Pyruvate kinase deficiency is a genetic blood disorder characterized by low levels of an enzyme called pyruvate kinase , which is used by red blood cells. Without pyruvate kinase, red blood cells break down too easily, resulting in low levels of these cells (hemolytic anemia). The signs and symptoms of the disease may vary greatly from person to person. However, they usually include jaundice, enlargement of the spleen , and mild or severe hemolysis (red cell breakdown), leading to anemia. In some cases, the problems may first appear while in utero, causing a condition in which abnormal amounts of fluid build up in two or more body areas of the fetus (hydrops fetalis).

Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Specifically, pyruvate kinase deficiency is a common cause of a type of inherited hemolytic anemia called hereditary nonspherocytic hemolytic anemia. In hereditary nonspherocytic hemolytic anemia, the red blood cells do not assume a spherical shape as they do in some other forms of hemolytic anemia. Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), extreme tiredness (fatigue), shortness of breath (dyspnea), and a rapid heart rate (tachycardia).

Chronic icterus, gallstones, iron overload and splenomegaly are common findings. Etiology Erythrocyte PK deficiency is caused by mutations in the PKLR gene (1q22). To date, more than 290 mutations in PKLR have been reported. PK is a key regulatory enzyme of glycolysis and two major metabolic abnormalities result from PK deficiency: ATP depletion and increased 2,3-diphosphoglycerate (2,3-DPG) content. ... Red blood cell morphology is essentially normal. PK deficiency is diagnosed by measuring PK enzymatic activity. Importantly, due to the fact that the enzymatic activity is red cell age-dependent, a deficiency of PK may be masked by reticulocytosis. ... Bone marrow transplantation can cure PK deficiency but is rarely performed.

"Six Children with Pyruvate Kinase Deficiency from One Small Town: Molecular Characterization of the PK-LR Gene". The Journal of Pediatrics . 159 (4): 695–697. doi : 10.1016/j.jpeds.2011.05.043 .

Pallister-Killian syndrome (PKS) is a rare multiple congenital anomaly/intellectual deficit syndrome caused by mosaic tissue-limited tetrasomy for chromosome 12p. ... Severe intellectual deficit, pigmentary skin anomalies, deafness and seizures are frequent signs. Etiology Patients with PKS have mosaïcism for a supernumerary isochromosome 12p, resulting in four copies of the short arm of chromosome 12 instead of the normal two.

Pallister-Killian mosaic syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by extremely weak muscle tone (hypotonia) in infancy and early childhood, intellectual disability, distinctive facial features, sparse hair, areas of unusual skin coloring (pigmentation), and other birth defects. Most babies with Pallister-Killian mosaic syndrome are born with significant hypotonia, which can cause difficulty breathing and problems with feeding. Hypotonia also interferes with the normal development of motor skills such as sitting, standing, and walking. About 30 percent of affected individuals are ultimately able to walk without assistance.

Pallister-Killian syndrome Other names Tetrasomy 12p mosaicism, Pallister mosaic aneuploidy syndrome Pallister–Killian syndrome (also tetrasomy 12p mosaicism or Pallister mosaic aneuploidy syndrome ) is an extremely rare genetic disorder occurring in humans . Pallister–Killian occurs due to the presence of the anomalous extra isochromosome 12p, the short arm of the twelfth chromosome . This leads to the development of tetrasomy 12p. [1] Because not all cells have the extra isochromosome, Pallister–Killian is a mosaic condition (more readily detected in skin fibroblasts ). It was first described by Philip Pallister in 1977 and further researched by Maria Teschler-Nicola and Wolfgang Killian in 1981. [2] Contents 1 Presentation 2 Causes 3 Diagnosis 4 See also 5 References 6 External links Presentation [ edit ] This section does not cite any sources . Please help improve this section by adding citations to reliable sources .

Pallister-Killian mosaic syndrome is a multi-system disorder that is characterized by extremely weak muscle tone (hypotonia) in infancy and early childhood, intellectual disability, distinctive facial features, sparse hair, areas of unusual skin coloring (pigmentation), and other birth defects. The signs and symptoms of Pallister-Killian mosaic syndrome can vary, although most documented cases of people with the syndrome have severe to profound intellectual disability and other serious health problems. Pallister-Killian mosaic syndrome is usually caused by the presence of an abnormal extra chromosome 12 called isochromosome 12p. An isochromosome is a chromosome with two identical arms. Normal chromosomes have one long (q) arm and one short (p) arm, but isochromosomes have either two q arms or two p arms. Isochromosome 12p is a version of chromosome 12 made up of two p arms.

