TaoMedAI/RareMedData huggingface dataset:
Mu-heavy chain disease (ORPHA:100024)
A type of HCD characterized by the production of incomplete monoclonal mu-heavy chains without associated light chains. The clinical presentation resembles that of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Epidemiology
The prevalence is unknown but the disease is extremely rare. Only about 35 cases have been reported in the world literature.
Clinical description
The age at diagnosis is usually between 50 and 60 years. The most common presenting symptoms are those of a lymphoproliferative malignancy although peripheral lymphadenopathy is less common than in CLL. Lytic bone lesions and osteoporosis have been reported in a few cases.
Etiology
The cause of mu-HCD is unknown.
Diagnostic methods
The diagnosis of mu-HCD is made by documentation of the abnormal heavy chain by immunofixation of serum and urine. Unlike alpha- and gamma-HCD, some patients with mu-HCD have increased free light chain secretion (Bence Jones proteinuria). Examination of the bone-marrow shows an increase in lymphocytes, plasma cells, or plasmacytoid lymphocytes.
Differential diagnosis
The differential diagnosis of mu-HCD includes all lymphoplasma-cell proliferative disorders. Without a suspicion for the disease, mu-HCD is difficult to diagnose. The finding of Bence Jones proteinuria in a patient with a lymphoproliferative disorder and vacuolated plasma cells in the bone marrow deserves further investigation for possible mu-HCD.
Management and treatment
There is no specific treatment for mu-HCD. If mu-HCD protein is found in the serum of an asymptomatic patient this should be followed closely for the development of a symptomatic lymphoplasma-cell proliferative disorder. Treatment of symptomatic patients with mu-HCD is similar to that employed in patients with CLL (eg, glucocorticoids, alkylating agents).
Prognosis
The disease course and prognosis seen in mu-HCD is highly variable. The median survival from time of diagnosis is 24 months and ranges from < 1 month to 11 years.

