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Signs and Symptoms
GRACILE syndrome is a genetic metabolic disorder that principally occurs in Finland. It is thought to be a consequence of a genetic effect called the founder-effect. This means that remote, small populations, for example those founding new colonies, have a higher prevalence of recessive disorders. The name GRACILE is an acronym denoting the symptoms of this disease:
- Growth Retardation
- Aminoaciduria: the presence of amino acids in the urine.
- Cholestasis: a condition where the bile cannot flow from the liver to the duodenum.
- Iron overload
- Lactic acidosis: characterized by a low pH (meaning more acidic) in body tissues and blood, accompanied by the accumulation of lactate.
- Early death
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Genetics of GRACILE Syndrome
This syndrome is an autosomal recessive condition caused by a homozygous missense mutation in the BCS1L gene known by the name S78G. This means that the amino acid serine on position 78 is changed into glycine. This gene normally codes for a mitochondrial protein that chaperones the assembly of the mitochondrial respiratory chain complex III, a complex of molecules in the electron transport chain. This chain is, among others, responsible for the biochemical generation of ATP.
A very rare similar mutation in this gene has been found in British and Turkish infants. This mutation leads to symptoms comparable to those exhibited by infants suffering from GRACILE syndrome.
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Prevalence and Prognosis
The estimates that are available are only applicable to Finland, since the condition is most prevalent and thus most studied there. The estimated incidence of GRACILE syndrome in Finland is 1 in every 47,000 to 70,000 births.
As the name indicates, the syndrome leads to an early death. Most affected infants die before they reach the age of five months, with a median survival of seven days.
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At present, there is no cure for this condition. Treatment focuses on pain prevention and other supportive measures. Often an infusion of apotransferrin is applied, followed by an exchange transfusion. This clears the blood plasma of non-transferrin-bound iron and decreased transferrin saturation. This treatment, however, is not able to prevent an early death.
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- Barton, J.C.; Edwards, C.Q.; Phatak, P.D.; Britton, R.S. & Bacon, B.R. (2010). Handbook of Iron Overload Disorders. Cambridge University Press
- Fellman, V. (2002). The GRACILE Syndrome, a Neonatal Lethal Metabolic Disorder with Iron Overload. Blood Cells, Molecules and Diseases. 29(3), 444 – 450.
- John Hopkins University, Online Mendelian Inheritance in Man: http://www.ncbi.nlm.nih.gov/omim/603358
- Lund University, Medical Faculty: http://www.research.med.lu.se/en_projektdetaljer.php?Proj=536
- Vispää, I.; Fellman, V.; Vesa, J.; Dasvarma, A.; Hutton, J.L.; Kumar, V.; Payne, G.S.; Makarow, M.; Van Coster, R.; Taylor, R.W.; Turnbull, D.M.; Suomalainen, A. & Peltonen, L. (2002). GRACILE Syndrome, a Lethal Metabolic Disorder with Iron Overload, Is Caused by a Point Mutation in BCS1L. The American Society of Human Genetics. 71(4), 863 – 876.