A number sign (#) is used with this entry because posterior amorphous corneal dystrophy (PACD) is a chromosome 12q21.33 contiguous gene deletion syndrome. Clinical Features Carpel et al. (1977) observed a posterior corneal dystrophy characterized by irregular sheetlike areas of opacification with involvement of the Descemet membrane and, in some instances, alterations of the normal endothelial mosaic. There was no evidence of stromal edema, but a uniform thinning was present. The disorder was present in persons in 3 generations, with male-to-male transmission. Dunn et al. (1984) reported 8 members of a family spanning 5 generations with posterior amorphous corneal dystrophy.

Human disease Posterior amorphous corneal dystrophy Specialty Ophthalmology Posterior amorphous corneal dystrophy (PACD) is a rare form of corneal dystrophy . It is not yet linked to any chromosomal locus. The first report describing this dystrophy dates back to 1977. [1] References [ edit ] ^ Carpel EF, Sigelman RJ, Doughman DJ (May 1977). "Posterior amorphous corneal dystrophy". Am. J. Ophthalmol. 83 (5): 629–32. doi : 10.1016/0002-9394(77)90127-1 . PMID 301356 . External links [ edit ] Classification D OMIM : 612868 MeSH : C567546 C567546, C567546 v t e Types of corneal dystrophy Epithelial and subepithelial Epithelial basement membrane dystrophy Gelatinous drop-like corneal dystrophy Lisch epithelial corneal dystrophy Meesmann corneal dystrophy Subepithelial mucinous corneal dystrophy Bowman's membrane Reis–Bucklers corneal dystrophy Thiel-Behnke dystrophy Stroma Congenital stromal corneal dystrophy Fleck corneal dystrophy Granular corneal dystrophy Lattice corneal dystrophy Macular corneal dystrophy Posterior amorphous corneal dystrophy Schnyder crystalline corneal dystrophy Descemet's membrane and endothelial Congenital hereditary endothelial dystrophy Fuchs' dystrophy Posterior polymorphous corneal dystrophy X-linked endothelial corneal dystrophy This article about the eye is a stub . You can help Wikipedia by expanding it . v t e

A number sign (#) is used with this entry because of evidence that gelatinous drop-like corneal dystrophy (GDLD) can be caused by homozygous or compound heterozygous mutation in the M1S1 gene (TACSTD2; 137290), which encodes the monoclonal antibody-defined, tumor-associated antigen GA733-1, on chromosome 1p32. Description Gelatinous drop-like corneal dystrophy is an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness. Clinical manifestations, which appear in the first decade of life, include blurred vision, photophobia, and foreign-body sensation. By the third decade, raised, yellowish-gray, gelatinous masses severely impair visual acuity, and lamellar keratoplasty is required for most patients (summary by Tsujikawa et al., 1999). Clinical Features Corneal amyloidosis is characterized by central raised gelatinous masses, making the surface of the cornea resemble a mulberry.

Gelatinous drop-like corneal dystrophy Other names Subepithelial amyloidosis of the cornea A completely opaque cornea with multiple drop-like nodular opacities. Some blood vessels are present in the opaque cornea Apple green dichroism of subepithelial deposition of amyloid viewed under polarized light. Congo red stain. Gelatinous drop-like corneal dystrophy , also known as amyloid corneal dystrophy, is a rare form of corneal dystrophy . The disease was described by Nakaizumi as early as 1914. [1] Contents 1 Presentation 2 Genetics 3 Diagnosis 4 Treatment 5 References 6 External links Presentation [ edit ] The main pathological features in this dystrophy are mulberry-shaped gelatinous masses beneath the corneal epithelium. Patients suffer from photophobia, foreign body sensation in the cornea.

A number sign (#) is used with this entry because of evidence that lattice corneal dystrophy type I (LCD1) is caused by heterozygous mutation in the gene encoding keratoepithelin (TGFBI; 601692) on chromosome 5q31. Heterozygous mutation in the TGFBI gene causes several other forms of autosomal dominant corneal dystrophy. Clinical Features Frayer and Blodi (1959) described a family. Grayish lines like cotton threads are mainly limited to a zone between the center of the cornea and the periphery, usually not extending to the limbus. Rounded dots with distinct borders are scattered everywhere. The cornea between opacities is relatively clear. Visual activity is usually normal in childhood. In this and the granular type, the histologic findings are hyaline degeneration and absence of acid mucopolysaccharide deposition.

