin production, lack of pancreatic beta-cell autoimmunity, absence of obesity and insulin resistance and extra-pancreatic manifestations in some subtypes.
Epidemiology
MODY is the most common form of monogenic diabetes. Prevalence is estimated to be about 1/10,000 in adults and 1/23,000 in children. No specific ethnic predilection has been reported. It has been estimated that around 80% of cases are misdiagnosed as type 1 or type 2 diabetes, thus complicating prevalence and incidence estimations.
Clinical description
The clinical features of MODY vary depending on the genetic etiology. The most frequent subtypes are HNF1A-MODY (30-50%), GCK-MODY (30-50%), HNF4A-MODY (10%), and HNF1B-MODY (1-5%). The latter is also known as renal cysts and diabetes syndrome (see this term). At least 9 other genetic subtypes have been described but are very rare. Patients with HNF1A and HNF4A mutations have slowly progressing beta-cell dysfunction and respond well to treatment with low-dose sulfonylureas, which are recommended as first line therapy. Vascular complications of diabetes are observed with a similar frequency to type 1 or type 2 diabetes. Low C-Reactive Protein is seen in HNF1A-MODY and neonatal hypoglycaemia and macrosomia are reported in babies with HNF4A-MODY. GCK-MODY is characterized by asymptomatic non-progressing mild fasting hyperglycemia with low post-prandial glucose excursions from birth, is not associated with vascular complications and does not require treatment.
Etiology
Mutations in at least 13 genes have been reported to be associated with a MODY phenotype: common causes (>5% of cases): HNF1A (12q24.31), GCK (7p15.3-p15.1), HNF4A (20q13.12); rare causes (about 1% of cases): KCNJ11 (11p15.1), ABCC8 (11p15.1), INS (11p15.5), HNF1B (17q12); and very rare (described in only a few families, genetic evidence not compelling for some): CEL (9q34.3),  PDX1 (13q12.1), NEUROD1 (2q32), PAX4 (7q32.1), KLF11 (2p25) and BLK (8p23-p22).
Genetic counseling
Criteria for genetic testing for MODY include diabetes onset in adolescence or young-adulthood, maintenance of endogenous insulin production, and usually a significant family history of diabetes. Subjects will also have absence of typical features of type 1 or type 2 diabetes. Although de novo mutations can arise, cascade screening of family members is essential to ensure that those with diabetes get the correct diagnostic label and those at risk of inheriting the mutation are tested for diabetes and/or consider predictive genetic testing.

                            Last update: 
                            November 2014


                            - Expert reviewer(s): 
                            Dr Katharine OWEN
Moebius syndrome-axonal neuropathy-hypogonadotropic hypogonadism syndrome (ORPHA:2560)
A rare syndromic neurological disorder characterized by the association of Möbius syndrome (congenital facial palsy with impaired ocular abduction) with peripheral axonal neuropathy and hypogonadotropic hypogonadism. There have been no further reports since 1996.
MOGS-CDG (ORPHA:79330)
MOGS-CDG is a form of congenital disorders of N-linked glycosylation characterized by generalized hypotonia, craniofacial dysmorphism (prominent occiput, short palpebral fissures, long eyelashes, broad nose, high arched palate , retrognathia), hypoplastic genitalia, seizures, feeding difficulties, hypoventilation, severe hypogammaglobulinemia with generalized edema, and increased resistance to particular viral infections (particularly to enveloped viruses). The disease is caused by loss-of-function mutations in the gene  MOGS  (2p13.1).
MOMO syndrome (ORPHA:2563)
MOMO syndrome is a very rare genetic overgrowth/obesity syndrome (see this term) characterized by macrocephaly, obesity, mental (intellectual) disability and ocular abnormalities. Other frequent clinical signs include macrosomia, downslanting palpebral fissures, hypertelorism, broad nasal root, high and broad forehead and delay in bone maturation, in association with normal thyroid function and karyotype.
Monilethrix (ORPHA:573)
A rare genodermatosis characterized by a hair shaft dysplasia resulting in hypotrichosis.
Epidemiology
The prevalence and incidence are not known.
Clinical description
Monilethrix has an early onset in infancy. Alopecia, associated with follicular hyperkeratosis and perifollicular erythema, can involve only the occiput and the nape of the neck or, in severe forms, the entire scalp, the eyebrows and eyelashes, and secondary hair. Infants show a characteristic hair shaft dysplasia: dystrophic constrictions regularly separated by elliptical nodes of normal thickness, giving a beaded appearance of affected hair. The thin internodal region shows a high propensity to break. In some cases, nail dystrophy (koilonychia) on fingers and toes has been reported. This symptomatic triad (moniliform hair, follicular hyperkeratosis and nail dystrophy), when associated with other ectodermal defects, such as as neurological, dental, and ophthalmological alterations, constitute the ''moniliform hair syndrome''.
Etiology
Four genes have been associated with monilethrix: KRT81, KRT83 and KRT86, coding for the type II hair keratins Hb1, Hb3 and Hb6, and are responsible for the autosomal dominant form of the disease. An autosomal recessive form has also been described in a few families, caused by mutations in the DSG4 gene, coding for the desmoglein 4 protein, also involved in hypotrichosis simplex (see this term) that has clinical overlap with monilethrix.
Diagnostic methods
A trichogram shows the characteristic moniliform hairs. Trichoscopy is another approach to detect the characteristic hair shaft dysplasia of monilethrix. An electron microscopy-based diagnostic test is available.
Differential diagnosis
Differential diagnosis includes pseudomonilethrix that presents with diffuse alopecia or alopecia limited to the occipital area. However, using trichogram analysis, pseudomoniletrix hair does not present with dystrophic constrictions but with flattened irregular beading.
Genetic counseling
In severe forms with alopecia and hyperkeratosis on the body, genetic counseling would be necessary.
Management and treatment
Treatment is disappointing. The best measure is to avoid the mechanical action of combing and brushing. Depilation only achieves repopulation with normal looking hair for a short while. Temporary improvement has been described with daily doses of 125 mg of griseofulvin, zinc-sulfate, X-ray depilation, and topical application of retinoid acid. There have also been improvements with the application of minoxidil and tretinoin, and with the administration of 0.5-1 mg/kg/day of etretinate.
Prognosis
The course of the localized form of monilethrix can be favorable with a reduction of hypotrichosis with time. In general, hypotrichosis improves with age, although remissions have been noted during puberty or pregnancy.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Pr Francisco CAMACHO-MARTÍNEZ
Monoamine oxidase A deficiency (ORPHA:3057)
Monoamine oxidase-A deficiency is a very rare recessive X-linked biogenic amine metabolism disorder characterized clinically by mild intellectual deficit, impulsive aggressiveness, and sometimes violent behavior and presenting from childhood.