GRACILE syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: FLNMS
Growth retardation, amino aciduria, cholestasis, iron overload, lactic acidosis, and early death
Finnish lethal neonatal metabolic syndrome
Growth restriction - aminoaciduria - cholestasis - iron overload - lactic acidosis - early death
Fellman syndrome
Lactic acidosis, Finnish, with hepatic hemosiderosis
Fellman disease
Growth delay - aminoaciduria - cholestasis - iron overload - lactic acidosis - early death
Number of Symptoms 29
OrphanetNr: 53693
OMIM Id: 603358
ICD-10:
UMLs: C1864002
MeSH: C537934
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 2 [Orphanet]
Inheritance: Autosomal recessive
Monogenic
12215968 [IBIS]
Age of onset: Neonatal
Infancy
12215968 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Mitochondrial disorder due to a defect in assembly or maturation of the respiratory chain complexes
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death) syndrome is a recessively inherited lethal disease characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. It is caused by mutations in the BCS1L gene (= BCS, BCS1, BJS, FLNMS, GRACILE, Hs.6719, MC3DN1, PTD, h-BCS, h-BCS1). BCS1L, encodes a mitochondrial protein that functions as a chaperone in the assembly of complex III (cytochrome bc1 complex) of the mitochondrial respiratory chain (PMID:12215968).

Symptom Information: Sort by abundance 

1
 (HPO:0004925) Chronic lactic acidosis 12215968 IBIS 3 / 7739
2
 (HPO:0002151) Increased serum lactate 12215968 IBIS 92 / 7739
3
 (HPO:0003128) Lactic acidosis Very frequent [IBIS] 12215968 IBIS 116 / 7739
4
 (HPO:0004325) Decreased body weight Very frequent [IBIS] Very frequent [Orphanet] 100% (n=17) 12215968 IBIS 492 / 7739
5
 (HPO:0001943) Hypoglycemia 22970607 IBIS 131 / 7739
6
 (HPO:0003542) Increased serum pyruvate 12215968 IBIS 18 / 7739
7
 (HPO:0004337) Abnormality of amino acid metabolism Very frequent [IBIS] Very frequent [Orphanet] 12215968 IBIS 45 / 7739
8
 (HPO:0003355) Aminoaciduria Very frequent [IBIS] 20/20 [HPO:probinson] 100% (n=17) 12215968 IBIS 65 / 7739
9
 (HPO:0008972) Decreased activity of mitochondrial respiratory chain 12215968 IBIS 34 / 7739
10
 (HPO:0011924) Decreased activity of mitochondrial complex III 12215968 IBIS 22 / 7739
11
 (HPO:0011031) Abnormality of iron homeostasis Very frequent [IBIS] Very frequent [Orphanet] 12215968 IBIS 16 / 7739
12
 (HPO:0012463) Elevated transferrin saturation 12215968 IBIS 10 / 7739
13
 (HPO:0003281) Increased serum ferritin Very frequent [IBIS] 12215968 IBIS 32 / 7739
14
 (HPO:0003452) Increased serum iron 12215968 IBIS 5 / 7739
15
 (HPO:0001252) Muscular hypotonia 12215968 IBIS 990 / 7739
16
 (HPO:0001319) Neonatal hypotonia 3/20 [HPO:probinson] 12215968 IBIS 101 / 7739
17
 (HPO:0001298) Encephalopathy 12215968 IBIS 72 / 7739
18
 (HPO:0001250) Seizures 12215968 IBIS 1245 / 7739
19
 (HPO:0001511) Intrauterine growth retardation Very frequent [IBIS] 100% (n=17) 12215968 IBIS 358 / 7739
20
 (HPO:0003777) Pili torti 20580947 IBIS 24 / 7739
21
 (HPO:0001396) Cholestasis Very frequent [IBIS] Very frequent [Orphanet] 19/20 [HPO:probinson] 100% (n=17) 12215968 IBIS 136 / 7739
22
 (HPO:0001394) Cirrhosis Very frequent [Orphanet] 20580947 IBIS 102 / 7739
23
 (HPO:0000124) Renal tubular dysfunction Very frequent [Orphanet] 12215968 IBIS 46 / 7739
24
 (HPO:0000365) Hearing impairment Very frequent [Orphanet] 20580947 IBIS 539 / 7739
25
 (HPO:0040134) Abnormal hepatic iron concentration 12215968 IBIS 1 / 7739
26
 (HPO:0001522) Death in infancy Very frequent [IBIS] Frequent [Orphanet] 12215968 IBIS 275 / 7739
27
 (OMIM) Hepatic hemosiderosis 12215968 IBIS 2 / 7739
28
 (OMIM) Leigh syndrome 12215968 IBIS 7 / 7739
29
 (OMIM) Renal tubulopathy 12215968 IBIS 4 / 7739

Associated genes:

BCS1L;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Fellman et al. (1998) described a neonatal metabolic disorder characterized by severe intrauterine growth retardation, fulminant lactic acidosis during the first days of life, Fanconi-type amino aciduria, and abnormalities in iron metabolism, including liver hemosiderosis. Affected infants failed ...
Molecular genetics OMIM In Finnish patients with GRACILE syndrome, Visapaa et al. (2002) identified a homozygous mutation in the BCS1L gene that resulted in a ser78-to-gly (S78G; 603647.0005) substitution. They also identified 5 different mutations in the BCS1L gene in 3 ...
Population genetics OMIM Because GRACILE syndrome had not been described elsewhere in the world, Fellman et al. (1998) presumed that it represented a new member of the Finnish disease heritage, a group of 30 rare monogenic disorders enriched or encountered only ...