                            Last update: 
                            October 2011


                            - Expert reviewer(s): 
                            Pr Robert KYLE  - Dr Dietlind WAHNER-ROEDLER
Mucinous adenocarcinoma of ovary (ORPHA:398961)
Mucinous adenocarcinoma of ovary is a rare, malignant epithelial tumor of the ovary characterized, macroscopically, by a large, usually unilateral tumor with smooth surface and evenly distributed cystic and solid areas and, histologically, by a complex papillary growth pattern with microscopic cystic glands and necrotic debris. Patients often present with pelvic pain and pressure, abdominal mass or gastrointestinal problems such as early satiety or bloating.
Mucinous adenocarcinoma of the appendix (ORPHA:391723)
Mucinous adenocarcinoma of the appendix is a very rare, slow growing, well-differentiated epithelial neoplasm of the appendix characterized by abundant mucin production. Clinically, it presents as acute appendicitis (with abdominal pain, fever, leukocytosis) or as pseudomyxoma peritonei (wide-spread presence of mucin within the peritoneal cavity), however some patients may be completely asymptomatic at the time of diagnosis. In many cases, a second gastrointestinal malignancy is present.
Mucinous cystadenocarcinoma of the pancreas (ORPHA:424053)
A rare, epithelial tumor of the pancreas characterized, histologically, by columnar, mucin-producing epithelium associated with ovarian-type subepithelial stroma, which does not communicate with the pancreatic ductal system, most frequently localized to the body or tail of the pancreas. Clinically, small tumors (<3 cm) are usually asymptomatic, while large tumors typically present obstructive jaundice, a palpable abdominal mass, and may associate portal hypertension, hemobilia and diabetes mellitus.
Mucinous tubular and spindle cell renal carcinoma (ORPHA:319322)
Mucinous tubular and spindle cell renal carcinoma is a rare subtype of renal cell carcinoma characterized, histologically, by tubular architecture and sheets of spindle cells embedded in a mucinous/myxoid stroma and, macroscopically, by a solid, generally well-circumscribed, partially encapsulated tumor of variable size, with a homogenously colored, bulging cut surface, occassionally containing areas of hemorrhage or necrosis, usually located in the cortex. Patients can present abdominal/flank pain, adbominal mass and/or hematuria, however most are asymptomatic and tumor is discovered incidentally. Indolent behavior is frequent and association with nephrolithiasis and end-stage kidney disease has been noted.
Mucolipidosis type III gamma (ORPHA:423470)
Mucolipidosis type III gamma (ML 3 gamma) is a very rare lysosomal disease, that has most often been observed in the Middle East, characterized by a progressive slowing of the growth rate in early childhood; stiffness and pain in shoulders, hips, and finger joints; a gradual, mild coarsening of facial features; and by a slower progression, milder clinical course and longer life expectancy than that seen in mucolipidosis type II and mucolipidosis type III alpha/beta. Cognitive function is normal or only slightly impaired and retinitis pigmentosa has been reported in a few patients. Many survive into early adulthood, but ultimately succumb to cardiorespiratory insufficiency.
Mucopolysaccharidosis type 2, severe form (ORPHA:217085)
Mucopolysaccharidosis type 2 (MPS2, see this term), severe form (MPS2S), is associated with a massive accumulation of glycosaminoglycans and a wide variety of symptoms including a rapidly progressive cognitive decline; it is most often fatal in the second or third decade.
Epidemiology
Prevalence of MPS2 at birth in Europe is 1/166,000, the severe form accounts for at least two-thirds of all cases.
Clinical description
MPS2S presents with the spectrum of symptoms observed in all MSP2 (see this term) cases, often with an earlier presentation. MPS2S patients have a decrease in growth rate in early to mid-childhood, along with respiratory difficulties and a thickening of lips and nostrils as well as an enlarged and protruding tongue (distinctive facies), which may become evident between 2-4 years of age. Psychomotor milestones are delayed, and regression often occurs. Between the ages of 2-6 years patients begin to exhibit aggressive behavior and hyperactivity, often lacking any sense of danger as they follow a course of progressive cognitive decline. Vision may be affected, and progressive hearing loss occurs in most cases. Myocardial thickening and cardiac valve dysfunction are common. Approximately 60-80 % of patients with MPS2 have the severe form of the disease with neurological implications.
Etiology
MPS2 results from iduronate-2-sulfatase (I2S) deficiency, which leads to lysosomal accumulation of two specific mucopolysaccharides, dermatan sulfate and heparan sulfate. MPS2S appears to be associated with a complete absence of functional enzyme due to nonsense mutations or complete gene deletions or rearrangements. In most cases, however, prognosis cannot be established by genotype alone.
Diagnostic methods
Diagnosis is based on detection of increased levels of DS and HS in the urine and confirmed by the demonstration of the enzyme deficiency in the serum, leukocytes or fibroblasts, or in dried blood spot samples. Enzymatic activity of another sulfatase should also be assessed. Genetic testing is possible; sequencing must include the entire IDS gene including its promoter region.
Management and treatment
Regular evaluation of patients should be followed by palliative care as is necessary. Cranial shunting to relieve hydrocephalus is often required. Weekly intravenous infusion with recombinant enzyme preparations has been shown to help with somatic symptoms. Intrathecal administration of enzyme replacement therapy holds promise to treat neurological aspects of MSP2; testing of such treatments is ongoing.
Prognosis
Prognosis is poor. MPS2S is most often fatal within the second or third decade of life, due to obstructive airway disease, infection, or cardiac failure due to valve dysfunction, pulmonary hypertension or cardiomyopathy.

