TaoMedAI/RareMedData huggingface dataset:
Congenital intrinsic factor deficiency (ORPHA:332)
Congenital intrinsic factor deficiency (IFD) is a rare disorder of vitamin B12 (cobalamin) absorption that is characterized by megaloblastic anemia and neurological abnormalities.
Epidemiology
The incidence and prevalence of IFD are unknown. Fewer than 100 cases have been reported in the literature and fewer than 50 cases have been confirmed molecularly.
Clinical description
The disease usually manifests before the age of 5 but patients in their 10th and 30th decade of life have also been reported. It manifests with failure to thrive and symptoms of anemia (e.g. asthenia, weakness, headache, infections). If untreated, neurological damage may occur such as peripheral neuropathy, subacute combined degeneration of the spinal cord and/or ataxia. Neurological symptoms may include muscular weakness and abnormal gait.
Etiology
Patients have bi-allelic mutations in the GIF gene on chromosome 11 encoding the gastric Intrinsic Factor (IF), a protein necessary for the absorption of vitamin B12. GIF mutations lead to impaired IF synthesis and thus vitamin B12 (cobalamin) malabsorption and deficiency.
Diagnostic methods
Diagnosis depends on blood tests that show low serum levels of cobalamin and megaloblastic anemia (decreased red blood cell count and increased mean corpuscular volume). Nowadays, measurement of transcobalamin-bound cobalamin (holo-transcobalamin) in serum is preferred to measurement of total serum cobalamin. As cobalamin deficiency affects enterocyte function, thereby enhancing cobalamin malabsorption, it is recommended to treat first with cobalamin in order to reestablish proper enterocyte function before performing any diagnostic malabsorption testing. Acid secretion is usually present but patients may show low or absent IF amounts in the gastric juice. Urine tests show increased amounts of methylmalonic acid (MMA) and total homocysteine (tHcy). There are no auto-antibodies directed against the gastric parietal cells antigen H+/K+ ATPase (anti-GPC) and intrinsic factor (anti-IFA). Commercial genetic testing is not yet available.
Differential diagnosis
Differential diagnosis includes Imerslund-Gräsbeck syndrome, transcobalamin II deficiency, cblF defect, and acquired pernicious anemia (see these terms), which is caused by autoimmunity or Helicobacter infection.
Antenatal diagnosis
Antenatal diagnosis is not available.
Genetic counseling
Both sporadic cases and familial cases with autosomal recessive transmission have been reported.
Management and treatment
The standardized treatment consists of weekly to monthly intramuscular injections of vitamin B12. Hydroxocobalamin injections are preferred over cyanocobalamin as the latter may cause muscular pain and have ophthalmo-neurological side effects. Oral vitamin B12 supplementation may be ineffective and not recommended.
Prognosis
Prognosis is good. Without treatment, neurological and hematopoietic complications can occur that can also be fatal.

                            Last update: 
                            September 2011


                            - Expert reviewer(s): 
                            Dr Stephan TANNER
Congenital isolated ACTH deficiency (ORPHA:199296)
A rare endocrine disease characterized by neonatal hypoglycemia, prolonged cholestatic jaundice, and seizures. Typical are low plasma ACTH and cortisol levels in the absence of structural pituitary defects, and sometimes low partial growth hormone deficiency is associated.
Congenital knee dislocation (ORPHA:295034)
A rare congenital limb malformation characterized by either hyperextension of the knee greater than 0° associated with limited flexion (congenital genu recurvatum) or permanent knee flexion with limited extension (congenital genu flexum). It can be unilateral or bilateral and may occur as an isolated malformation, be associated with other orthopedic abnormalities (like developmental dysplasia of the hip or clubfoot), or be part of a syndrome (e. g. Larsen's syndrome, arthrogryposis multiplex congenita).
Congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome (ORPHA:495875)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, absent scrotum or labia majora, absent or underdeveloped nipples and a tuft of hair extruding from the lactiferous ducts, bilateral corneal opacities, and dysmorphic craniofacial features (microcephaly, short forehead, and ear abnormalities, among others). Patients also show horizontal nystagmus and ataxic gait. Brain MRI reveals small cerebellar hemispheres and vermis and a small pons.
Congenital lactase deficiency (ORPHA:53690)
Congenital lactase deficiency is a rare severe gastrointestinal disorder in newborns primarily reported in Finland and characterized clinically by watery diarrhea on feeding with breast-milk or lactose-containing formula.
