MCID: OST163
MIFTS: 33

Osteopetrosis, Autosomal Recessive 3

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Bone diseases, Fetal diseases, Neuronal diseases, Eye diseases, Blood diseases

Aliases & Classifications for Osteopetrosis, Autosomal Recessive 3

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 3:

Name: Osteopetrosis, Autosomal Recessive 3 57 75 73
Osteopetrosis with Renal Tubular Acidosis 57 12 53 59 75 29 6
Marble Brain Disease 57 12 53 59 75
Guibaud-Vainsel Syndrome 57 12 59 75
Optb3 57 12 53 75
Osteopetrosis, Autosomal Recessive 3, with Renal Tubular Acidosis 57 13
Carbonic Anhydrase Ii Deficiency 57 12
Carbonic Anhydrase 2 Deficiency 53 59
Autosomal Recessive Osteopetrosis 3 with Renal Tubular Acidosis 12
Osteopetrosis, Autosomal Recessive, Type 3 40
Carbonic Anhydrase Ii Deficiency Syndrome 75
Autosomal Recessive Osteopetrosis Type 3 53
Autosomal Recessive Osteopetrosis 3 12
Osteopetrosis Autosomal Recessive 3 53
Renal Tubular Acidosis Type 3 59
Carbonic Anhydrase Ii Variant 6
Mixed Renal Tubular Acidosis 59
Guibaud Vainsel Syndrome 53
Carbonic Anhydrase Ii 13
Mixed Rta 59

Characteristics:

Orphanet epidemiological data:

59
osteopetrosis with renal tubular acidosis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
osteopetrosis, autosomal recessive 3:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Osteopetrosis, Autosomal Recessive 3

NIH Rare Diseases : 53 Osteopetrosis refers to a group of rare, inherited skeletal disorders characterized by increased bone density and abnormal bone growth. Symptoms and severity can vary greatly, ranging from neonatal onset with life-threatening complications (such as bone marrow failure) to the incidental finding of osteopetrosis on X-ray. Depending on severity and age of onset, features may include fractures, short stature, compressive neuropathies (pressure on the nerves), hypocalcemia with attendant tetanic seizures, and life-threatening pancytopenia. In rare cases, there may be neurological impairment or involvement of other body systems. Osteopetrosis may be caused by mutations in at least 10 genes. Inheritance can be autosomal recessive, autosomal dominant, or X-linked recessive with the most severe forms being autosomal recessive. Management depends on the specific symptoms and severity and may include vitamin D supplements, various medications, and/or surgery. Adult osteopetrosis requires no treatment by itself, but complications may require intervention.

MalaCards based summary : Osteopetrosis, Autosomal Recessive 3, also known as osteopetrosis with renal tubular acidosis, is related to osteopetrosis and renal tubular acidosis. An important gene associated with Osteopetrosis, Autosomal Recessive 3 is CA2 (Carbonic Anhydrase 2). Affiliated tissues include bone, brain and bone marrow, and related phenotypes are genu valgum and abnormality of epiphysis morphology

Disease Ontology : 12 An osteopetrosis characterized by autosomal recessive inheritance that has material basis in homozygous or compound heterozygous mutation in the CA2 gene on chromosome 8q21.

UniProtKB/Swiss-Prot : 75 Osteopetrosis, autosomal recessive 3: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.

Description from OMIM: 259730

Related Diseases for Osteopetrosis, Autosomal Recessive 3

Symptoms & Phenotypes for Osteopetrosis, Autosomal Recessive 3

Symptoms via clinical synopsis from OMIM:

57
HEENT:
dental malocclusion
cranial hyperostosis
visual impairment from optic nerve compression

Heme:
anemia
extramedullary hematopoiesis

GI:
hepatosplenomegaly

Neuro:
basal ganglion calcification
normal intelligence or mental retardation

Misc:
onset in first 2 years with fractures

Growth:
short stature

Lab:
periodic hypokalemic paresis
elevated serum acid phosphatase
renal tubular acidosis, type i
osteoclasts fail to form 'ruffled membranes' characteristic of active bone resorbing cells
carbonic anhydrase ii defect

Limbs:
diaphyseal sclerosis

Skel:
osteosclerosis


Clinical features from OMIM:

259730

Human phenotypes related to Osteopetrosis, Autosomal Recessive 3:

