Sly syndrome, also called mucopolysaccharidosis type VII (MPS-VII), is an autosomal recessive lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase. This enzyme is responsible for breaking down large sugar molecules called glycosaminoglycans. The inability to break down GAGs leads to a buildup in many tissues and organs of the body. The severity of the disease can vary widely.
Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.
Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within the cells that help build bone, cartilage, tendons, corneas, skin and connective tissue. GAGs are also found in the fluids that lubricate joints.
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce additional normal blood cells. HSCT may be autologous, syngeneic, or allogeneic.
Lysosomal storage diseases are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective due to a mutation, the large molecules accumulate within the cell, eventually killing it.
Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare lifelong genetic disease that mainly affects the brain and spinal cord. It is caused by a problem with how the body breaks down certain large sugar molecules called glycosaminoglycans (also known as GAGs or mucopolysaccharides). In children with this condition, these sugar molecules build up in the body and eventually lead to damage of the central nervous system and other organ systems.
Cell therapy is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues.
Morquio syndrome, also known as mucopolysaccharidosis type IV (MPS IV), is a rare metabolic disorder in which the body cannot process certain types of sugar molecules called glycosaminoglycans (AKA GAGs, or mucopolysaccharides). In Morquio syndrome, the specific GAG which builds up in the body is called keratan sulfate. This birth defect, which is autosomal recessive, is a type of lysosomal storage disorder. The buildup of GAGs in different parts of the body causes symptoms in many different organ systems. In the US, the incidence rate for Morquio syndrome is estimated at between 1 in 200,000 and 1 in 300,000 live births.
Enzyme replacement therapy (ERT) is a medical treatment which replaces an enzyme that is deficient or absent in the body. Usually, this is done by giving the patient an intravenous (IV) infusion of a solution containing the enzyme.
Hunter syndrome, or mucopolysaccharidosis type II, is a rare genetic disorder in which large sugar molecules called glycosaminoglycans build up in body tissues. It is a form of lysosomal storage disease. Hunter syndrome is caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S). The lack of this enzyme causes heparan sulfate and dermatan sulfate to accumulate in all body tissues. Hunter syndrome is the only MPS syndrome to exhibit X-linked recessive inheritance.
Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II, is part of the lysosomal storage disease family and results from a defective phosphotransferase. This enzyme transfers phosphate to mannose residues on specific proteins. Mannose-6-phosphate serves as a marker for proteins to be targeted to lysosomes within the cell. Without this marker, proteins are instead secreted outside the cell, which is the default pathway for proteins moving through the Golgi apparatus. Lysosomes cannot function without these proteins, which function as catabolic enzymes for the normal breakdown of substances in various tissues throughout the body. As a result, a buildup of these substances occurs within lysosomes because they cannot be degraded, resulting in the characteristic I-cells, or "inclusion cells" seen microscopically. In addition, the defective lysosomal enzymes normally found only within lysosomes are instead found in high concentrations in the blood, but they remain inactive at blood pH because they require the low lysosomal pH 5 to function.
An osteochondrodysplasia, or skeletal dysplasia, is a disorder of the development of bone and cartilage. Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia. Nonetheless, if taken collectively, genetic skeletal dysplasias or osteochondrodysplasias comprise a recognizable group of genetically determined disorders with generalized skeletal affection. These disorders lead to disproportionate short stature and bone abnormalities, particularly in the arms, legs, and spine. Skeletal dysplasia can result in marked functional limitation and even mortality.
Iduronidase, sold as Aldurazyme, is an enzyme with the systematic name glycosaminoglycan α-L-iduronohydrolase. It catalyses the hydrolysis of unsulfated α-L-iduronosidic linkages in dermatan sulfate.
Maroteaux–Lamy syndrome, or Mucopolysaccharidosis Type VI (MPS-VI), is an inherited disease caused by a deficiency in the enzyme arylsulfatase B (ARSB). ASRB is responsible for the breakdown of large sugar molecules called glycosaminoglycans. In particular, ARSB breaks down dermatan sulfate and chondroitin sulfate. Because people with MPS-VI lack the ability to break down these GAGs, these chemicals build up in the lysosomes of cells. MPS-VI is therefore a type of lysosomal storage disease.
Scheie syndrome is a disease caused by a deficiency in the enzyme iduronidase, leading to the buildup of glycosaminoglycans (GAGs) in the body. It is the most mild subtype of mucopolysaccharidosis type I; the most severe subtype of this disease is called Hurler Syndrome.
Hurler–Scheie syndrome is a genetic disorder caused by the buildup of glycosaminoglycans (GAGs) in various organ tissues. It is a cutaneous condition, also characterized by mild mental retardation and corneal clouding. Respiratory problems, sleep apnea, and heart disease may develop in adolescence.
Mucopolysaccharidosis type I is a spectrum of diseases in the mucopolysaccharidosis family. It results in the buildup of glycosaminoglycans due to a deficiency of alpha-L iduronidase, an enzyme responsible for the degradation of GAGs in lysosomes. Without this enzyme, a buildup of dermatan sulfate and heparan sulfate occurs in the body.
Emil Kakkis is an American medical geneticist known for his work to develop treatments for ultra rare disorders. He is the Founder of the Everylife Foundation for Rare Disease and Founder, CEO and President of Ultragenyx Pharmaceutical Inc.
Maria Luisa Escolar is a pediatrician, clinical professor, and researcher who specializes in pediatric neurodevelopmental disabilities. She is Founder and Director of the Program for the Study of Neurodevelopment in Rare Disorders at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center. Escolar is nationally and internationally known for her research and clinical care of children with leukodystrophies, lysosomal storage diseases, and other inherited metabolic diseases.
