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Gracile syndrome (GRACILE)

Genes

  • Bcs1 homolog, ubiquinol-cytochrome c reductase complex chaperone (BCS1L)

Summary

The name for GRACILE syndrome comes from the main clinical manifestations of this fatal disease of newborn: Growth Retardation Aminoaciduria Cholestasis Iron overload Lactic acidosis Early death The disease is caused by mutations in BCS1L gene. The gene product of BCS1L gene is a mitochondrial inner membrane protein but the pathogenetic mechanisms involved in the Gracile syndrome are still unknown. The disorder already begins in utero as shown by extremely low birth weight with an average of 1700 g (-3.8 SD of gestational age). No dysmorphic features are present in the newborns who during the first day develope severe lactic acidosis with arterial pH value averaging 7,0. Despite alkalising therapy half of the patients die during the first two days and the rest of them during the following one to four months wihout any major neurological symptoms. Autopsy studies have revealed cholestasis in liver and extensive amounts of iron in hepatocytes and Kupffer cells. Non-specific aminoaciduria is a constant finding in GRACILE syndrome. The clinical diagnosis of GRACILE syndrome can be supported by gene test of the founder mutation.

Links

UMLS Concept names

  • C1864002 FLNMS
  • C1864002 GRACILE SYNDROME
  • C1864002 FELLMAN SYNDROME
  • C1864002 FINNISH LETHAL NEONATAL METABOLIC SYNDROME
  • C1864002 GROWTH RETARDATION, AMINO ACIDURIA, CHOLESTASIS, IRON OVERLOAD, LACTIC ACIDOSIS, AND EARLY DEATH
  • C1864002 LACTIC ACIDOSIS, FINNISH, WITH HEPATIC HEMOSIDEROSIS

Selected publications

  • Am J Hum Genet. 2002 Oct;71(4):863-76. Epub 2002 Sep 5. GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused by a point mutation in BCS1L. Visapää I1, Fellman V, Vesa J, Dasvarma A, Hutton JL, Kumar V, Payne GS, Makarow M, Van Coster R, Taylor RW, Turnbull DM, Suomalainen A, Peltonen L. PMID: 12215968 (Pubmed)