                            Last update: 
                            September 2013


                            - Expert reviewer(s): 
                            Dr Barbara BURTON
Mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders (ORPHA:505248)
A rare genetic disease characterized by early-onset respiratory difficulties and frequent respiratory infections, congenital heart defects, dysostosis multiplex, hepatosplenomegaly, renal involvement, hematopoietic abnormalities, facial dysmorphism (coarse facial features, large forehead, synophrys, long eyelashes, broad nasal bridge, macroglossia, short neck, and low hairline), and global developmental delay. Laboratory examination shows increased urinary excretion of glycosaminoglycans and increased plasma heparan sulfate, but no lysosomal enzyme deficiency. The disease is usually fatal in the first years of life.
Mueller-Weiss syndrome (ORPHA:566943)
A rare bone disease characterized by spontaneous adult-onset tarsal navicular osteonecrosis. Patients present with chronic mid- and hindfoot pain, swelling and tenderness over the dorsomedial aspect of the midfoot, flattening of the medial longitudinal arch, and pes planovarus. Radiographic findings include comma-shaped deformity due to collapse of the lateral part of the navicular bone and medial or dorsal protrusion of a portion or the entire bone. The condition may be bilateral or asymmetric and associated with pathological fractures.
Multicentric carpo-tarsal osteolysis with or without nephropathy (ORPHA:2774)
A very rare syndrome characterized by progressive loss of bone, usually the capsal and tarsal bones, resulting in deformity and disability, as well as chronic renal failure in many cases. The bone and renal disorders are sometimes associated with intellectual deficit and facial abnormalities.
Multicentric reticulohistiocytosis (ORPHA:139436)
A rare non-Langerhans cell histiocytosis characterized by the association of specific nodular skin lesions and destructive arthritis.
Epidemiology
Prevalence is unknown but around 200 cases have been reported in the literature so far.
Clinical description
Onset is insidious, usually occurring at around 50 years of age. Multicentric reticulohistiocytosis (MRH) is a progressive disease, articular inflammation becomes more severe and, after periods of worsening and improving symptoms, incapacitating arthritis is a frequent feature. Multiple joints may be involved (mainly of the hands, wrists, shoulders, knees, hips and ankles). Joint symptoms oscillate and severe deforming arthritis, known as mutilating arthritis, is a prominent manifestation in between 11 and 45% of the cases, depending on the patient series. Similarly, cutaneous nodules appear and regress, with new eruptions developing over periods of many months, as the old ones become inactive, stabilize or disappear. The cutaneous nodules are either skin-colored or have a red/brown appearance and are usually asymptomatic. They are more frequent on the upper body, particularly the hands, and may also appear on mucosal surfaces. Internal organ involvement has also been reported. After a period of many years (usually 6 to 8), in the majority of cases, arthritis becomes quiescent and the mucocutaneous nodules stabilize or become smaller.
Etiology
The etiology is unknown. MRH is believed to reflect a peculiar type of reactive inflammatory response to unknown stimuli with involvement of macrophages and T lymphocytes. An underlying malignancy has been described in around a quarter of patients.
Diagnostic methods
Histopathological and immunohistochemical studies (revealing the characteristic reticulohistiocytic granulomas mainly composed of CD68 positive cells) are diagnostic in most cases. Radiologic examinations should be performed in all patients.
Differential diagnosis
The differential diagnosis should include leprosy, rheumatoid arthritis, xanthogranulomas, lymphomas, sarcoidosis, Urbach-Wiethe disease, Farber disease and dermatomyositis (see these terms).
Management and treatment
At present, no satisfactory treatment is available. Some chemotherapeutical schemes, particularly those involving alkylating agents and specific therapies targeted towards the tumor necrosis factor (TNF) or its receptors may lead to some improvement. Systemic steroids are usually of only limited benefit.
Prognosis
Patients with MRH usually undergo spontaneous remission within a variable period of 6 to 8 years, however, sequelae (esthetic sequelae associated with the skin lesions and deforming sequelae associated with the arthritis) are frequent after cure. Death can occur due to internal organ involvement or as a result of the underlying malignancy.