Congenital laryngeal cyst (ORPHA:141124)
Congenital laryngeal cyst is a rare larynx anomaly characterized by a cyst involving the larynx or supraglottis locations, such as the epiglottis and vallecula. Timing and severity of presentation depend on the size of the cyst and its proximity to the glottis and range from severe prenatal airway obstruction leading to polyhydramnios and pulmonary hypoplasia to postnatal inspiratory stridor associated with muffled cry, hoarseness and cyanotic episodes, and to feeding difficulties and failure to thrive. It can be associated with laryngomalacia.
Congenital laryngeal palsy (ORPHA:137932)
Congenital laryngeal palsy is a rare larynx anomaly characterized by unilateral or bilateral paralysis of the vocal cords as a result of dysfunction of the motor nerve supply to the larynx. Patients typically present at birth (or shortly thereafter) with stridor, weak or breathy cry, dysphonia or aphonia, feeding or aspiration difficulties and, occasionally, respiratory compromise. Neurological disease, masses that cause compression and aberrant vessels are often associated. Most cases resolve spontaneously over 6-12 months.
Congenital laryngomalacia (ORPHA:2373)
A rare larynx anomaly characterized by an inward collapse of supraglottic airway during inspiration, which manifests with an inspiratory stridor and might be associated with feeding difficulties, swallowing dysfunction, failure to thrive, and respiratory distress.
Congenital left ventricular aneurysm (ORPHA:1055)
A rare congenital non-syndromic heart malformation characterized by a bulging of the left ventricular wall, connected to the left ventricle by a wide neck (with a ratio of the connection to the body of the anomaly >1). The dimensions of aneurysms have been described as small as 0.5 cm in diameter and as big as 8x9 cm in size. Most frequent locations are the left ventricular apex and the perivalvular area. Aneurysms can be a- or dyskinetic or show almost normal contractility. Patients may remain asymptomatic or present with systemic embolization, congestive heart failure, valvular regurgitation, ventricular wall rupture, ventricular tachycardia, or sudden cardiac death.
Congenital lethal erythroderma (ORPHA:1954)
A rare skin disorder characterized by erythrodermic, peeling skin from birth with no obvious nail or hair-shaft abnormalities and other associated anomalies including diarrhea, failure to thrive and severe hypoalbuminaemia resistant to correction by enteral or intravenous supplementation. An autosomal recessive mode of inheritance is highly probable. The prognosis is poor and infants die in the first months of life. There have been no further descriptions in the literature since 1992.
Congenital lethal myopathy, Compton-North type (ORPHA:210163)
Congenital lethal myopathy, Compton-North type is a rare, genetic, lethal, non-dystrophic congenital myopathy disorder characterized, antenatally, by fetal akinesia, intrauterine growth restriction and polyhydramnios, and, following birth, by severe neonatal hypotonia, severe generalized skeletal, bulbar and respiratory muscle weakness, multiple flexion contractures, and normal creatine kinase serum levels. Ultrastructurally, loss of integrin alpha7, beta2-syntrophin and alpha-dystrobrevin from the muscle sarcolemma and disruption of sarcomeres with disorganization of the Z band are observed.
Congenital limbs-face contractures-hypotonia-developmental delay syndrome (ORPHA:562528)
A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by severe congenital contractures of the limbs and face, hypotonia, neonatal respiratory distress, and global developmental delay. Dysmorphic facial features include downslanting palpebral fissures, broad nasal bridge, large nares, long philtrum, and deep nasolabial folds, among others. Limb deformities (camptodactyly, clubfoot), short neck, scoliosis, as well as seizures have also been reported. Brain MRI may show cerebral and cerebellar atrophy in some cases.
Congenital lobar emphysema (ORPHA:1928)
A respiratory abnormality characterized by respiratory distress due to hyperinflation of one or more affected lobes of the lung.
Epidemiology
It is a rare disease with the birth prevalence being 1/20,000 to 1/30,000.
Clinical description
Most cases present in the neonatal period or in early infancy. Patients with less severe manifestations may present in early childhood or rarely in adulthood. Clinical picture can range from asymptomatic or mildly symptomatic to severe respiratory impairment requiring immediate intervention. Symptomatic patients present with asymmetric chest wall expansion, respiratory distress, dyspnea, tachycardia, cyanosis, and failure to thrive. The left upper lobe is most commonly affected (41%) followed by the right middle lobe (34%) and the right upper lobe (21%). CLE can occur in association with cardiac malformations in 15 to 20% cases.
