TaoMedAI/RareMedData huggingface dataset:
Methylmalonic acidemia without homocystinuria (ORPHA:293355)
Methylmalonic acidemia is an inborn error of vitamin B12 metabolism characterized by gastrointestinal and neurometabolic manifestations resulting from decreased function of the mitochondrial enzyme methylmalonyl-CoA mutase.
Epidemiology
Prevalence of methylmalonic acidemia has been estimated at 1/48,000 to 1/61,000 in North America, and at 1/26,000 in China (these values may include patients with methylmalonic acidemia with homocystinuria; see this term).
Clinical description
Clinical signs include lethargy, failure to thrive, recurrent vomiting, dehydration, respiratory distress, and muscle hypotonia, as well as developmental delay, intellectual deficit, hepatomegaly and coma. Long-term consequences of the disorder include neurological damage due to metabolic stroke affecting the brain stem, and end stage renal failure. The disease can either be responsive or unresponsive to treatment with vitamin B12 (vitamin B12-responsive or unresponsive methylmalonic acidemia; see these terms). Patients with mut0 or cblB tend to be more severely affected than patients with cblA, cblDv2 or mut-.
Etiology
Vitamin B12-responsive methylmalonic acidemia is caused by defects in the synthesis of adenosylcobalamin (AdoCbl) that result from genetic defects in cobalamin metabolism (cblA, cblB or cblD variant 2 [cblDv2]). Vitamin B12-unresponsive methylmalonic acidemia is caused by complete (mut0) or partial (mut-) deficiency in the activity of the mitochondrial enzyme methylmalonyl-CoA mutase. cblA is caused by mutations in the MMAA gene (4q31.1-2), cblB by mutations in the MMAB gene (12q24.1), cblDv2 by mutations in the MMADHC gene (2q23.2), and mut0 and mut- by mutations in the MUT gene (6p21), and all are transmitted in an autosomal recessive manner. The previously reported cblH disorder is now known to be cblDv2.

                            Last update: 
                            March 2012


                            - Expert reviewer(s): 
                            Dr David ROSENBLATT  - Dr David WATKINS
Methylmalonic aciduria due to transcobalamin receptor defect (ORPHA:280183)
Methylmalonic aciduria due to transcobalamin receptor defect is a rare metabolite absorption and transport disorder characterized by a moderate increase of methylmalonic acid (MMA) in the blood and urine due to decreased cellular uptake of cobalamin resulting from decreased transcobalamin receptor function. Patients are usually asymptomatic however, screening reveals increased C3-acylcarnitine and MMA in plasma. Serum homocysteine levels may vary from normal to moderately elevated and retinal vascular occlusive disease, resulting in severe visual loss, has been reported.
Mevalonate kinase deficiency (ORPHA:309025)
A rare inborn error of metabolism characterized by a spectrum of presentation ranging from hyperimmunoglobulinemia D with periodic fever (HIDS) to mevalonic aciduria.
Epidemiology
Some 300 cases of mevalonate kinase deficiency (MKD) have been reported worldwide. Many cases are probably not diagnosed, implying that prevalence may be higher than expected. Males and females are affected equally.
Clinical description
All patients suffer from recurrent inflammatory episodes with fever, pain, diarrhea, skin eruptions, and headache. Patients with the more severe phenotype, mevalonic aciduria (MVA), can also exhibit developmental, neurological and ophthalmological involvement. MKD develops antenatally, during infancy, or in childhood and covers a clinical spectrum ranging from a relatively mild periodic fever disorder to a lethal metabolic disease. There are two types of MKD depending on the severity of the clinical manifestations: Hyperimmunoglobinemia D syndrome (HIDS) with periodic episodes of fever lasting 3 to 7 days, and MVA which includes dysmorphic features, failure to thrive, developmental delay, progressive ataxia, psychomotor delay, progressive ocular manifestations, short stature, and myopathy later in life.
Etiology
MKD is caused by mutations in the MVK gene (12q24), which encodes mevalonate kinase involved in cholesterol and isoprenoid production. The exact pathogenesis is currently unclear. Enzyme deficiency results in impaired cholesterol biosynthesis and increased production of inflammatory mediators. The residual enzyme activity is correlated with the severity of the manifestations with HIDS patients having a residual activity between 1.8% and 28%, while MVA patients have enzyme activities below 0.5%. However, overlap between both phenotypes may occur. No clear genotype-phenotype correlations have been identified.
Genetic counseling
MKD follows an autosomal recessive pattern of inheritance.

