Gracile syndrome

Some genetic conditions, like GRACILE syndrome, are found only in certain groups of people because they share common ancestors, meaning they come from the same very distant relatives. Because of sharing distant relatives, these people share more gene changes with each other than they do with other people in the world. One of these common relatives must have had a change in the BSC1L gene that was then passed down through many generations to some of the members of the Finnish population who are alive today. This is called a “founder effect”. People can learn more about founder affects in GRACILE syndrome by talking to a genetic counselor. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

Blood relatives of a person with GRACILE syndrome all have a chance of being a carrier for the condition. Siblings (who do not have symptoms of GRACILE syndrome) have a 2 in 3, or about 66%, chance of being a carrier for GRACILE syndrome. Parents of a person with GRACILE syndrome must be carriers. More distant relatives of the individual have different chances of being carriers: aunts/uncles have a 50% chance, each grandparent has a 25% chance, and cousins have a 25% chance. Families can talk to a genetic counselor to find out who in the family should be tested for GRACILE syndrome. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

Since GRACILE syndrome is very rare, it may be difficult to find other families affected by the condition. You may want to start by looking in the discussion community for GRACILE syndrome organized by Rare Share. You can also try looking at the Society for Inherited Metabolic Disorders and the National Information Centre for Metabolic Diseases. Finally, you can try to ask the doctors involved in your child’s care to see if they know any other families with the condition.

One of the first symptoms of GRACILE syndrome is fetal growth restriction, which means that the baby is smaller than typical before it is born. This is usually the first symptom that is noticed in people with GRACILE syndrome. After the baby is born, it develops lactic acidosis (too much lactic acid in the body), aminoaciduria (amino acids in the urine due to kidney damage), and liver damage. Parents of children with GRACILE syndrome can talk to a medical geneticist or other neonatal specialist to learn more about the symptoms of GRACILE syndrome in the neonatal period. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

Infants with GRACILE syndrome will need a team of specialist to help treat them. This may include neonatologist, nephrologist, gastroenterologist, and geneticist. People can talk to their primary doctor to find the best treatment options.

Infants with GRACILE syndrome usually pass away within the first few days to months of their lives. This is usually due to their body not having enough energy to keep working the way it is supposed to. The liver and kidneys are especially affected by the low levels of energy and the damage to these organs is very serious. Parents can talk to their infant’s care team to learn more about their child’s case.

Unfortunately there are not very many treatment options available for infants with GRACILE syndrome. Some doctors may treat infants with alkali therapy, a treatment to try to change the blood pH level. Most treatment for GRACILE syndrome is called palliative care, or care designed to make the infant comfortable and not to cure the disease. People can talk with a medical geneticist or a neonatal specialist about the treatment options for GRACILE syndrome in the neonatal period. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

It is estimated that about 1 in 120 people in Finland are carriers for GRACILE syndrome. People can find out more about the frequency of BCS1L mutations in Finland by speaking with a genetic counselor. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

GRACILE syndrome is a type of genetic disease known as a metabolic disease. This means that GRACILE syndrome affects the way the body makes energy. It is caused by a change (sometimes called a mutation) in the BSC1L gene and is inherited in an autosomal recessive manner. Almost all cases of GRACILE syndrome have occurred in Finland. “GRACILE” stands for growth retardation (GR), aminoaciduria (A), cholestasis (C), iron overload (I), lactic acidosis (L), and early death (E). Babies with this condition are born much smaller than usual, have kidney and liver damage, and have too much lactic acid and iron in their blood. Most infants with GRACILE syndrome pass away after a few days, but they may live for a few months. Unfortunately, there is no cure for GRACILE syndrome. Usually, a medical geneticist or other neonatal specialist will diagnose GRACILE syndrome in the neonatal period. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

GRACILE syndrome mainly affects the liver and the kidneys of infants with the condition. It can also cause hearing impairment and low muscle tone (hypotonia). Parents can talk with a medical geneticist about what symptoms to expect in GRACILE syndrome. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

