Genetic Terms Glossary
View our Glossary of Genetic Terms. These terms are underlined throughout our website with a pink dotted line. Just hover off the words or terms for a quick definition.
Learn More about Genetic Conditions
We’re working to create easy-to-understand overviews for genetic conditions. Scroll down to Learn More.
Cystinosis is a genetic condition in which an amino acid called cystine builds up in the body’s cells as a result of changes or mutations in a gene called CTNS. Due to these CTNS gene mutations, people with cystinosis lack enough of an enzyme called cystinosin. Cystinosin works to help transport cystine out of the cells. If cystinosin doesn’t work correctly, then cystine will build up in the cells. As cystine builds up, it forms crystals that interrupt cell function leading to early cell death and organ damage. The kidneys, eyes and muscles are most significantly affected by the build up of cystine. The liver, muscles, pancreas, and brain are also commonly affected.
Three different forms of cystinosis have been identified: nephropathic cystinosis, which accounts for 95% of those affected, juvenile (intermediate) nephropathic cystinosis, which accounts for 3% of those affected, and non-nephropathic cystinosis which accounts for a very small number of those affected.All three forms of cystinosis are caused by changes, or mutations, in the CTNS gene. More than 100 different genetic changes in the CTNS gene have been identified. Specific gene changes may correlate with the symptoms of the disease as well as the overall severity and disease progression. Two important factors in determining the progression of the disorder are the age at diagnosis and the extent of disease symptoms and progression when treatment is first started.
Fabry Disease (FD)
Fabry disease is a progressive genetic condition that causes multiple health problems. Fabry disease occurs when a person’s body does not make enough of an enzyme called alpha-galactosidase A (alpha-Gal) due to changes or mutations in the GLA gene. When alpha-gal is not working, substances called glycolipids build up in the body’s lysosomes (the “recycling centers” of the cell). This storage leads to narrowed blood vessels, inflammation, and health problems all over the body, particularly in the skin, kidneys, heart, brain, intestines and nerves.
Fabry disease is commonly divided into two types, “classic” and “non-classic” or “later onset.” Both men and women can have classic and non-classic Fabry disease. The type of Fabry disease often determines the age symptoms start, the organs affected by the disease, how fast the disease progresses, and how severe symptoms become. Classic Fabry disease symptoms in males and females typically start in the first 2-10 years of life with the onset of burning pain in the hands and feet, decreased sweating, problems in the heat, a reddish-purplish rash, and gastrointestinal issues such as diarrhea, bloating, pain and constipation. Without treatment, the classic form of the disease progresses into kidney disease, heart disease, and increased stroke risk between the ages of 20 to 45. In non-classic Fabry disease, symptoms may start somewhat later in life and may more severely affect one organ like the heart or kidneys. In non-classic Fabry disease, heart disease and other symptoms still occur earlier than average in men than women so it is important to monitor the heart, kidneys, and brain from the time of diagnosis with Fabry disease. In both classic and non-classic Fabry disease, symptoms always worsen over time.
Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE) is a rare genetic disorder that causes repeated episodes of swelling similar to what is seen in an allergic reaction; however, unlike an allergic reaction, with HAE, there is usually no skin rash, hives, or itching. The swelling can occur anywhere but is most commonly seen in the face, hands, feet, eyelids, lips, tongue, and the lining of the gastrointestinal tract. Less often, swelling can also affect the throat or upper airways; these episodes can sometimes cause life-threatening complications. The symptoms of hereditary angioedema are highly variable-even within the same family. Some people may only have very few episodes or symptoms, while others have repeated, severe swelling attacks. Episodes usually last 2-5 days and go away on their own without treatment.
Like many rare disorders, hereditary angioedema (HAE) often goes unrecognized or misdiagnosed. Like many other rare diseases, the time it takes to receive an accurate diagnosis of HAE can take many years.
Hereditary Transthyretin (hATTR) Amyloidosis
Hereditary transthyretin (hATTR) amyloidosis is a rare genetic disorder. Amyloidosis is an “umbrella” term that describes a group of diseases in which specific proteins (called amyloid) build up in the body and clump together. hATTR amyloidosis is caused by a change (mutation) in the TTR gene. The resulting protein is misshapen and does not function correctly. The misfolded proteins form amyloid deposits that start to build up in the tissues and organs and will eventually cause irreversible damage. The nerves, heart, kidneys, and gastrointestinal tract are most commonly affected.
There are different forms of hereditary transthyretin amyloidosis (hATTR). How the disease affects one person can be very different from how it affects another person. The differences observed, such as the age of onset and severity of symptoms, can depend on the specific change in the TTR gene. The mutations observed in hATTR may be associated with specific symptoms or different forms of the condition.
hATTR amyloidosis with polyneuropathy is the most common form of the disorder. Affected individuals have problems with peripheral nerves (nerves outside of the central nervous system) and the autonomic nervous system, which controls involuntary actions of the body like sweating, blood pressure, and heart rate. Sometimes other symptoms can develop that affect the gastrointestinal system, the eyes, the heart, and the kidneys.
hATTR amyloidosis with cardiomyopathy predominantly affects the heart. This can cause heart enlargement, irregular heart rhythms (arrhythmias), chest pain, congestive heart failure, and sudden death. Neurological involvement is either absent or very mild.
Leptomeningeal transthyretin amyloidosis affects the central nervous system and the brain. People may have seizures, poor coordination (ataxia), stiffening of the muscles (spasticity), bleeding in the brain, psychosis, and dementia. This form of hATTR is extremely rare.