Kniest dysplasia is a rare form of dwarfism caused by a mutation in the COL2A1 gene on chromosome 12. The COL2A1 gene is responsible for producing type II collagen. The mutation of COL2A1 gene leads to abnormal skeletal growth and problems with hearing and vision. What characterizes Kniest dysplasia from other type II osteochondrodysplasia is the level of severity and the dumb-bell shape of shortened long tubular bones.This condition was first described by Dr. Wilhelm Kniest in 1952, publishing the case history of a 3 1⁄2 year-old girl. Dr. Kniest noticed that his patient had bone deformities and restricted joint mobility. The patient also had short stature and later developed blindness, resulting from retinal detachment and glaucoma. Upon analysis of the patients DNA in 1992, sequencing revealed deletion of a 28 base pair sequence encompassing a splice site in exon 12 and a G to A transition in exon 50 of the COL2A1 gene.This condition is very rare and occurs less than 1 in 1,000,000 people. Males and females have equal chances of having this condition. Currently, there is no cure for Kniest dysplasia. Alternative names for Kniest Dysplasia can include Kniest syndrome, swiss cheese cartilage syndrome, Kniest chondrodystrophy, or metatrophic dwarfism type II. Signs and symptoms
Because collagen plays an important role in the development of the body, people with Kniest Dysplasia will typically have their first symptoms at birth.
Genetics
Genetic diseases of thiamine transport are rare but serious. Thiamine responsive megaloblastic anemia syndrome (TRMA) with diabetes mellitus and sensorineural deafness is an autosomal recessive disorder caused by mutations in the gene SLC19A2, a high affinity thiamine transporter. TRMA patients do not show signs of systemic thiamine deficiency, suggesting redundancy in the thiamine transport system. This has led to the discovery of a second high-affinity thiamine transporter, SLC19A3. Leigh disease (subacute necrotising encephalomyelopathy) is an inherited disorder that affects mostly infants in the first years of life and is invariably fatal. Pathological similarities between Leigh disease and WE led to the hypothesis that the cause was a defect in thiamine metabolism. One of the most consistent findings has been an abnormality of the activation of the pyruvate dehydrogenase complex.Mutations in the SLC19A3 gene have been linked to biotin-thiamine responsive basal ganglia disease, which is treated with pharmacological doses of thiamine and biotin, another B vitamin. Other disorders in which a putative role for thiamine has been implicated include subacute necrotising encephalomyelopathy, opsoclonus myoclonus syndrome (a paraneoplastic syndrome), and Nigerian seasonal ataxia (or African seasonal ataxia). In addition, several inherited disorders of ThDP-dependent enzymes have been reported, which may respond to thiamine treatment. Pathophysiology
Thiamine in the human body has a half-life of 18 days and is quickly exhausted, particularly when metabolic demands exceed intake. A derivative of thiamine, thiamine pyrophosphate (TPP), is a cofactor involved in the citric acid cycle, as well as connecting the breakdown of sugars with the citric acid cycle.