                            Last update: 
                            February 2009


                            - Expert reviewer(s): 
                            Dr Flavio LUZ  - Pr Marcia RAMOS-E-SILVA
Multicystic dysplastic kidney (ORPHA:1851)
A rare congenital anomaly of the kidney and urinary tract (CAKUT) in which one or both kidneys (unilateral or bilateral MCDK respectively) are large, distended by multiple cysts, and non-functional. Unilateral MCDK is typically asymptomatic if the other kidney is fully functional but may occasionally present with abdominal obstructive signs when the cysts become too large. Bilateral MCDK is considered a lethal entity and neonates present with features of the Potter sequence, severe pulmonary hypoplasia and severe renal failure, and generally die shortly after birth.
Multifocal atrial tachycardia (ORPHA:3282)
Multifocal atrial tachycardia is a rare supraventricular arrhythmia in neonates and young infants that is characterized by multiple P waves with varying P wave morphology and is usually asymptomatic.
Epidemiology
It is a very rare condition occurring in around 1 per 150,000 live births.
Clinical description
'The disease mainly affects newborn infants (or those younger than 6 months of age) with a normal heart and no other underlying illness. Most infants are asymptomatic but some may show shortness of breath or respiratory distress. Less often, the disorder may occur in children with heart malformations (such as hypertrophic cardiomyopathy, tetralogy of Fallot, or atrioventricular canal defect; see these terms) or in those having recently undergone an open-heart surgery. Very rarely, multifocal atrial tachycardia can be associated with other clinical features and be part of a syndrome, such as in Costello syndrome where it is associated with growth retardation, coarse facies, intellectual disability, and skin anomalies (see this term).'
Etiology
The etiology is unknown.
Diagnostic methods
Diagnosis is made by surface electrocardiogram: atrial activity is polymorphic (at least 3 different morphologies of P waves with a discrete isoelectric baseline, and variable PP, RR, and PR intervals), rapid (atrial rates can increase up to 400 beats per minute), and irregular. Atrioventricular conduction is variable so that some P waves are not conducted. Rate-related QRS widening (aberrancy) is sometimes seen.
Differential diagnosis
Differential diagnosis includes most other types of tachycardia (e.g. nonsustained ventricular tachycardia, paroxysmal supraventricular tachycardia (PSVT)).
Management and treatment
If the ventricular rate is relatively normal and the infant is asymptomatic with normal heart function, no treatment may be necessary. Cardioversion is unsuccessful due to the fact that the arrhythmia is restarting all the time. A beta-blocker is probably the drug of choice, with an occasional patient with poor ventricular function needing treatment with amiodarone.
Prognosis
The natural history of multifocal atrial tachycardia is spontaneous resolution within weeks or months. In those who require drug treatment, medication can be withdrawn after that time. The long term outlook is good, with no late recurrence.

                            Last update: 
                            November 2013


                            - Expert reviewer(s): 
                            Dr Christopher WREN
Multifocal infantile hemangioma with extracutenous involvement (ORPHA:2123)
Diffuse neonatal hemangiomatosis is a rare vascular tumor from unknown origin characterized by multiple, progressive, rapidly growing cutaneous hemangiomas (e.g. in the scalp, face, trunk and extremities) associated with widespread visceral hemangiomas in the liver, lungs, gastrointestinal tract, brain, and meninges.
Multifocal lymphangioendotheliomatosis-thrombocytopenia syndrome (ORPHA:464321)
A rare lymphatic system anomaly characterized by multifocal congenital and progressive vascular lesions of the skin, gastrointestinal tract, and occasionally other anatomic sites, causing potentially life-threatening thrombocytopenic coagulopathy. Macroscopically, the lesions appear as round to oval, red-brown plaques, as large as a few centimeters in diameter. Histopathologically, they consist of dilated, thin-walled vessels with variable endothelial hyperplasia, positive for lymphatic endothelial cell markers, and resembling benign lymphangioendothelioma.
Multifocal motor neuropathy (ORPHA:641)
Multifocal motor neuropathy (MMN) is a rare acquired immune-mediatedneuropathy characterized clinically by a purely motor deficit with conduction block and asymmetric multifocal weakness, fasciculations, and cramping.
Multifocal pattern dystrophy simulating fundus flavimaculatus (ORPHA:99003)
A rare, patterned dystrophy of the retinal pigment epithelium characterized by multiple yellowish irregular flecks scattered or interconnected around the macula, simulating what is observed in Stargardt disease, and usually asymptomatic until adulthood when patients present with a slowly progressive loss of vision that often only becomes apparent in old age.
Multilocular cystic renal neoplasm of low malignant potential (ORPHA:319287)
Multilocular cystic renal neoplasm of low malignant potential is a rare subtype of clear cell renal cell carcinoma with distinct pathological features of cysts lined by occasionally flattened cuboidal clear cells and septa containing aggregates of epithelial cells with clear cytoplasm, and excellent prognosis. The tumor usually presents as an asymptomatic, unilateral, solitary lesion, macroscopically consisting of numerous, fluid-filled, septated cysts of variable size. Rarely, the symptoms typically associated with renal tumors (flank pain, hematuria, palpable mass) may be present.
Multiloculated renal cyst (ORPHA:97366)
A rare benign renal tumor characterized by a typically unilateral, solitary, multiloculated cystic mass consisting of small, non-communicating cysts with flat, cuboidal, or hobnail epithelial lining, separated by fibrous septa which may have an ovarian stroma-like appearance or be paucicellular. The tumor is surrounded by a thick fibrous capsule and does not contain solid areas or necrosis. Patients may be asymptomatic or present with a palpable abdominal mass and/or abdominal or flank pain. Age distribution is bimodal, the typical age of onset being either below five or between 40 and 70 years of age.
Multiminicore myopathy (ORPHA:598)
A rare hereditary neuromuscular disorder characterized by multiple cores on muscle biopsy and clinical features of a congenital myopathy.
Epidemiology
Prevalence is unknown.
Clinical description
Marked clinical variability corresponds to genetic heterogeneity: the most instantly recognizable classic phenotype characterized by spinal rigidity, early scoliosis and respiratory impairment is due to recessive mutations in the selenoprotein N (SEPN1) gene, whereas recessive mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been associated with a wider range of clinical features comprising external ophthalmoplegia, distal weakness and wasting or predominant hip girdle involvement resembling central core disease (CCD). In the latter forms, there may also be a histopathologic continuum with CCD caused by dominant RYR1 mutations, reflecting the common genetic background.
Etiology
The pathogenetic mechanisms of RYR1-related MmD are currently not well understood, but are likely to involve altered excitability and/or changes in calcium homeostasis. The presence of calcium-binding motifs within the selenoprotein N protein also suggests a possible role in calcium handling.
Diagnostic methods
The diagnosis of MmD is based on the presence of suggestive clinical features and multiple cores on muscle biopsy. Muscle MRI may aid genetic testing as distinct patterns of selective muscle involvement can be detected depending on the genetic background. Mutational analysis of the RYR1 or the SEPN1 gene may provide genetic confirmation of the diagnosis.
Management and treatment
Management is mainly supportive and has to address the risk of marked respiratory impairment in SEPN1-related MmD and the possibility of susceptibility to malignant hyperthermia in RYR1-related forms.
Prognosis
In the majority of patients, weakness is static or only slowly progressive, with the degree of respiratory impairment being the most important prognostic factor.