                            Last update: 
                            February 2016


                            - Expert reviewer(s): 
                            Dr Joost FRENKEL  - Dr Jerold JEYARATNAM
Mevalonic aciduria (ORPHA:29)
A rare, severe form of mevalonate kinase deficiency (MKD) characterized by dysmorphic features, failure to thrive, psychomotor delay, ocular involvement, hypotonia, progressive ataxia, myopathy, and recurrent inflammatory episodes.
Epidemiology
The exact prevalence and incidence of MVA are not known. Fewer than 50 patients have been reported to date. A small proportion of patients with MKD have mevalonic aciduria (MVA), while most cases correspond to the milder phenotype known as Hyperimmunoglobinemia D with periodic fever (HIDS).
Clinical description
Onset of MVA is usually during infancy and in some severe cases antenatally. The clinical presentation is variable with cases of severe disease with significantly reduced life expectancy to milder cases with no effect on life expectancy. Infants may be born with shortened limbs and dysmorphic features (dolichocephaly, microcephaly, frontal bossing, a triangular-shaped face, down-slanting eyelids, and dysplastic or low-set ears. Affected patients may also present with marked failure to thrive, and recurrent episodes of fever (that may be fatal in infancy) possibly accompanied by hepatosplenomegaly, lymphadenopathy, abdominal pain, vomiting, diarrhea, arthralgia, myalgia, mouth ulcers, and skin eruptions. During childhood, patients may show failure to thrive, developmental delay and progressive ataxia; in later childhood or adolescence they may develop progressive ocular disorders such as uveitis, blue sclera, retinitis pigmentosa, or cataracts. Short stature and myopathy are reported in older patients.
Etiology
MVA is caused by mutations in the MVK gene (12q24). MVK encodes mevalonate kinase, which is involved in cholesterol and isoprenoid production. In patients with the severe form of MKD, enzyme deficiency is nearly complete causing the severe manifestations of the disorder. Severity usually depends on the degree of residual enzyme activity.
Genetic counseling
MKD follows an autosomal recessive pattern of inheritance. Genetic counseling should be proposed to affected families.
Management and treatment
Inflammatory attacks can often be controlled with interleukin-1 blocking agents such as canakinumab or anakinra. Severely affected patients have been seen to improve significantly upon allogeneic hematopoietic stem cell transplantation.

                            Last update: 
                            February 2016


                            - Expert reviewer(s): 
                            Dr Joost FRENKEL  - Dr Jerold JEYARATNAM
MGAT2-CDG (ORPHA:79329)
A rare form of disorder of protein N-glycosylation characterized by facial dysmorphism (large, posteriorly rotated ears with prominent antihelices, convex nasal ridge, open mouth, large and crowded teeth), stereotypic hand movements, seizures, and varying degrees of developmental delay. A bleeding tendency is also observed and this results from diminished platelet aggregation. The disease is caused by loss-of-function mutations in the gene MGAT2 (14q21).
Micro syndrome (ORPHA:2510)
Micro syndrome is an autosomal recessive disorder caracterised by ocular and neurodevelopmental defects and by microgenitalia. It presents with severe intellectual disability, microcephaly, congenital cataract, microcornea, microphthalmia, agenesis/hypoplasia of the corpus callosum, and hypogenitalism.
Epidemiology
Since its initial description, 26 cases of Micro syndrome have been reported in the literature.
Clinical description
With exception of the ophthalmologic features, the clinical and dysmorphic findings are either unapparent or subtle in the early postnatal period.
Etiology
Mutations in RAB3GAP, a gene showing linkage to a region of homozygosity at 2q21.3, have been identified in some families. The RAB3GAP gene encodes a member of the Rab3 protein family, which is involved in regulated exocytosis of neurotransmitters and hormones. It has been suggested that the hypogenitalism is hypothalamic in origin, and that the ocular and neurodevelopmental defects result from abnormal neurotransmitter vesicular transport and exocytosis.
Diagnostic methods
Ocular findings are the most reliable diagnostic signs of Micro syndrome, especially during infancy. Pathognomonic ophthalmologic findings include microphthalmia, microcornea, cataract, atonic pupils, mild optic atrophy, and severe cortical vision impairment.
Differential diagnosis
Micro syndrome should be considered in any infant with congenital cataract.
Management and treatment
There is no specific treatment for Micro syndrome and the management is symptomatic. The conventional approach used for congenital cataract should be recommended.