Lattice corneal dystrophy type I is an eye disorder that affects the clear, outer covering of the eye called the cornea. The cornea must remain clear for an individual to see properly; however, in lattice corneal dystrophy type I, protein clumps known as amyloid deposits cloud the cornea, which leads to vision impairment. The cornea is made up of several layers of tissue, and in lattice corneal dystrophy type I, the deposits form in the stromal layer. The amyloid deposits form as delicate, branching fibers that create a lattice pattern. Affected individuals often have recurrent corneal erosions, which are caused by separation of particular layers of the cornea from one another.

A number sign (#) is used with this entry because of evidence that lattice type IIIA corneal dystrophy (CDL3A) is caused by heterozygous mutation in the TGFBI gene (601692) on chromosome 5q31. The TGFB1 gene is mutant in several other forms of corneal dystrophy, including Reis-Bucklers corneal dystrophy (CDRB; 608470), Thiel-Behnke corneal dystrophy (CDTB; 602082), lattice type I corneal dystrophy (CDL1; 122200), Avellino corneal dystrophy (ACD; 607541), and Groenouw type I corneal dystrophy (CDGG1; 121900). Clinical Features Yamamoto et al. (1998) used the designation lattice corneal dystrophy type IIIA for a disorder that resembled type III (204870) clinically but differed in that its age of onset was late (70 to 90 years) and it had an autosomal dominant inheritance pattern; see 601692.0005. Molecular Genetics Yamamoto et al. (1998) identified a mutation in the TGFBI gene (601692.0005) that caused type IIIA lattice corneal dystrophy. Stix et al. (2005) identified a missense mutation in the TGFBI gene (601692.0010) in a family with type IIIA lattice corneal dystrophy and corneal amyloid deposits that contained proteolytic fragments of keratoepithelin.

Lattice corneal dystrophy type 1 (LCD1) is an eye disorder that affects the cornea , the clear outer covering of the eye. In order to see properly, the cornea must remain clear. In LCD1, a protein, known as amyloid, builds up in a layer of the cornea called the stroma. Symptoms usually become apparent in childhood or adolescence and may include separation of layers of the cornea (corneal erosions), decreased vision, photosensitivity , and eye pain. LCD1 is caused by mutations in the TGFBI gene and is inherited in an autosomal dominant manner. Treatment focuses on relieving erosions with antibiotics and bandage contact lenses.

A number sign (#) is used with this entry because of evidence that Reis-Bucklers corneal dystrophy (CDRB, or CDB1) is caused by heterozygous mutation in the TGFBI gene (601692) on chromosome 5q31. The TGFBI gene is mutant in several other forms of corneal dystrophy, including Thiel-Behnke corneal dystrophy (CDTB, or CDB2; 602082), lattice type I corneal dystrophy (CDL1; 122200), lattice type IIIA corneal dystrophy (CDL3A; 608471), Avellino corneal dystrophy (ACD; 607541), and Groenouw type I corneal dystrophy (CDGG1; 121900). Clinical Features Paufique and Bonnet (1966) described a family with members in 3 generations affected by Reis-Buckler corneal dystrophy. Most of the affected persons also had strabismus. The cornea presented a 'dusty' opacity and a rough map-like surface with a peripheral condensation ring separated from the limbus by a narrow strip of normal cornea. The lesions are primarily in Bowman membrane with secondary involvement of the epithelium and superficial part of the stroma.

Reis-Bücklers corneal dystrophy Other names Corneal dystrophy of Bowman layer, type I Reis-Bücklers corneal dystrophy. Reticular opacity in the superficial cornea Specialty Ophthalmology Reis-Bücklers corneal dystrophy , is a rare, corneal dystrophy of unknown cause, in which the Bowman's layer of the cornea undergoes disintegration. The disorder is inherited in an autosomal dominant fashion, and is associated with mutations in the gene TGFB1 . Reis-Bücklers dystrophy causes a cloudiness in the corneas of both eyes, which may occur as early as 1 year of age, but usually develops by 4 to 5 years of age. It is usually evident within the first decade of life. This cloudiness, or opacity, causes the corneal epithelium to become elevated, which leads to corneal opacities.

A benign inborn error of glycogen metabolism. It is the mildest form of GSD due to PhK deficiency. Epidemiology Prevalence is unknown. Clinical description The disease manifests in childhood. Patients have marked hepatomegaly and mild muscular hypotonia. Hypoglycemia may occur only after prolonged fasting. These symptoms improve with age and adults are generally asymptomatic. Etiology Phosphorylase kinase (PhK) is an enzyme which plays a key role in the regulation of glycogenolysis as it is required for glycogen phosphorylase activation.

