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GRACILE syndrome is a severe disorder that begins before birth. GRACILE stands for the condition's characteristic features: growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death.
In GRACILE syndrome, growth before birth is slow (intrauterine growth retardation). Affected newborns are smaller than average and have an inability to grow and gain weight at the expected rate (failure to thrive). A characteristic of GRACILE syndrome is excess iron in the liver, which likely begins before birth. Iron levels may begin to improve after birth, although they typically remain elevated. Within the first day of life, infants with GRACILE syndrome have a buildup of a chemical called lactic acid in the body (lactic acidosis). They also have kidney problems that lead to an excess of molecules called amino acids in the urine (aminoaciduria). Babies with GRACILE syndrome have cholestasis, which is a reduced ability to produce and release a digestive fluid called bile. Cholestasis leads to irreversible liver disease (cirrhosis) in the first few months of life.
Because of the severe health problems caused by GRACILE syndrome, infants with this condition do not survive for more than a few months, and about half die within a few days of birth.
GRACILE syndrome is found almost exclusively in Finland, where it is estimated to affect 1 in 47,000 infants. At least 32 affected infants have been described in the medical literature.
GRACILE syndrome is caused by a mutation in the BCS1L gene. The protein produced from this gene is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. In mitochondria, the BCS1L protein plays a role in oxidative phosphorylation, which is a multistep process through which cells derive much of their energy. The BCS1L protein is critical for the formation of a group of proteins known as complex III, which is one of several protein complexes involved in oxidative phosphorylation.
The genetic change involved in GRACILE syndrome alters the BCS1L protein, and the abnormal protein is broken down more quickly than the normal protein. What little protein remains is able to help form some complete complex III, although the amount is severely reduced, particularly in the liver and kidneys. As a result, complex III activity and oxidative phosphorylation are decreased in these organs in people with GRACILE syndrome. Without energy, these organs become damaged, leading to many of the features of GRACILE syndrome. It is not clear why a change in the BCS1L gene leads to iron accumulation in people with this condition.
Changes in this gene are associated with GRACILE syndrome.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
These resources address the diagnosis or management of GRACILE syndrome and may include treatment providers.
You might also find information on the diagnosis or management of GRACILE syndrome in Educational resources and Patient support.
General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).
To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
You may find the following resources about GRACILE syndrome helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
Ask the Genetic and Rare Diseases Information Center (https://rarediseases.info.nih.gov/gard).
acidosis ; acids ; aciduria ; autosomal ; autosomal recessive ; bile ; cell ; cirrhosis ; digestive ; failure to thrive ; gene ; hepatic ; inherited ; intrauterine growth retardation ; iron ; kidney ; lactic acid ; lactic acidosis ; mitochondria ; mutation ; neonatal ; oxidative phosphorylation ; phosphorylation ; protein ; recessive ; syndrome
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.