Arterial calcification, generalized, of infancy, 1

General Information (adopted from Orphanet):

Synonyms, Signs: GACI1
IIAC
GACI
Arterial calcification, idiopathic infantile
Arteriopathy, occlusive infantile coronary sclerosis, medial, of infancy, included
Idiopathic infantile arterial calcification
Number of Symptoms 52
OrphanetNr:
OMIM Id: 208000
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
30005391 [IBIS]
Age of onset: Antenatal, Neonatal, Infancy
29976176 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT

Comment:

Cutaneous features of pseudoxanthoma elasticum were found in a patient with generalized arterial calcification of infancy due to a homozygous missense mutation in the ENPP1 gene. No pathogenetic mutations were found in the ABCC6 or MGP genes (PMID:22229486). Inactivating mutations in ENPP1 have previously been described to cause generalized arterial calcification of infancy (GACI). That both GACI and hypophosphatemic rickets are caused by loss-of-function mutations is most strongly supported by the observation of a single family, in which the father has hypophosphatemic rickets whereas his son is affected by severe GACI plus hypophosphatemia, although both carry the same homozygous ENPP1 mutation (PMID:20137773). The cardiovascular phenotype of the disease is quite variable and even between siblings carrying the same mutations. Of two Taiwanese siblings with identical genotype, one developed extensive arterial calcification and severe hypertension, and died of heart failure at the age of 6 weeks, while the other sibling had an uncomplicated clinical course (PMID:28585220).

Symptom Information: Sort by abundance 

1
 (HPO:0002039) Anorexia 21151691 IBIS 62 / 7739
2
 (HPO:0008872) Feeding difficulties in infancy 23430823 IBIS 153 / 7739
3
 (HPO:0002013) Vomiting 23430823; 21151691 IBIS 191 / 7739
4
 (HPO:0000967) Petechiae 21151691 IBIS 26 / 7739
5
 (HPO:0000316) Hypertelorism 22229486 IBIS 644 / 7739
6
 (HPO:0002098) Respiratory distress 22629037; 15940697 IBIS 75 / 7739
7
 (HPO:0001942) Metabolic acidosis 22629037 IBIS 81 / 7739
8
 (HPO:0002148) Hypophosphatemia 29976176 IBIS 43 / 7739
9
 (HPO:0003074) Hyperglycemia 22629037 IBIS 37 / 7739
10
 (MedDRA:10015856) Extrasystoles 21151691 IBIS 1 / 7739
11
 (HPO:0001649) Tachycardia 23430823; 21151691; 22629037 IBIS 53 / 7739
12
 (HPO:0100545) Arterial stenosis 30005391 IBIS 22 / 7739
13
 (HPO:0001635) Congestive heart failure 23430823; 21151691; 22629037; 22229486; 15940697 IBIS 232 / 7739
14
 (HPO:0000822) Hypertension 29976176; 23430823; 22629037 IBIS 224 / 7739
15
 (HPO:0100817) Renovascular hypertension 22229486 IBIS 9 / 7739
16
 (HPO:0001658) Myocardial infarction 30005391; 21151691; 22629037 IBIS 30 / 7739
17
 (HPO:0001279) Syncope 21151691 IBIS 94 / 7739
18
 (HPO:0001903) Anemia 22629037 IBIS 289 / 7739
19
 (HPO:0001263) Global developmental delay 22229486 IBIS 853 / 7739
20
 (HPO:0001288) Gait disturbance 22229486 IBIS 318 / 7739
21
 (HPO:0002069) Generalized tonic-clonic seizures 23430823 IBIS 96 / 7739
22
 (HPO:0001558) Decreased fetal movement 23430823 IBIS 74 / 7739
23
 (HPO:0001561) Polyhydramnios 29976176; 23430823; 22629037 IBIS 191 / 7739
24
 (HPO:0100593) Calcification of cartilage 22229486 IBIS 4 / 7739
25
 (HPO:0001640) Cardiomegaly 23430823; 22629037; 15940697 IBIS 81 / 7739
26
 (HPO:0001712) Left ventricular hypertrophy 23430823 IBIS 76 / 7739
27
 (HPO:0005180) Tricuspid regurgitation 23430823 IBIS 20 / 7739
28
 (HPO:0001638) Cardiomyopathy 22229486 IBIS 192 / 7739
29
 (HPO:0001639) Hypertrophic cardiomyopathy 29976176 IBIS 137 / 7739
30
 (MedDRA:10050510) Ventricular hypokinesia 23430823 IBIS 5 / 7739
31
 (HPO:0001685) Myocardial fibrosis 21151691 IBIS 30 / 7739
32
 (HPO:0004415) Pulmonary artery stenosis 23430823 IBIS 25 / 7739
33
 (HPO:0001999) Abnormal facial shape 22229486 IBIS 169 / 7739
34
 (HPO:0000290) Abnormality of the forehead 22229486 IBIS 5 / 7739
35
 (HPO:0006335) Persistence of primary teeth 29244957 IBIS 12 / 7739
36
 (HPO:0006486) Abnormality of the dental root 29244957 IBIS 1 / 7739
37
 (HPO:0100717) Abnormality of the cementum 29244957 IBIS 2 / 7739
38
 (HPO:0000961) Cyanosis 23430823 IBIS 60 / 7739
39
 (HPO:0008776) Abnormality of the renal artery 29976176; 22629037 IBIS 1 / 7739
40
 (HPO:0001679) Abnormality of the aorta 29976176; 22629037 IBIS 5 / 7739
41
 (HPO:0001717) Coronary artery calcification 30005391; 22629037 IBIS 4 / 7739
42
 (HPO:0005292) Intimal thickening in the coronary arteries 15940697 IBIS 2 / 7739
43
 (HPO:0003207) Arterial calcification 29976176; 23430823; 22629037; 22229486; 15940697 IBIS 2 / 7739
44
 (HPO:0010766) Ectopic calcification 22229486 IBIS 5 / 7739
45
 (HPO:0002789) Tachypnea 23430823; 21151691 IBIS 48 / 7739
46
 (HPO:0000365) Hearing impairment 22229486 IBIS 539 / 7739
47
 (HPO:0001789) Hydrops fetalis 29976176 IBIS 63 / 7739
48
 (HPO:0030149) Cardiogenic shock 30005391 IBIS 4 / 7739
49
 (HPO:0001522) Death in infancy 30005391; 29976176; 23430823; 22629037 IBIS 275 / 7739
50
 (HPO:0040197) Encephalomalacia 23430823 IBIS 1 / 7739
51
 (HPO:0030148) Heart murmur 23430823; 22629037; 15940697 IBIS 29 / 7739
52
 (MedDRA:10037150) Pseudoxanthoma elasticum 22229486 IBIS 1 / 7739

Associated genes:

ENPP1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Generalized arterial calcification of infancy (GACI) is a severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. GACI is often fatal within the first 6 months of ...
Clinical Description OMIM This lesion has been noted in multiple sibs (Hunt and Leys, 1957; Menten and Fetterman, 1948). It may be fundamentally a defect of elastic fiber. Calcification occurs particularly in the internal elastic lamina. Material with the staining properties of ...
Molecular genetics OMIM Spontaneous periarticular and aortic calcifications in early life and systemic lowering of nucleotide pyrophosphatase/phosphodiesterase (NPP) activity and inorganic pyrophosphate levels are shared features of the phenotype of idiopathic infantile arterial calcification (IIAC) and of homozygous 'tiptoe walking' (ttw/ttw) mice, ...