Fryns syndrome is a condition that affects the development of many parts of the body. The features of this disorder vary widely among affected individuals and overlap with the signs and symptoms of several other disorders. These factors can make Fryns syndrome difficult to diagnose. Most people with Fryns syndrome have a defect in the muscle that separates the abdomen from the chest cavity (the diaphragm ). The most common defect is a congenital diaphragmatic hernia, which is a hole in the diaphragm that develops before birth. This hole allows the stomach and intestines to move into the chest and crowd the heart and lungs.

A rare multiple congenital anomaly syndrome characterized by dysmorphic facial features, congenital diaphragmatic hernia, pulmonary hypoplasia, and distal limb hypoplasia, in addition to variable expression of additional malformations. Epidemiology The birth prevalence of Fryns syndrome (FS) has been estimated at 1/14,000 births. Clinical description Polyhydramnios is often noted during pregnancy and neonates present with a spectrum of various malformations at birth. The classical features of FS include CDH (unilateral in 75% of cases), dysmorphic craniofacial features (coarse facies, ocular hypertelorism, microphthalmia, low-set, poorly formed ears, a broad and flat nasal bridge, thick nasal tip with anteverted nares, long philtrum, tented upper lip, macrostomia and microretrognathia), and limb malformations (mainly distal limb hypoplasia that includes short and broad hands, short digits, short terminal phalanges, hypoplastic or absent nails, and clinodactyly). Thorax is small with widely spaced nipples. Brain (ventricular dilation, hydrocephalus) and cardiac malformations (atrial and ventricular septal defects, aortic abnormalities) are reported frequently in affected individuals.

Fryns syndrome Other names Diaphragmatic hernia-abnormal face-distal limb anomalies syndrome Fryns syndrome is inherited in an autoosomal recessive manner. Specialty Medical genetics Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome that is usually lethal in the neonatal period. [1] Fryns (1987) reviewed the syndrome. [2] Contents 1 Presentation 2 Cytogenetics 3 Diagnosis 4 Epidemiology 5 Cases 6 References 7 External links Presentation [ edit ] Usually associated with diaphragmatic hernia , pulmonary hypoplasia , imperforate anus , micropenis , bilateral cryptorchidism , cerebral ventricular dilation , camptodactyly , agenesis of sacrum , low-set ear. [ citation needed ] Cytogenetics [ edit ] In a newborn boy thought to have Fryns syndrome, Clark and Fenner-Gonzales (1989) found mosaicism for a tandem duplication of 1q24-q31.2. [3] They suggested that the gene for this disorder is located in that region. However, de Jong et al. (1989), Krassikoff and Sekhon (1990), and Dean et al. (1991) found possible Fryns syndrome associated with anomalies of chromosome 15 , chromosome 6 , chromosome 8 and chromosome 22 , respectively. [4] [5] [6] Thus, these cases may all represent mimics of the mendelian syndrome and have no significance as to the location of the gene for the recessive disorder. [ citation needed ] By array CGH, Slavotinek et al. (2005) screened patients with DIH and additional phenotypic anomalies consistent with Fryns syndrome for cryptic chromosomal aberrations. [7] They identified submicroscopic chromosome deletions in 3 probands who had previously been diagnosed with Fryns syndrome and had normal karyotyping with G-banded chromosome analysis . Two female infants were found to have microdeletions involving 15q26.2 (see 142340), and 1 male infant had a deletion in band 8p23.1 (see 222400). Diagnosis [ edit ] Prenatal Diagnosis: Aymé, et al. (1989) reported prenatal diagnosis of Fryns syndrome by sonography between 24 and 27 weeks. [8] Manouvrier-Hanu et al. (1996) described the prenatal diagnosis of Fryns syndrome by ultrasonographic detection of diaphragmatic hernia and cystic hygroma. [9] The diagnosis was confirmed after termination of the pregnancy.

Description Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome that is usually lethal in the neonatal period (Alessandri et al., 2005). Fryns (1987) reviewed the syndrome. Also see Tonne-Kalscheuer syndrome (300978), an X-linked disorder with overlapping features. Clinical Features Fryns et al. (1979) reported 2 stillborn sisters with a multiple congenital anomaly syndrome characterized by coarse facies with cloudy corneae, diaphragmatic defects, absence of lung lobulation, and distal limb deformities. A sporadic case was reported by Goddeeris et al. (1980). Fitch (1988) claimed that she and her colleagues were the first to describe this disorder. In 1978 they reported a single infant, born of second-cousin parents, who had absent left hemidiaphragm, hydrocephalus, arhinencephaly, and cardiovascular anomalies (Fitch et al., 1978).