59 32 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 genu valgum 59 32 hallmark (90%) Very frequent (99-80%) HP:0002857
2 abnormality of epiphysis morphology 59 32 hallmark (90%) Very frequent (99-80%) HP:0005930
3 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
4 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
5 cerebral calcification 59 32 frequent (33%) Frequent (79-30%) HP:0002514
6 mandibular prognathia 59 32 frequent (33%) Frequent (79-30%) HP:0000303
7 dental malocclusion 59 32 frequent (33%) Frequent (79-30%) HP:0000689
8 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
9 splenomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001744
10 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
11 aseptic necrosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0010885
12 carious teeth 59 32 frequent (33%) Frequent (79-30%) HP:0000670
13 visual impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000505
14 optic atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000648
15 anemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001903
16 peripheral neuropathy 59 32 frequent (33%) Frequent (79-30%) HP:0009830
17 reduced bone mineral density 59 32 hallmark (90%) Very frequent (99-80%) HP:0004349
18 thrombocytopenia 59 32 frequent (33%) Frequent (79-30%) HP:0001873
19 abnormality of the renal tubule 59 32 hallmark (90%) Very frequent (99-80%) HP:0000091
20 recurrent fractures 59 32 hallmark (90%) Very frequent (99-80%) HP:0002757
21 bone pain 59 32 hallmark (90%) Very frequent (99-80%) HP:0002653
22 abnormality of dental morphology 59 32 frequent (33%) Frequent (79-30%) HP:0006482
23 osteopetrosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0011002
24 short stature 32 HP:0004322
25 visual loss 32 HP:0000572
26 periodic hypokalemic paresis 32 HP:0008153
27 cranial hyperostosis 32 HP:0004437
28 hepatosplenomegaly 32 HP:0001433
29 optic nerve compression 32 HP:0007807
30 distal renal tubular acidosis 32 HP:0008341
31 extramedullary hematopoiesis 32 HP:0001978
32 basal ganglia calcification 32 HP:0002135
33 diaphyseal sclerosis 32 HP:0003034
34 elevated serum acid phosphatase 32 HP:0003148

Drugs & Therapeutics for Osteopetrosis, Autosomal Recessive 3

Search Clinical Trials , NIH Clinical Center for Osteopetrosis, Autosomal Recessive 3

Genetic Tests for Osteopetrosis, Autosomal Recessive 3

Genetic tests related to Osteopetrosis, Autosomal Recessive 3:

# Genetic test Affiliating Genes
1 Osteopetrosis with Renal Tubular Acidosis 29 CA2

Anatomical Context for Osteopetrosis, Autosomal Recessive 3

MalaCards organs/tissues related to Osteopetrosis, Autosomal Recessive 3:

41
Bone, Brain, Bone Marrow

Publications for Osteopetrosis, Autosomal Recessive 3

Articles related to Osteopetrosis, Autosomal Recessive 3:

# Title Authors Year
1
Osteopetrosis with renal tubular acidosis and cerebral calcification. ( 29571443 )
2018
2
Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype- phenotype correlation. ( 15300855 )
2004
3
Carbonic anhydrase II deficiency syndrome: recessive osteopetrosis with renal tubular acidosis and cerebral calcification. ( 3081869 )
1986
4
Carbonic anhydrase II deficiency in 12 families with the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. ( 3925334 )
1985
5
Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. ( 6405388 )
1983

Variations for Osteopetrosis, Autosomal Recessive 3

UniProtKB/Swiss-Prot genetic disease variations for Osteopetrosis, Autosomal Recessive 3:

75
# Symbol AA change Variation ID SNP ID
1 CA2 p.Gln92Pro VAR_001381
2 CA2 p.His107Tyr VAR_001382 rs118203933
3 CA2 p.His94Tyr VAR_021009
4 CA2 p.Gly144Arg VAR_021010

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 3:

