Rare Pulmonology News

Disease Profile

GRACILE syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Antenatal

ICD-10

E88.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

FLNMS; Finnish lactic acidosis with hepatic hemosiderosis; Fellman syndrome;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Metabolic disorders

Summary

GRACILE syndrome is an inherited metabolic disease. GRACILE stands for growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death. Infants are very small at birth and quickly develop life-threatening complications. During the first days of life, infants will develop a buildup of lactic acid in the bloodstream (lactic acidosis) and amino acids in the urine (aminoaciduria). They will also have problems with the flow of bile from the liver (cholestasis) and too much iron in their blood. Affected individuals aren’t typically born with unique physical features. Although alkali therapy is used as treatment, about half of affected infants do not survive past the first days of life. Those that do survive this period generally do not live past 4 months despite receiving treatment. GRACILE syndrome is caused by a mutation in the BCS1L gene, and it is inherited in an autosomal recessive pattern. The BCS1L gene provides instructions needed by the mitochondria in cells to help produce energy.[1]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cholestasis
Slowed or blocked flow of bile from liver
0001396
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Decreased transferrin saturation
0012464
Elevated hepatic iron concentration
Increased iron concentration in liver
0012465
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hepatic steatosis
Fatty infiltration of liver
Fatty liver

[ more ]

0001397
Increased serum ferritin
Elevated serum ferritin
High ferritin level
Increased ferritin
Increased serum ferritin level

[ more ]

0003281
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Lactic acidosis
Increased lactate in body
0003128
Renal Fanconi syndrome
0001994
30%-79% of people have these symptoms
Death in early adulthood
0100613
1%-4% of people have these symptoms
Aminoaciduria
High urine amino acid levels
Increased levels of animo acids in urine

[ more ]

0003355
Neonatal hypotonia
Low muscle tone, in neonatal onset
0001319
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Chronic lactic acidosis
0004925
Increased serum iron
0003452
Increased serum pyruvate
0003542

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss GRACILE syndrome. Click on the link to view a sample search on this topic.

References

  1. Visapää I, Fellman V, Vesa J, et al. GRACILE Syndrome, a Lethal Metabolic Disorder with Iron Overload, Is Caused by a Point Mutation in BCS1L. Am J Hum Gen. 2002; 4:863-76. https://www.ncbi.nlm.nih.gov/pubmed/12215968. Accessed 7/23/2012.