                            Last update: 
                            January 2006


                            - Expert reviewer(s): 
                            Dr Pinar AGRAS  - Dr Murat DERBENT
Microbrachycephaly-ptosis-cleft lip syndrome (ORPHA:2511)
Microbrachycephaly-ptosis-cleft lip syndrome is characterised by the association of intellectual deficit, microbrachycephaly, hypotelorism, palpebral ptosis, a thin/long face, cleft lip, and anomalies of the lumbar vertebra, sacrum and pelvis. It has been described in two Brazilian sisters. Transmission appears to be autosomal recessive.
Microcephalic osteodysplastic dysplasia, Saul-Wilson type (ORPHA:85172)
Microcephalic osteodysplastic dysplasia, Saul-Wilson type is a skeletal dysplasia characterized by a distinct facial phenotype, short stature, brachydactyly, clubfoot deformities, cataracts, and microcephaly. It has been described in four patients. Facial features include frontal bossing with a depression over the metopic suture, a narrow nasal root with a beaked nose, and midfacial hypoplasia with prominent eyes. Characteristic radiographic findings are observed (irregularities of the vertebral bodies, hypoplasia of the odontoid process, short phalanges, coning several epiphyses etc.).
Microcephalic primordial dwarfism due to ZNF335 deficiency (ORPHA:329228)
Microcephalic primordial dwarfism due to ZNF335 deficiency is characterized by severe antenatal microencephaly, simplified gyration, agenesis of the corpus callosum, absence of basal ganglia (very rare), pontocerebellar atrophy and involvement of the white matter with secondary cerebral atrophy. Congenital cataract, choanal atresia, multiple arthrogryposis and spastic tetraparesis can occur.
Microcephalic primordial dwarfism, Dauber type (ORPHA:319675)
Microcephalic primordial dwarfism, Dauber type is a rare, genetic developmental defect during embryogenesis characterized by severe pre- and postnatal growth retardation, severe microcephaly, severe developmental delay and intelletual disability, severe adult short stature and facial dysmorphism (incl. hypotelorism, small ears, prominent nose). Other reported features include skeletal anomalies (Madelung deformity, clinodactyly, mild lumbar scoliosis, bilateral hip dysplasia) and seizures. Absence of thelarche and menarche is also associated.
Microcephalic primordial dwarfism, Montreal type (ORPHA:2617)
A rare, genetic multiple congenital anomalies/dysmorphic syndrome characterized by severe short stature and craniofacial dysmorphism (microcephaly, narrow face with flat cheeks, ptosis, prominent nose with a convex ridge, low-set ears with small or absent lobes, high-arched/cleft palate, micrognathia), associated with premature graying and loss of scalp hair, redundant, dry and wrinkled skin of the palms, premature senility and varying degrees of intellectual disability. Cryptorchidism and skeletal anomalies may also be observed. There have been no further descriptions in the literature since 1970.
Microcephalic primordial dwarfism, Toriello type (ORPHA:2643)
A rare disorder characterised by growth retardation with prenatal onset, cataracts, microcephaly, intellectual deficit, immune deficiency, delayed ossification and enamel hypoplasia. It has been described in two siblings. Transmission is autosomal recessive.
Microcephalic primordial dwarfism-insulin resistance syndrome (ORPHA:436182)
A rare genetic disease characterized by severe pre- and postnatal growth failure with short stature and microcephaly, facial dysmorphism (including a small jaw and prominent midface), severe insulin resistance, fatty liver, and hypertriglyceridemia developing in childhood, and primary gonadal failure. Mild global learning difficulties and acanthosis nigricans have also been reported.
Microcephaly-albinism-digital anomalies syndrome (ORPHA:2513)
Microcephaly - albinism - digital anomalies syndrome is a very rare syndrome associating microcephaly, micrognathia, oculocutaneous albinism, hypoplasia of the distal phalanx of fingers and agenesia of the distal end of the right big toe.
Epidemiology
It has been described in two sibs.
Clinical description
Both brother and sister had psychomotor retardation and died in the course of a respiratory infection.
Genetic counseling
The reported cases suggest that the condition is hereditary, and is transmitted as an autosomal recessive trait.