                            Last update: 
                            July 2007


                            - Expert reviewer(s): 
                            Dr Heinz JUNGBLUTH
Multinodular goiter-cystic kidney-polydactyly syndrome (ORPHA:2091)
Multinodular goiter - cystic kidney - polydactyly syndrome is a very rare syndrome characterized by the association of multinodular goiter, cystic renal disease and digital anomalies.
Epidemiology
It has been described in two sibs and one unrelated child.
Clinical description
The two sibs had digitalized thumbs and preaxial polydactyly, the third child had normal thumbs and postaxial polydactyly. Goiter and/or digitalized thumbs and/or polydactyly were present in other members of families.
Genetic counseling
This syndrome seems to be transmitted as an autosomal dominant trait with variable expression and incomplete penetrance.

                            Last update: 
                            October 2010
Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (ORPHA:500135)
A rare genetic lethal multiple congenital anomalies/dysmorphic syndrome characterized by severe hydranencephaly and renal dysplasia or agenesis. Pregnancy is complicated by oligo- or anhydramnios, leading to features of Potter sequence (including typical facies and microretrognathia, limb contractures, talipes equinovarus, and pulmonary hypoplasia) in the fetus. Affected fetuses either die in utero or shortly after birth. Histology of the brain shows widespread presence of multinucleated neurons and glial cells.
Multiple benign circumferential skin creases on limbs (ORPHA:2505)
A rare genetic disease characterized by benign circumferential skin creases, mainly on the limbs, due to folding of excess skin. The creases often improve spontaneously in childhood. Patients also exhibit variable degrees of intellectual disability, short stature, cleft palate, and facial dysmorphism (including epicanthal folds, microphthalmia, broad nasal bridge, low-set, posteriorly rotated ears, and microstomia, among others). Variable additional features have been reported, such as seizures, infantile hypotonia, hearing impairment, strabismus, and urogenital anomalies. Brain imaging may show hypoplastic corpus callosum or mildly dilated ventricles.
Multiple carboxylase deficiency (ORPHA:148)
A group of inborn errors of biotin metabolism characterized by reduced activities of biotin-dependent enzymes resulting in a wide spectrum of symptoms, including feeding difficulty, breathing difficulties, lethargy, seizures, skin rash, alopecia, and developmental delay. This group includes biotinidase deficiency and biotin holocarboxylase synthetase deficiency.