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Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.
GRACILE syndrome is a rare genetic disorder that affects how the body processes energy, which may lead to serious and life-threatening health issues. The name GRACILE represents its main symptoms: growth retardation (slowed growth), aminoaciduria (high amount of amino acids in the urine), cholestasis (liver problems), iron overload (too much iron in the body), lactic acidosis (buildup of lactic acid), and early death.
This condition mainly affects babies and is primarily found in Finland, occurring in about 1 in 47,000 newborns. There have been over 30 documented cases in medical research. It’s important for families at risk to understand the genetic inheritance and symptoms, as the disorder can impact vital organs early in life.
GRACILE syndrome is a mitochondrial disorder, which means it affects the parts of cells responsible for producing energy. Genetic mutations in the BCS1L gene which is important for mitochondrial function cause this condition. When the mitochondria are unable to produce energy properly, it leads to significant complications throughout the body, especially affecting organs that require high energy, like the liver and kidneys.
Babies with GRACILE syndrome usually don’t show visible abnormalities at birth, but signs of the condition often start during pregnancy. They may experience slower growth in the womb, and after birth, they quickly develop various metabolic and liver-related issues. Without proper energy production, the body’s processes become disrupted, leading to a buildup of harmful substances like lactic acid and excess iron, further harming the body. GRACILE syndrome is a serious condition that may cause a lot of health problems. While doctors may provide treatments to help with some symptoms, the overall outlook for people with this syndrome is usually not very good.
The symptoms of GRACILE syndrome usually manifest early. Sometimes as soon as the prenatal stage. Most affected babies start showing signs of the condition in utero, with growth issues detectable via ultrasound. After birth, symptoms rapidly worsen due to the metabolic issues and organ dysfunctions caused by the condition.
Key symptoms include:
Symptoms of GRACILE syndrome may show up during pregnancy or shortly after birth. Understanding when these symptoms appear is important for accurate diagnosis and early intervention.Â
While symptoms may manifest at different ages, they mainly occur before birth or in the newborn period. This early onset highlights the need for prenatal screening and genetic testing for families at risk.
GRACILE syndrome is mainly caused by a change in the BCS1L gene’s DNA sequence. BCS1L gene helps create a protein needed to build the so-called complex III, which is part of the system that generates energy in our cells. This energy generation process is known as oxidative phosphorylation and is vital for keeping our bodies functioning properly.
Research studies have identified a specific mutation, S78G, in the BCS1L gene that causes GRACILE syndrome with markable iron overload in Finnish patients. Finnish patients had normal complex III activity and maintained normal energy production levels, suggesting that BCS1L may have additional roles in the body, particularly related to iron metabolism. Interestingly, some British babies with GRACILE syndrome had different mutations in the BCS1L gene, and they also experienced energy production issues. These findings highlight the importance of understanding how the BCS1L gene impacts both energy and iron metabolism and explains why individuals with GRACILE syndrome experience several specific health issues, such as liver problems and growth delays.
A more recent study indicates that mutations in the BCS1L gene may lead to a range of symptoms, such as a mild condition called Björnstad syndrome which is also a rare genetic condition characterized by two main features: hearing loss and a specific type of hair abnormality called “hair pili torti,” where the hair is twisted and fragile. People with this syndrome may also experience other symptoms, but the severity can vary widely. The study also reported on a 24-day-old boy who showed typical symptoms of GRACILE syndrome and had two new mutations in the BCS1L gene. He passed away at just five months old. These findings highlight the importance of accurate genetic testing, as pinpointing and understanding specific BCS1L mutations may lead to better diagnosis and treatment options for those affected by these syndromes.
Although GRACILE syndrome is hereditary, DNA mutations may also happen by chance during cell division or from outside influences like viruses or UV radiation. While these environmental factors do not directly cause GRACILE syndrome, they may play a role in how the syndrome manifests and its overall severity in affected individuals. Understanding these influences can help in managing the condition more effectively.
GRACILE syndrome is inherited in an autosomal recessive pattern. This means that a person needs to inherit two copies of the mutated gene. Typically, the parents of a child with GRACILE syndrome are considered “carriers.” They each have one mutated copy of the gene but do not show any symptoms because the second copy of the gene functions normally. However, if both parents pass their mutated copies to their child, that child will inherit the syndrome.
For families, it’s essential to know that if both parents are carriers, there is a 25% chance that each child will inherit GRACILE syndrome, a 50% chance of being a carrier like the parents, and a 25% chance of having two normal copies of the gene.Â
Genetic testing is important in diagnosing GRACILE syndrome. Identifying the specific mutations through genetic testing may help confirm the diagnosis of GRACILE syndrome early, often before symptoms become severe.Â
Genetic tests usually involve examining blood, saliva, or tissue samples to look for changes in the BCS1L gene. These tests may help identify mutations that may cause severe conditions like GRACILE syndrome.Â
Families with a history of GRACILE syndrome or those who have experienced unexplained health issues in infants are encouraged to consider genetic testing. This can help them understand their risk of having a child with the syndrome and allow them to take informed steps, such as seeking early monitoring or intervention if needed. Early diagnosis enables timely medical intervention and management, which can help improve outcomes for affected babies. This proactive approach can make a significant difference in their health and well-being.
There is currently no cure for GRACILE syndrome, there is only treatment which focuses on managing its symptoms and complications. Babies with this condition often need specialized medical care to address the key symptoms like lactic acidosis, aminoaciduria, cholestasis, and iron overload. Treatment may include dietary changes, medications, and regular check-ups to monitor organ function.
These are some management strategies that may help address its symptoms and improve the quality of life for affected individuals:
Genetic counseling is helpful for families dealing with GRACILE syndrome. As this condition is inherited in an autosomal recessive fashion,both parents need to carry the mutated gene for a child to be affected. A genetic counselor may help families understand their chances of having another child with the syndrome, explain how genetic testing works, and talk about various family planning options.Â
Counselors also provide emotional support and advice for managing the challenges of having a baby with a rare genetic disorder. For families thinking about future pregnancies, genetic counseling may help them make informed decisions and prepare them for what might happen.
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