                            Last update: 
                            October 2010
Microcephaly-brachydactyly-kyphoscoliosis syndrome (ORPHA:3433)
Microcephaly-brachydactyly-kyphoscoliosis syndrome is characterized by profound intellectual deficit in association with microcephaly, short stature, brachydactyly type D, a flattened occiput, downslanting palpebral fissures, low-set large ears, a broad prominent nose and kyphoscoliosis. It has been described in three sisters. The disorder is likely to be transmitted as an autosomal recessive trait.
Microcephaly-brain defect-spasticity-hypernatremia syndrome (ORPHA:2523)
Microcephaly-brain defect-spasticity-hypernatremia syndrome is a rare congenital genetic syndrome with a central nervous system malformation as a major feature characterized by microcephaly, hypertonia, developmental delay and cognitive impairment, swallowing difficulty, hypernatremia, and hypoplasia of the frontal parts and fusion of the lateral ventricles on brain MRI. There have been no further descriptions in the literature since 1986.
Microcephaly-capillary malformation syndrome (ORPHA:294016)
Microcephaly-capillary malformation syndrome is a rare, genetic vascular anomaly characterized by severe congenital microcephaly, poor somatic growth, diffuse multiple capillary malformations on the skin, intractable epilepsy, profound global developmental delay, spastic quadriparesis and hypoplastic distal phalanges.
Microcephaly-cardiac defect-lung malsegmentation syndrome (ORPHA:2516)
Microcephaly - cardiac defect - lung malsegmentation syndrome is a very rare syndrome characterized by the combination of microcephaly, heart defects, renal hypoplasia, lung segmentation defects and cleft palate.
Epidemiology
It has been described in three female sibs (including a fetus).
Clinical description
Dysmorphic features were not characteristic.
Genetic counseling
The condition seems to be hereditary, and transmitted as an autosomal recessive trait.
Prognosis
Prognosis is poor and all infants died in infancy.