Changes in the BSC1L gene change the way the BSC1L protein works. This protein is very important in the mitochondria, the energy factories of the cell. When changes in BSC1L happen, the protein breaks down and is taken away from the cell more quickly. This means there is not enough BSC1L in the cell to make the energy our body needs. Since there is still some BSC1L in the cell, it can still make a little bit of energy. Some body parts are more affected by this than others, especially the liver and the kidneys. Without enough energy, these organs cannot work as well as they usually do and they become damaged. This damage is what causes many of the symptoms of GRACILE syndrome. Patients can speak with a physician with special training in treating metabolic disease such as a medical geneticist to find out more about the changes in the BSC1L gene cause the symptoms of GRACILE syndrome. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

GRACILE syndrome is caused by a change or "mutation" in the BCS1L gene. The most common change in this gene that has been seen in people with GRACILE syndrome is called the c.232A>G mutation. This means at position number 232, there is a G in the DNA where people should have an A. Specially trained healthcare providers called genetic counselors can explain more about specific genetic changes in the BCS1L gene. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

The BCS1L gene gives the instructions to make a protein called BSC1L. This protein is found in the mitochondria, which is like a factory for energy in the cell. The BSC1L protein is like a piece of machinery in the factory. BSC1L is an important part of the the way our body uses oxygen to make energy for our body. The process of making oxygen into energy is called oxidative phosphorylation. The BSC1L protein is part of the third complex in oxidative phosphorylation.

Certain changes in the BSC1L gene can stop the body from making BSC1L protein. If there is not enough BSC1L protein, the oxidative phosphorylation machine can no longer work. If oxidative phosphorylation doesn’t work, the body’s cells cannot make enough energy. If cells do not have enough energy, this can cause damage to the body’s organs. This damage is what causes the symptoms of GRACILE syndrome.
To understand more about the job of the BSC1L gene, patients can go to the GRACILE syndrome page on Genetics Home Reference.

Everyone has different changes in their genes. That’s what makes us all different! A variant is a change that has never been seen before or is not understood very well. If you have inherited a variant in BSC1L, it means that your BSC1L gene is a little different than other people, but that we don’t yet know if this difference makes the gene work less or if the gene works normally.

Since GRACILE syndrome is caused by changes in both of a person’s BSC1L genes, it is possible to see someone who has one change that we do not yet understand and one change that we know makes the BSC1L gene work less. It is also possible to see someone with 2 changes that we do not yet understand. If this person is having symptoms of GRACILE syndrome, it makes it more likely that the changes make the gene work less. If the person is not having symptoms, it makes it more likely that the changes are harmless.
Understanding how diseases are inherited can be complicated. People can find out more about autosomal recessive inheritance by visiting the National Library of Medicine or by talking to a genetic counselor. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

GRACILE is an acronym for the most common features of GRACILE syndrome: Growth Retardation, Aminoaciduria, Cholestasis, Iron overload, Lactic acidosis, and Early death. Talking to a doctor who specializes in caring for newborns (called a neonatologist) can help parents understand the different features of GRACILE syndrome.

The first steps after a diagnosis of GRACILE syndrome are to speak with a physician about treatment options. People can talk with a medical geneticist or a neonatal specialist about the treatment options for GRACILE syndrome in the neonatal period. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

The most common features of GRACILE syndrome are:

GRACILE syndrome is not included on the newborn screen in the United States. The newborn screen is a blood test that all babies born in a hospital have in the first few days after birth. If a doctor suspects that an infant may have GRACILE syndrome, he or she will do genetic testing on the BSC1L gene to confirm the diagnosis. Patients can find out more about genetic testing of the BSC1L gene by going to the Genetic Testing Registry website or by talking to a genetic counselor. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

There are a few different kinds of genetic tests available that can find different types of genetic changes in the BSC1L gene:

As of 05/10/2016, there are no open research studies going on for GRACILE syndrome. People can check www.clinicaltrials.gov for the latest status.