Etiology
About 50% of cases have no identifiable etiology; however an abnormality or absence of cartilaginous rings, intrinsic obstruction caused by redundant mucosa, extrinsic obstruction (vascular or bronchial) or hyperinflation alone might explain the CLE. Polyalveolar lobe has also been reported as a cause of CLE.
Diagnostic methods
Chest X ray and CT scan are the key imaging modalities used for diagnosis. Chest X ray shows hyperlucent affected lobes with mediastinal shift and collapse of ipsilateral unaffected segments. CT scan provides details of affected lobes and vascular involvement. Echocardiography to detect concomitant heart disease can also be performed.
Differential diagnosis
Respiratory distress and radiolucency in chest X rays can lead to a misdiagnosis of tension pneumothorax. Differential diagnoses also include congenital pulmonary airway malformation, pneumonia, bronchiolitis and foreign body aspiration.
Antenatal diagnosis
Prenatal diagnosis can be made with ultrasonography by identifying hyperechoic areas in fetal lung and Magnetic Resonance Imaging identify uniform T2 hyperintensity compared to normal lung.
Management and treatment
Lobectomy of affected lobes is the widely accepted form of management with a satisfactory outcome. Asymptomatic or mildly symptomatic cases can be managed conservatively but follow up is necessary. Thoracoscopic resection has been attempted and seems to have better post operative outcomes.
Prognosis
Asymptomatic cases may regress spontaneously. Prompt diagnosis and surgical intervention usually provide good long term outcome in symptomatic cases. In some cases, CLE can be lethal.

                            Last update: 
                            June 2019


                            - Expert reviewer(s): 
                            Pr Daniele CATANEO
Congenital macroglossia (ORPHA:2430)
A rare developmental defect during embryogenesis characterized by muscular hypertrophy, adenoid hyperplasia, or vascular malformation that results in an enlarged, often protruding, tongue. Complications include difficulty in swallowing, breathing and mastication, drooling, dental and skeletal deformities, such as malocclusion, open bite, asymmetry in maxillary and mandibular arches. It may be isolated or associated with genetic syndromes.
Congenital megacalycosis (ORPHA:93109)
Congenital megacalycosis is a rare renal malformation, characterized by non-obstructive dilation of the renal calyces as well as an increased calyceal number (12-20), with a normal renal pelvis, ureter, and bladder. It may be unilateral or bilateral and is usually asymptomatic unless complicated by nephrolithiasis and urinary tract infection.
Congenital mesoblastic nephroma (ORPHA:2665)
A rare renal tumor characterized by a unilateral, solitary, well demarcated, mesenchymal/myofibroblastic neoplasm occurring in very young children. Histopathologically, three subtypes (classic, cellular, and mixed) can be distinguished. The tumor most commonly involves the renal sinus and is typically discovered as a palpable abdominal mass. Patients may also present with hypertension or hematuria, rarely with hypercalcemia or hyperreninemia. Prenatal presentation, usually with polyhydramnios, is not infrequent. The most important prognostic factor is completeness of surgical resection. Overall, malignant potential is low and clinical outcome favorable.
Congenital microcephaly-severe encephalopathy-progressive cerebral atrophy syndrome (ORPHA:391376)
A rare, genetic, neurometabolic disorder characterized by severe, progressive microcephaly, severe to profound global development delay, intellectual disability, seizures (typically tonic and/or myoclonic and frequently intractable), hyperekplexia, and axial hypotonia with appendicular spasticity, as well as hyperreflexia, dyskinetic quadriplegia, and abnormal brain morphology (cerebral atrophy with variable additional features including ventriculomeglay, pons and/or cerebellar hypoplasia, simplified gyral pattern and delayed myelination). Cortical blindness, feeding difficulties and respiratory insufficiency may also be associated.
Congenital microcoria (ORPHA:566)
Congenital microcoria is a rare autosomal dominant ophthalmological disease caused by maldevelopment of the dilator muscle of the pupil that is characterized by small pupils (<2 mm in diameter) from birth, peripheral iris hypopigmentation and transillumination defects leading to errors of refraction (myopia, astigmatism) and sometimes juvenile open angle glaucoma.