Fryns syndrome is a condition that affects the development of many parts of the body. Signs and symptoms vary widely among affected individuals. Many indiivduals with this condition have defects of the diaphragm such as a congenital diaphragmatic hernia (a hole in the diaphragm present at birth). This may allow the stomach and intestines to move into the chest, which can result in pulmonary hypoplasia (underdevelopment of the lungs). Other signs and symptoms may include abnormalities of the fingers and toes; distinctive facial features; severe developmental delay and intellectual disability; and abnormalities of the brain, cardiovascular system, gastrointestinal system, kidneys, and genitalia. survival beyond the neonatal period is rare. The cause of Fryns syndrome is not known, but it is thought to be genetic and appears to be inherited in an autosomal recessive manner.

A number sign (#) is used with this entry because of evidence that the marfanoid-progeroid-lipodystrophy syndrome (MFLS) is caused by heterozygous mutation occurring in or affecting exon 64 of the FBN1 gene (134797) on chromosome 15q21. Description The marfanoid-progeroid-lipodystrophy syndrome (MFLS) is characterized by congenital lipodystrophy, premature birth with an accelerated linear growth disproportionate to weight gain, and progeroid appearance with distinct facial features, including proptosis, downslanting palpebral fissures, and retrognathia. Other characteristic features include arachnodactyly, digital hyperextensibility, myopia, dural ectasia, and normal psychomotor development (Takenouchi et al., 2013). Takenouchi et al. (2013) noted phenotypic overlap with Marfan syndrome (154700) and Shprintzen-Goldberg craniosynostosis syndrome (182212). Clinical Features Verloes et al. (1998) described a 1-year-old girl with an 'unclassifiable' form of connective tissue disorder.

Progeroid and marfanoid aspect-lipodystrophy syndrome is a rare systemic disease characterized by a neonatal progeroid appearance (not associated with other manifestations of premature aging) associated with facial dysmorphism (e.g. macrocephaly or arrested hydrocephaly, proptosis, downslanting palpebral fissures, retrognathia), generalized, extreme, congenital lack of subcutaneous fat tissue (except in the breast and iliac region) and incomplete signs of Marfan syndrome (mainly severe myopia, joint hyperextensibility and arachnodactyly). Metabolic disturbances are not associated.

Myotonic dystrophy type 1 (MD1), one of the two types of myotonic dystrophy , is an inherited type of muscular dystrophy that affects the muscles and other body systems (e.g., heart, eyes, endocrine system , and central nervous system). MD1 has three forms that somewhat overlap: the mild form, classic form, and congenital form (present at birth). The mild form has the least severe symptoms of the different forms of MD1 and is associated with a normal life span. The classic form is characterized by muscle weakness and wasting, prolonged muscle tensing ( myotonia ), cataract, and often, abnormal heart function. Adults with the classic form may become physically disabled and may have a shortened life span.

Summary Clinical characteristics. Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central nervous system. The clinical findings, which span a continuum from mild to severe, have been categorized into three somewhat overlapping phenotypes: mild, classic, and congenital. Mild DM1 is characterized by cataract and mild myotonia (sustained muscle contraction); life span is normal. Classic DM1 is characterized by muscle weakness and wasting, myotonia, cataract, and often cardiac conduction abnormalities; adults may become physically disabled and may have a shortened life span. Congenital DM1 is characterized by hypotonia and severe generalized weakness at birth, often with respiratory insufficiency and early death; intellectual disability is common.

Myotonic dystrophy is part of a group of inherited disorders called muscular dystrophies. It is the most common form of muscular dystrophy that begins in adulthood. Myotonic dystrophy is characterized by progressive muscle wasting and weakness. People with this disorder often have prolonged muscle contractions (myotonia) and are not able to relax certain muscles after use. For example, a person may have difficulty releasing their grip on a doorknob or handle.

A rare genetic multi-system disorder characterized by a wide range of muscle-related manifestations (muscle weakness, myotonia, early onset cataracts (before age 50) and systemic manifestations (cerebral, endocrine, cardiac, gastrointestinal tract, uterus, skin and immunologic involvement) that vary depending on the age of onset. The very wide clinical spectrum ranges from lethal presentations in infancy to mild, late-onset disease. Epidemiology It is the most frequent adult muscular dystrophy and has an estimated prevalence ranging from 1/215,000 in Taiwan to 1/5,500 in Croatia. It appears to be more prevalent in the Saguenay-Lac-St-Jean region-Quebec, Canada (1/600), suggesting a founder effect. The disease occurs worldwide. Clinical description The age of onset is highly variable, from prenatal to adulthood.