GRACILE syndrome is characterized by the six symptoms that form its name: growth retardation (GR), aminoacidosis (A), cholestasis (C), iron overload (I), lactic acidosis (L), and early death (E). Parents can talk with a medical geneticist about the characteristic symptoms of GRACILE syndrome. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

Changes in the BCS1L gene cause GRACILE syndrome and other disorders related to this gene. Patients can talk with a genetic counselor to find out more about the cause of GRACILE syndrome. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

If a family has a previous case of GRACILE syndrome and a change in the BSC1L gene is already known, prenatal testing can be done to see if the baby has GRACILE syndrome or not. This can be done by a chorionic villus sampling (CVS), which takes a sample of the placenta for testing, or an amniocentesis, which takes a sample of the fluid around the baby for the testing.
People can find out more about prenatal testing for GRACILE syndrome by talking to a genetic counselor. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

Almost all babies born with GRACILE syndrome are born in Finland. A few cases have been reported in Sweden and the United Kingdom. A genetic counselor can help patients understand how common GRACILE syndrome is in a particular population. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

It is difficult to know exactly how many babies have been born with GRACILE syndrome since they might not all be reported in medical books and articles. However, at least 32 babies with GRACILE syndrome have been reported before. To find out more about how many cases of GRACILE syndrome have been reported, patients can speak with a genetic counselor. A genetic counselor can help understand how common GRACILE syndrome is in a particular population. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

Babies with GRACILE syndrome have many severe symptoms that affect many parts of the baby’s body. Unfortunately, this means babies with GRACILE syndrome do not live for very long after birth. About half of babies born with GRACILE syndrome pass away within the first few days after birth, and the others pass away within the first few months. Parents can talk to their infant’s care team to learn more about how long their baby might live.

Testing for GRACILE syndrome usually happens right after birth. Doctors may order a blood test for babies that are born small. Babies with GRACILE syndrome will have a high iron level and a build up of lactic acid in their blood. This is called lactic acidosis. Doctors may also test the baby’s urine for protein building blocks called amino acids. A high level of amino acids in the urine is called aminoaciduria. If a doctor suspects that a baby has GRACILE syndrome, he or she can order genetic testing of the BCS1L gene to know for sure. Usually, a medical geneticist or other neonatal specialist will diagnose GRACILE syndrome in the neonatal period. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

We each typically have 2 copies of the BSC1L gene, one from our mother and one from our father. We only need 1 copy of the BSC1L gene to work in order for our cells to work properly. In order to have GRACILE syndrome, both copies of the BSC1L gene need to have changes or mutations that make the gene not work properly. This is called autosomal recessive inheritance. The changes in the two copies of the BSC1L gene can be the same change or different. As long as both changes make the gene work less or not at all, the person will have GRACILE syndrome. Someone who only has 1 change is known as a carrier. Therefore, the parents of a person with GRACILE syndrome are both carriers of a change in the BSC1L gene. Parents can talk to a genetic counselor to learn more about how GRACILE syndrome is inherited. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

Doctors suspect GRACILE syndrome when a baby is born much smaller than he/she should be, has hypoglycemia (low blood sugar), lactic acidosis (high levels of lactic acid), increased iron levels, and liver damage. Usually, a medical geneticist or other neonatal specialist will diagnose GRACILE syndrome in the neonatal period. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

To help support GRACILE syndrome research, you can donate to:

Visit www.clinicaltrials.gov or trialsfinder.org to look for clinical research for GRACILE syndrome.

Because GRACILE syndrome is so rare, there are few doctors in the world who have experience treating the condition. To find a doctor familiar with the condition, you may try searching the medical literature for recent articles on GRACILE syndrome and contacting the authors of the paper. They may be able to help you find someone familiar with the condition. Otherwise, you may want to try contacting an academic health care center (usually associated with a university) local to you. Academic health care centers tend to have the most up to date technology and may be involved in clinical research. People can search the American College of Medical Genetics Clinic Services Search Engine to find a genetics provider.