6
(show all 49)
# Gene Variation Type Significance SNP ID Assembly Location
1 CA2 NM_000067.2(CA2): c.52A> G (p.Lys18Glu) single nucleotide variant Pathogenic rs118203931 GRCh37 Chromosome 8, 86377518: 86377518
2 CA2 NM_000067.2(CA2): c.52A> G (p.Lys18Glu) single nucleotide variant Pathogenic rs118203931 GRCh38 Chromosome 8, 85465289: 85465289
3 CA2 NM_000067.2(CA2): c.707C> A (p.Pro236His) single nucleotide variant Pathogenic rs118203932 GRCh37 Chromosome 8, 86392942: 86392942
4 CA2 NM_000067.2(CA2): c.707C> A (p.Pro236His) single nucleotide variant Pathogenic rs118203932 GRCh38 Chromosome 8, 85480713: 85480713
5 CA2 NM_000067.2(CA2): c.319C> T (p.His107Tyr) single nucleotide variant Pathogenic rs118203933 GRCh37 Chromosome 8, 86386008: 86386008
6 CA2 NM_000067.2(CA2): c.319C> T (p.His107Tyr) single nucleotide variant Pathogenic rs118203933 GRCh38 Chromosome 8, 85473779: 85473779
7 CA2 CA2, IVS5AS, G-C, -1 single nucleotide variant Pathogenic
8 CA2 CA2, IVS2DS, G-A, +1 single nucleotide variant Pathogenic
9 CA2 NM_000067.2(CA2): c.120T> G (p.Tyr40Ter) single nucleotide variant Pathogenic rs118203934 GRCh37 Chromosome 8, 86377586: 86377586
10 CA2 NM_000067.2(CA2): c.120T> G (p.Tyr40Ter) single nucleotide variant Pathogenic rs118203934 GRCh38 Chromosome 8, 85465357: 85465357
11 CA2 CA2, 1-BP DEL, 207C deletion Pathogenic
12 CA2 NM_000067.2(CA2): c.562T> C (p.Leu188=) single nucleotide variant Benign rs703 GRCh37 Chromosome 8, 86389403: 86389403
13 CA2 NM_000067.2(CA2): c.562T> C (p.Leu188=) single nucleotide variant Benign rs703 GRCh38 Chromosome 8, 85477174: 85477174
14 CA2 NM_000067.2(CA2): c.232+1G> A single nucleotide variant Pathogenic rs573750741 GRCh37 Chromosome 8, 86377699: 86377699
15 CA2 NM_000067.2(CA2): c.232+1G> A single nucleotide variant Pathogenic rs573750741 GRCh38 Chromosome 8, 85465470: 85465470
16 CA2 NM_000067.2(CA2): c.-130C> A single nucleotide variant Uncertain significance rs570970117 GRCh37 Chromosome 8, 86376181: 86376181
17 CA2 NM_000067.2(CA2): c.-130C> A single nucleotide variant Uncertain significance rs570970117 GRCh38 Chromosome 8, 85463952: 85463952
18 CA2 NM_000067.2(CA2): c.-84_-82dupCCC duplication Uncertain significance rs886063147 GRCh37 Chromosome 8, 86376227: 86376229
19 CA2 NM_000067.2(CA2): c.-84_-82dupCCC duplication Uncertain significance rs886063147 GRCh38 Chromosome 8, 85463998: 85464000
20 CA2 NM_000067.2(CA2): c.508-7G> A single nucleotide variant Uncertain significance rs886063149 GRCh37 Chromosome 8, 86389342: 86389342
21 CA2 NM_000067.2(CA2): c.508-7G> A single nucleotide variant Uncertain significance rs886063149 GRCh38 Chromosome 8, 85477113: 85477113
22 CA2 NM_000067.2(CA2): c.*374A> G single nucleotide variant Uncertain significance rs886063151 GRCh37 Chromosome 8, 86393392: 86393392
23 CA2 NM_000067.2(CA2): c.*374A> G single nucleotide variant Uncertain significance rs886063151 GRCh38 Chromosome 8, 85481163: 85481163
24 CA2 NM_000067.2(CA2): c.*465A> C single nucleotide variant Uncertain significance rs886063152 GRCh37 Chromosome 8, 86393483: 86393483
25 CA2 NM_000067.2(CA2): c.*465A> C single nucleotide variant Uncertain significance rs886063152 GRCh38 Chromosome 8, 85481254: 85481254
26 CA2 NM_000067.2(CA2): c.-176C> T single nucleotide variant Uncertain significance rs886063146 GRCh37 Chromosome 8, 86376135: 86376135