                            Last update: 
                            July 2010
Microcephaly-cardiomyopathy syndrome (ORPHA:2515)
Microcephaly-cardiomyopathy syndrome is characterised by severe intellectual deficit, microcephaly and dilated cardiomyopathy. Hand and foot anomalies have also been reported. The syndrome has been described in three individuals. Transmission is autosomal recessive.
Microcephaly-cerebellar hypoplasia-cardiac conduction defect syndrome (ORPHA:329332)
Microcephaly-cerebellar hypoplasia-cardiac conduction defect syndrome is a rare, genetic congenital anomalies/dysmorphic syndrome characterized by growth failure, global developmental delay, profound intellectual disability, autistic behaviors, acquired second-degree heart block with bradycardia and vasomotor instability. Hands and feet present with long fusiform fingers, campto-clinodactyly and crowded toes while craniofacial dysmorphism includes microcephaly, broad forehead, thin eyebrows, upslanting palpebral fissures, large ears with prominent antihelix, prominent nose, long philtrum, thin upper lip vermillion and prominent lower lip. Neurological signs include hypotonia, brisk reflexes, dystonic-like movements and truncal ataxia and imaging shows cerebellar hypoplasia and simplified gyral pattern.
Microcephaly-cervical spine fusion anomalies syndrome (ORPHA:2522)
Microcephaly-cervical spine fusion anomalies syndrome is characterized by microcephaly, facial dysmorphism (beaked nose, low-set ears, downslanting palpebral fissures, micrognathia), mild intellectual deficit, short stature, and cervical spine fusion anomalies producing spinal cord compression. It has been described in two brothers born to consanguineous parents. Transmission is likely to be autosomal recessive.
Microcephaly-cleft palate-abnormal retinal pigmentation syndrome (ORPHA:2521)
Microcephaly-cleft palate-abnormal retinal pigmentation syndrome is a rare orofacial clefting syndrome characterized by microcephaly, cleft of the secondary palate and other variable abnormalities, including abnormal retinal pigmentation, facial dysmorphism with hypotelorism and maxillary hypoplasia. Goiter, camptodactyly, abnormal dermatoglyphics and mild intellectual disability may also be associated. There have been no further descriptions in the literature since 1983.
Microcephaly-complex motor and sensory axonal neuropathy syndrome (ORPHA:423894)
Microcephaly-complex motor and sensory axonal neuropathy syndrome is an extremely rare subtype of hereditary motor and sensory neuropathy characterized by severe, rapidly-progressing, distal, symmetric polyneuropathy and microcephaly (which can be evident in utero) with intact cognition. Clinically it presents with delayed motor development, hypotonia, absent or reduced deep tendon reflexes, progressive muscle wasting and weakness and scoliosis.
Microcephaly-congenital cataract-psoriasiform dermatitis syndrome (ORPHA:488168)
A rare sterol biosynthesis disorder characterized by microcephaly, bilateral congenital cataract, mild developmental delay, growth delay with short stature, psoriasiform dermatitis of variable severity, and immune dysregulation. Behavioral disorder, joint contractures, and arthralgia have also been described.
Microcephaly-corpus callosum and cerebellar vermis hypoplasia-facial dysmorphism-intellectual disability syndrom (ORPHA:500159)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay and moderate to severe intellectual disability, as well as variable other manifestations, such as macro- or microcephaly, epilepsy, hypotonia, behavioral problems, stereotypic movements, and facial dysmorphism (including arched eyebrows, long palpebral fissures, prominent nasal bridge, upturned nose, dysplastic ears, and broad mouth), among others. Brain imaging may show cerebellar anomalies, hypoplastic corpus callosum, enlarged ventricles, polymicrogyria, or white matter abnormalities.
Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome (ORPHA:457284)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by variable degrees of developmental delay and intellectual disability with poor or absent speech, hypotonia, hypoplastic or absent corpus callosum, and facial dysmorphism (such as long face, frontal bossing, hypertelorism, downslanting palpebral fissures, and tented upper lip). Additional reported features include microcephaly, seizures, gait ataxia, scoliosis, and syndactyly of fingers, among others.
Microcephaly-deafness-intellectual disability syndrome (ORPHA:2533)
Microcephaly-deafness-intellectual disability syndrome is characterised by microcephaly, deafness, intellectual deficit and facial dysmorphism (facial asymmetry, prominent glabella, low-set and cup-shaped ears, protruding lower lip, micrognathia). It has been described in a mother and her son. The mode of inheritance is probably autosomal dominant.
Microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome (ORPHA:521445)
A rare genetic disease characterized by a highly variable phenotype comprising ocular anomalies (congenital glaucoma, myopia, retinal detachment, and/or Axenfeld-Rieger anomaly), congenital hypothyroidism, hearing loss, microcephaly, dental defects, kidney anomalies, cerebrovascular anomalies, and distal limb anomalies. Dysmorphic facial features may include square face with prominent jaw, broad flat nasal bridge, short philtrum, and prominent ears.
Microcephaly-facio-cardio-skeletal syndrome, Hadziselimovic type (ORPHA:217026)
Microcephaly-facio-cardio-skeletal syndrome, Hadziselimovic type is a rare syndrome with cardiac malformations (see this term), characterized by prenatal-onset growth retardation (low birth weight and short stature), hypotonia, developmental delay and intellectual disability associated with microcephaly and craniofacial (low anterior hairline, hypotelorism, thick lips with carp-shaped mouth, high-arched palate, low-set ears), cardiac (conotruncal heart malformations such as tetralogy of Fallot; see these terms) and skeletal (hypoplastic thumbs and first metacarpals) abnormalities.
Microcephaly-glomerulonephritis-marfanoid habitus syndrome (ORPHA:2172)
A rare intellectual disability syndrome characterized by intellectual deficit, marfanoid habitus, microcephaly, and glomerulonephritis. There have been no further reports since 1992.
Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome (ORPHA:457351)
A rare genetic disease characterized by microcephaly, global developmental delay, intellectual disability, abnormal muscle tone, and sensorineural hearing impairment. Additional variable manifestations include epilepsy, cortical visual impairment, gastrointestinal disturbances, growth restriction, scoliosis, as well as immunodeficiency and thrombocytopenia. Brain imaging may show cerebral atrophy, thin corpus callosum, and hypomyelination.