Hypophosphatemic rickets, autosomal recessive, 2

General Information (adopted from Orphanet):

Synonyms, Signs: ARHR2
Number of Symptoms 21
OrphanetNr:
OMIM Id: 613312
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
24216977 [IBIS]
Age of onset: Neonatal
24216977 [IBIS]

Disease classification (adopted from Orphanet):

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

Comment:

Ecto/nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) loss-of-function mutations cause generalized arterial calcification of infancy evolving towards hypophosphatemic rickets (PMID:24216977). 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).

Symptom Information: Sort by abundance 

1
(HPO:0003155) Elevated alkaline phosphatase 20137772; 20137773 IBIS 52 / 7739
2
(HPO:0004322) Short stature 20137772; 20137773 IBIS 1232 / 7739
3
(HPO:0002148) Hypophosphatemia 24216977; 20137772; 20137773 IBIS 43 / 7739
4
(HPO:0004912) Hypophosphatemic rickets 24216977; 20137772; 20137773 IBIS 13 / 7739
5
(HPO:0001635) Congestive heart failure 24216977 IBIS 232 / 7739
6
(HPO:0100817) Renovascular hypertension 24216977 IBIS 9 / 7739
7
(HPO:0002673) Coxa valga 20137773 IBIS 57 / 7739
8
(HPO:0002857) Genu valgum 20137772; 20137773 IBIS 144 / 7739
9
(HPO:0002970) Genu varum 20137773 IBIS 60 / 7739
10
(HPO:0002979) Bowing of the legs 20137772 IBIS 28 / 7739
11
(HPO:0003019) Abnormality of the wrist 20137772 IBIS 52 / 7739
12
(HPO:0002748) Rickets 24216977; 20137772; 20137773 IBIS 41 / 7739
13
(HPO:0002750) Delayed skeletal maturation 20137772 IBIS 250 / 7739
14
(HPO:0001639) Hypertrophic cardiomyopathy 24216977 IBIS 137 / 7739
15
(HPO:0000685) Hypoplasia of teeth 20137772 IBIS 12 / 7739
16
(HPO:0030757) Tooth abscess 24216977 IBIS 1 / 7739
17
(HPO:0000670) Carious teeth 20137772 IBIS 145 / 7739
18
(HPO:0000121) Nephrocalcinosis 20137773 IBIS 57 / 7739
19
(HPO:0004940) Generalized arterial calcification 24216977 IBIS 2 / 7739
20
(HPO:0003109) Hyperphosphaturia 24216977; 20137772; 20137773 IBIS 18 / 7739
21
(HPO:0000365) Hearing impairment 24216977 IBIS 539 / 7739

Associated genes:

ENPP1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Molecular genetics OMIM In a cohort of 60 probands with autosomal recessive hypophosphatemic rickets, who were negative for mutation in known hypophosphatemia genes, Lorenz-Depiereux et al. (2010) sequenced the candidate gene ENPP1 (173335) and identified homozygosity for a deletion, missense, or frameshift ...