The GRACILE syndrome is a mitochondrial inherited disorder characterized by limited fetal growth, aminoaciduria, cholestasis, iron overload, lactacidosis and early death.
This syndrome is prevalent in Finland, which has an incidence of about 1/50,000 births. It has also been described in Turkish, and with a very low frequency, in Sweden and the United Kingdom.
It is an autosomal recessive inheritance.
The limitation appears early
fetal growth during pregnancy without signs of chronic hypoxia. Due to
the small fetal size, pregnancies tend to have premature births with low
weight at birth. The infant develops a fulminating lactic acidosis (pH
7.02 average; lactate 12.8 mmol/l) on the first day of life. In the
metabolic examination, it is found that the marked aminoaciduria is due
to Fanconi type tubulopathy. Iron overload is manifested with increased
plasma ferritin and decreased levels of transferrin, and an accumulation
of iron in the liver. Other signs of liver disease: cholestasis with
steatosis, fibrosis and cirrhosis.
No dysmorphic features have been detected and the only neurological abnormality described is an abnormal auditory response.
The GRACILE syndrome is caused
by mutations in the gene BCS1L, located on chromosome 2q35, and which
encodes a protein essential for the assembly of complex III in
mitochondrial respiratory chain.
In Finnish patients, the disease is caused by a homozygous mutation (c.232A>G) that causes an amino acid change serine to glycine at position 78 (p.Ser78Gly) in the BCS1L protein.
Other mitochondrial liver disease should be ruled out as Pearson syndrome. Mitochondrial disorders of fatty acid oxidation and Krebs cycle also can mimic GRACILE syndrome.
Treatments are symptomatic with poor prognosis.
GENE OR REGION STUDIED