Congenital microgastria (ORPHA:199293)
Congenital microgastria is a rare malformation where the embryological development of the stomach is interrupted, leading to an abnormally small foregut in newborns and characterized by extreme feeding intolerance and malnutrition along with growth retardation and death if untreated. It is usually associated with multiple congenital anomalies.
Congenital mitral stenosis (ORPHA:99057)
Congenital mitral stenosis is a congenital heart malformation comprising a spectrum of morphologically heterogeneous developmental anomalies that result in functional and anatomic obstruction of inflow into the left ventricle. The structure of the mitral valve is affected at the level of the supravalvular ring, annulus, leaflets or subvalvar components and include supra-valvular ring, leaflet fusion (intra-leaflet ring), mitral parachute deformity and papillary muscle abnormalities. It may be isolated or associated with other heart malformations. The clinical presentation depends on the degree of obstruction, the presence of regurgitation, the presence and severity of associated pulmonary hypertension, and the presence of associated heart malformations. It may present with symptoms and signs of low cardiac output and right ventricular failure such as pulmonary infections, failure to thrive, exertional dyspnoea, cough, cyanosis and congestive heart failure.
Congenital muscular alpha-dystroglycanopathy with brain and eye anomalies (ORPHA:352687)
Congenital muscular alpha-dystroglycanopathy with brain and eye anomalies (MDDGA) is a cobblestone lissencephaly characterized by and considered to be pathognomonic of a continuum of recessive autosomal disorders with brain, ocular and muscular involvement. MDDGA includes Walker-Warburg syndrome, muscle-eye-brain disease, Fukuyama muscular and cerebral dystrophy and muscle eye brain disease with bilateral multicystic leukodystrophy.
Congenital muscular dystrophy type 1B (ORPHA:98893)
Congenital muscular dystrophy type 1B is a rare, genetic neuromuscular disorder characterized by proximal and symmetrical muscle weakness (particularly of neck, sternomastoid, facial and diaphragm muscles), spinal rigidity, joint contractures (Achilles tendon, elbows, hands), generalized muscle hypertrophy and early respiratory failure (usually in the first decade of life). Patients typically present delayed motor milestones and grossly elevated serum creatine kinase levels, and with disease progression, forced expiratory abdominal squeeze and nocturnal hypoventilation.
Congenital muscular dystrophy with cerebellar involvement (ORPHA:370959)
A rare, congenital muscular dystrophy due to dystroglycanopathy characterized by proximal muscle weakness with a tendency for muscle hypertrophy and pseudohypertrophy, variable cognitive impairment, microcephaly, cerebellar hypoplasia with or without cysts, and other structural brain anomalies.
Congenital muscular dystrophy with hyperlaxity (ORPHA:371007)
Congenital muscular dystrophy with hyperlaxity is a rare, genetic neuromuscular disease characterized by congenital hypotonia, generalized, slowly progressive muscular weakness, and proximal joint contractures with distal joint hypermobility and hyperlaxity. Scoliosis or rigidity of the spine and delayed motor milestones are also frequently reported. Other manifestations include a long myopathic face and, in rare cases, respiratory failure, mild to moderate intellectual deficiency and short stature. Ambulation may be impaired with time.
Congenital muscular dystrophy with integrin alpha-7 deficiency (ORPHA:34520)
Congenital muscular dystrophy with integrin alpha-7 deficiency is a rare, genetic, congenital muscular dystrophy due to extracellular matrix protein anomaly characterized by early motor development delay and muscle weakness with mild elevation of serum creatine kinase, that may be followed by progressive disease course with predominantly proximal muscle weakness and atrophy, motor development regress, scoliosis and respiratory insufficiency.
Congenital muscular dystrophy with intellectual disability and severe epilepsy (ORPHA:329178)
A rare, fatal, inborn error of metabolism disorder characterized by respiratory distress and severe hypotonia at birth, severe global developmental delay, early-onset intractable seizures, myopathic facies with craniofacial dysmorphism (trigonocephaly/progressive microcephaly, low anterior hairline, arched eyebrows, hypotelorism, strabismus, small nose, prominent philtrum, thin upper lip, high-arched palate, micrognathia, malocclusion), severe, congenital flexion joint contractures and elevated serum creatine kinase levels. Scoliosis, optic atrophy, mild hepatomegaly, and hypoplastic genitalia may also be associated.