27 CA2 NM_000067.2(CA2): c.-176C> T single nucleotide variant Uncertain significance rs886063146 GRCh38 Chromosome 8, 85463906: 85463906
28 CA2 NM_000067.2(CA2): c.-138G> A single nucleotide variant Uncertain significance rs557422827 GRCh38 Chromosome 8, 85463944: 85463944
29 CA2 NM_000067.2(CA2): c.-138G> A single nucleotide variant Uncertain significance rs557422827 GRCh37 Chromosome 8, 86376173: 86376173
30 CA2 NM_000067.2(CA2): c.*17G> A single nucleotide variant Uncertain significance rs140653628 GRCh37 Chromosome 8, 86393035: 86393035
31 CA2 NM_000067.2(CA2): c.*17G> A single nucleotide variant Uncertain significance rs140653628 GRCh38 Chromosome 8, 85480806: 85480806
32 CA2 NM_000067.2(CA2): c.-53G> T single nucleotide variant Uncertain significance rs886063148 GRCh37 Chromosome 8, 86376258: 86376258
33 CA2 NM_000067.2(CA2): c.-53G> T single nucleotide variant Uncertain significance rs886063148 GRCh38 Chromosome 8, 85464029: 85464029
34 CA2 NM_000067.2(CA2): c.539C> T (p.Pro180Leu) single nucleotide variant Uncertain significance rs886063150 GRCh37 Chromosome 8, 86389380: 86389380
35 CA2 NM_000067.2(CA2): c.539C> T (p.Pro180Leu) single nucleotide variant Uncertain significance rs886063150 GRCh38 Chromosome 8, 85477151: 85477151
36 CA2 NM_000067.2(CA2): c.40G> A (p.Glu14Lys) single nucleotide variant Uncertain significance rs758659684 GRCh37 Chromosome 8, 86377506: 86377506
37 CA2 NM_000067.2(CA2): c.40G> A (p.Glu14Lys) single nucleotide variant Uncertain significance rs758659684 GRCh38 Chromosome 8, 85465277: 85465277
38 CA2 NM_000067.2(CA2): c.648C> T (p.Ser216=) single nucleotide variant Uncertain significance rs376387073 GRCh37 Chromosome 8, 86389489: 86389489
39 CA2 NM_000067.2(CA2): c.648C> T (p.Ser216=) single nucleotide variant Uncertain significance rs376387073 GRCh38 Chromosome 8, 85477260: 85477260
40 CA2 NM_000067.2(CA2): c.*212A> G single nucleotide variant Likely benign rs73263450 GRCh37 Chromosome 8, 86393230: 86393230
41 CA2 NM_000067.2(CA2): c.*212A> G single nucleotide variant Likely benign rs73263450 GRCh38 Chromosome 8, 85481001: 85481001
42 CA2 NM_000067.2(CA2): c.*303C> T single nucleotide variant Uncertain significance rs150089617 GRCh38 Chromosome 8, 85481092: 85481092
43 CA2 NM_000067.2(CA2): c.*303C> T single nucleotide variant Uncertain significance rs150089617 GRCh37 Chromosome 8, 86393321: 86393321
44 CA2 NM_000067.2(CA2): c.*562T> C single nucleotide variant Uncertain significance rs886063153 GRCh37 Chromosome 8, 86393580: 86393580
45 CA2 NM_000067.2(CA2): c.*562T> C single nucleotide variant Uncertain significance rs886063153 GRCh38 Chromosome 8, 85481351: 85481351
46 CA2 NM_000067.2(CA2): c.-181A> T single nucleotide variant Benign rs11261477 GRCh38 Chromosome 8, 85463901: 85463901
47 CA2 NM_000067.2(CA2): c.-181A> T single nucleotide variant Benign rs11261477 GRCh37 Chromosome 8, 86376130: 86376130
48 CA2 NM_000067.2(CA2): c.21C> A (p.Tyr7Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 8, 86376331: 86376331
49 CA2 NM_000067.2(CA2): c.21C> A (p.Tyr7Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 8, 85464102: 85464102

Expression for Osteopetrosis, Autosomal Recessive 3

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Pathways for Osteopetrosis, Autosomal Recessive 3

GO Terms for Osteopetrosis, Autosomal Recessive 3

Sources for Osteopetrosis, Autosomal Recessive 3

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