GRACILE syndrome is a very rare condition in the general population. Overall, it occurs in much less than 1 in 1 million people across the world. However, almost all cases of GRACILE syndrome have happened in Finland. Therefore, in Finland, about 1 in 47,000 babies are born with GRACILE syndrome. A genetic counselor can help patients understand how common GRACILE syndrome is in a particular population. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

Most of the genetic testing laboratories who perform the testing on the BSC1L gene will accept blood and saliva as samples for genetic testing. There is no need to perform a biopsy for testing. Testing can also be done on prenatal samples like chorionic villus sample (from CVS) or amniotic fluid (from amniocentesis). People can find out more about genetic testing of the BSC1L gene by going to the Genetic Testing Registry website or by talking to a genetic counselor. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

So far, all patients reported with GRACILE syndrome have had the same change in BSC1L, known as c.232A>G. This means that at position number 232 in the DNA, there is a G where people usually have an A. Patients can find out the specific change in BSC1L by doing a blood test on their DNA. A medical geneticist or a genetic counselor can help find out what change in the BSC1L a patient may have. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

There is nothing that makes GRACILE syndrome worse. Having a child with GRACILE syndrome is not the fault of the parents and is not due to something Mom or Dad did or did not do during pregnancy. There is nothing a parent could eat, drink, or do during their pregnancy to cause GRACILE syndrome or to prevent it. Parents can talk with a doctor who specializes in caring for newborns called a neonatologist to understand more about the symptoms of GRACILE syndrome. Parents can also speak with a genetic counselor to discuss causes of GRACILE syndrome. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

Many other metabolic disease can have similar symptoms as GRACILE syndrome. It is important for a doctor to rule out other disease that affect the mitochondria, the energy factory of the cell. One disease that is similar to GRACILE syndrome is called Pearson syndrome. Parents can speak with their child’s doctor or a medical geneticist to make sure all similar diseases have been tested for when diagnosing GRACILE syndrome.

Male and female babies have the same chance of having GRACILE syndrome. People can find out more about the chances of having GRACILE syndrome by speaking with a genetic counselor. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

Unfortunately, there is no cure for GRACILE syndrome. The treatments used for GRACILE syndrome are meant to make infants more comfortable. Most infants born with GRACILE syndrome do not survive the first few days of life. People can talk with a medical geneticist or a neonatal specialist about the treatment options for GRACILE syndrome in the neonatal period. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

Some changes in BSC1L can cause diseases other than GRACILE syndrome. One of these conditions looks a lot like GRACILE syndrome but only affects the liver and kidneys. It is possible for these other conditions develop later on in infancy or in childhood. Some of these conditions can cause swelling in the brain and even psychiatric disorders. Finally, a milder condition called Bjornstad syndrome can be caused by changes in the BSC1L gene. Patients can talk to a genetic counselor about the other disease caused by the BSC1L gene. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.

The only treatments available for GRACILE syndrome are to manage the symptoms for some time. Babies with the condition are treated in the intensive care unit (ICU) of the hospital. The may be given medicines to try to decrease the amount of lactic acid in their bodies, but it only works slightly. People can talk with a medical geneticist or a neonatal specialist about the treatment options for GRACILE syndrome in the neonatal period. To find a medical geneticist, patients can search the American College of Medical Geneticists "Find a Member" site.

There are a few other names people might use when talking about GRACILE syndrome:

GRACILE syndrome is a very rare condition, so support resources are not very common either. Rare Share has a discussion community for GRACILE syndrome, but it currently has no members. There are support resources for patients and families affected by metabolic diseases, including:

All known forms of GRACILE syndrome are genetic. People can learn more about the causes of GRACILE syndrome by talking to a genetic counselor. A genetic counselor can be found through the "Find a Genetic Counselor" link on the National Society of Genetic Counselors website.