Congenital muscular dystrophy with intellectual disability (ORPHA:370968)
A rare, genetic, congenital muscular dystrophy due to dystroglycanopathy disorder characterized by a wide phenotypic spectrum which includes hypotonia and muscular weakness present at birth or early infancy and delayed or arrested motor development, associated with mild to severe intellectual disability and variable brain abnormalities on neuroimaging studies. Feeding difficulties, joint and spinal deformities, respiratory insufficiency, and ocular anomalies (e.g. strabismus, retinal dystrophy, oculomotor apraxia) may be associated. Decreased or absent alpha-dystroglycan on immunohistochemical muscle staining and elevated serum creatine kinase are observed.
Congenital muscular dystrophy without intellectual disability (ORPHA:370980)
A rare, genetic, congenital muscular dystrophy due to dystroglycanopathy characterized by a wide phenotypic spectrum which includes hypotonia and muscular weakness present at birth or early infancy, delayed or arrested motor development, and normal intellectual abilities with normal (or only mild abnormalities) neuroimaging studies. Feeding difficulties, joint and spinal deformities, and respiratory insufficiency may be associated. Decreased alpha-dystroglycan on immunohistochemical muscle staining and elevated serum creatine kinase are observed.
Congenital muscular dystrophy-infantile cataract-hypogonadism syndrome (ORPHA:1875)
Congenital muscular dystrophy-infantile cataract-hypogonadism syndrome is characterized by congenital muscular dystrophy, infantile cataract and hypogonadism. It has been described in seven individuals from an isolated Norwegian village and in one unrelated individual. Transmission appears to be autosomal recessive.
Congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome (ORPHA:486815)
A rare congenital muscular dystrophy characterized by neonatal hypotonia, life-threatening respiratory failure, and feeding difficulties, furthermore by delayed motor development, severe muscle weakness predominantly affecting axial muscles (leading to poor head control, rigid cervical spine, and severe scoliosis), generalized joint laxity with no or mild contractures, as well as dry skin with follicular hyperkeratosis. Serum creatine kinase is normal or slightly elevated. Muscle biopsy shows fiber size variability, rounded fibers with mild increase of endomysial connective tissue and adipose replacement, abundant minicore lesions, increase of centrally located nuclei, angular fibers, and cap lesions.
Congenital myasthenic syndrome (ORPHA:590)
Congenital myasthenic syndrome (CMS) is a group of genetic disorders of impaired neuromuscular transmission at the motor endplate characterized by fatigable muscle weakness.
Congenital myopathy with excess of thin filaments (ORPHA:98904)
A rare, genetic, congenital myopathy disorder characterized by variable degrees of muscular weakness, frequently associated with severe nemaline myopathy-like disease (including neonatal hypotonia, lack of spontaneous movements, feeding and swallowing difficulties, frequent respiratory infections, respiratory insufficiency, early death), and histopathologic findings of large, densely packed, subsarcolemmal accumulations of thin, actin-immunopositive filaments (with or without intranuclear nemaline rods) on muscle biopsy.
Congenital myopathy with internal nuclei and atypical cores (ORPHA:319160)
Congenital myopathy with internal nuclei and atypical cores is a rare genetic skeletal muscle disease characterized by neonatal hypotonia, distal more than proximal muscle weakness, progressive exercise intolerance with prominent myalgias, and mild-to-moderate overall motor impairment with preserved ambulation. Face, extraocular, cardiac, and respiratory muscles are unaffected. Mild cognitive impairment is also noted in most patients.
Congenital myopathy with myasthenic-like onset (ORPHA:424107)
Congenital myopathy with myasthenic-like onset is a rare, genetic, non-dystrophic myopathy characterized by fatigable muscle weakness associated with congenital myopathy. Patients present with axial hypotonia, myopathic facies with fatigable ptosis, feeding difficulties, delayed gross motor development and proximal limb weakness with a RYR1-related typical pattern of muscle involvement (i.e. severe involvement of the soleus muscle and sparring of the rectus femoris, sartorius, gracilis and semitendinous muscles). Scoliosis and frequent respiratory tract infections are additional observed features.
Congenital myopathy with reduced type 2 muscle fibers (ORPHA:544602)
A rare congenital myopathy characterized by neonatal onset of severe muscle weakness with selective atrophy/hypotrophy or absence of type II myofibers. Patients present at birth with hypotonia and respiratory failure, as well as mild facial and severe axial and proximal upper and lower limb weakness with areflexia and mild contractures. Eye movements and cardiac function are normal.