Genes contain the information on how our body functions. We have 2 sets of genes - one set from each parent. When the information in the genes changes, this can affect how they work and can lead to a number of different diseases. There are over 400 inborn errors of metabolism that give rise to metabolic diseases.
Looking for which mutation is causing metabolic diseases by checking each of the suspected genes has not been possible with older technology. Newer technology now exists to look at the genes, which is called next generation sequencing. By focusing on the genes that have been shown previously to cause human disease, a targeting next generation sequencing panel can be performed in a shorter period of time than sequencing every gene.
Biomedical research in rare genetic and metabolic diseases has yielded a number of treatments. Learn more about some of the metabolic diseases and available drugs prescribed for them:
Fabry disease is an inherited disorder that results from the buildup of a particular type of fat, called globotriaosylceramide, in the body's cells. Beginning in childhood, this buildup causes signs and symptoms that affect many parts of the body. Characteristic features of Fabry disease include episodes of pain, particularly in the hands and feet (acroparesthesias); clusters of small, dark red spots on the skin called angiokeratomas; a decreased ability to sweat (hypohidrosis); cloudineses of the front part of the eye (corneal opacity); problems with the gastrointestinal system; ringing in the ears (tinnitus); and hearing loss. Some affected individuals have milder forms of the disorder that appear later in life and affect only the heart or kidneys.
Drugs: Replagal (algalsidase alpha), Fabrazyme (algalsidase beta), Gene Therapy.
Pompe disease is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, imparis their ability to function normally. Researchers have described three types of Pompe disease, which differ in severity and the age at which they appear. These types are known as classic infantile-onset, non-classic infantile-onset, and late-onset. The classic form of infantile-onset Pompe disease begins within a few months of birth. Infants with this disorder typically experience muscle weakness (myopathy), poor muscle tone (hypotonia), an enlarged liver (hepatomegaly), and heart defects. The non-classic form of infantile-onset Pompe disease usually appears by age 1. It is characterized by delayed motor skills (such as rolling over and sitting) and progressive muscle weakness. The late-onset type of Pompe disease may not become apparent until later in childhood, adolescence, or adulthood. Late-onset Pompe disease is usually milder than the infantile-onset forms of this disorder and is less likely to involve the heart.
Drugs: Myozyme (alglucosidase alfa)
Hypophosphatasia is an inherited disorder that affects the development of bones and teeth. This condition disrupts a process called mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding. The signs and symptoms of hypophosphatasia vary widely and can appear anywhere from before birth to adulthood. The most severe forms of the disorder tend to occur before birth and in early infancy. The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy.
Drugs: Strensiq (asfotase alfa)
Mycopolysaccharidosis type II (MPSII), also known as Hunter syndrome, is a condition that affects many different parts of the body and occurs almost exclusively in males. It is a progressively debilitating disorder; however, the rate of progression varies among affected individuals. At birth, individuals with MPS II do not display any features of the condition. Between ages 2 and 4, they develop full lips, large rounded cheeks, a broad nose, and an enlarged tongue (macroglossia). The vocal cords also enlarge, which results in a deep, hoarse voice. Many other organs and tissues are affected in MPS II. Individuals with this disorder often have a large head (macrocephaly), a buildup of fluid in the brain hydrocephalus), an enlarged liver and spleen (hepatosplenomegaly), and a soft out-pouching around the belly-button (umbilica hernia) or lower abdomen (inguinal hernia). People with MPS II usually have thick skin that is not very stretchy. Children with MPS II grow steadily until about age 5, and then their growth slows and they develop short stature. Individuals with this condition have joint deformities (contractures) that significantly affect mobility.
Drugs: Elaprase (idursulfase)
Mucopolysaccharidosis type IV (MPS IV), also known as Morquio syndrome, is a progressive condition that mainly affects the skeleton. The rate at which symptoms worsen varies among affected individuals. The first signs and symptoms of MPS IV usually become apparent during early childhood. Affected individuals develop various skeletal abnormalities, including short stature, knock knees, and abnormalities of the ribs, chest, spine, hips, and wrists. People with MPS IV often have joints that are loose and very flexible (hypermobile), but they may also have restricted movement in certain joints. A characteristic feature of this condition is underdevelopment (hypoplasia) of a peg-like bone in the neck called the odontoid process. In people with MPS IV, the clear covering of the eye (cornea) typically becomes cloudy, which can cause vision loss. The life expentancy of individuals with MPS IV depends on the severity of symptoms.
Drugs: Vimizim (elsosulfase alpha)
Drugs: Naglazyme (galsulfase)
A urea cycle disorder is a genetic disorder resulting in a deficiency of one of the six enzymes in the urea cycle. These enzymes are responsible for removing ammonia from the blood stream. In urea cycle disorders, the nitrogen accumulates in the form of ammonia, a highly toxic substance, resulting in hyperammonemia (elevated blood ammonia). Ammonia then reaches the brain through the blood, where it can cause irreversible brain damage. The onset and severity of urea cycle disorders is highly variable. This depends on the specific mutation involved and correlates with the amount of urea cycle enzyme function. Children with severe urea cycle disorders typically show symptoms after the first 24 hours of life, including seizures, hypotonia (poor muscle tone), respiratory distress (respiratory alkalosis), and coma. Children with mild or moderate urea cycle enzyme deficiencies may not show recognizable symptoms until early childhood.
Drugs: Pheburane (sodium phenylbutyrate), Ravicti (glycerol phenylbutyrate), Gene Therapy
Mitochondrial disease refers to a group of diseases involving a problem with mitochondria. There are many types of mitochondrial disease, and many have yet to be discovered. When mitochondria fail, less energy is converted in the cells. The cells may stop working or die. Depending on where the affected cells are, parts of the body may not function properly and many health problems can result. The symptoms of mitochondrial disease can range from mild to severe. People with mitochondrial disease often have one or more of these symptoms: developmental delay or regression in development, seizures, strokes, muscle weakness, muscle cramps, poor muscle tone (hypotonia), tremors, poor balance (ataxia), deafness, loss of vision or blindness, and heart, liver or kidney disease at a young age.
Drugs: Currently treatment is focused on alleviating symptoms and slowing down progression of the disease, due to the wide variety of diseases.