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Osteopetrosis, autosomal dominant 3(OPTA3)

MedGen UID:
1648454
Concept ID:
C4748197
Disease or Syndrome
Synonyms: OPTA3; OSTEOPETROSIS, AUTOSOMAL DOMINANT 3
 
Gene (location): PLEKHM1 (17q21.31)
 
Monarch Initiative: MONDO:0020848
OMIM®: 618107

Definition

Autosomal dominant osteopetrosis-3 (OPTA3) is characterized by phenotypic variability. Some patients have typical features of osteopetrosis, including fractures after minor trauma, early tooth loss, anemia, hepatosplenomegaly, and a generalized increase in bone mineral density, whereas other patients exhibit localized osteosclerosis and generalized osteopenia. OPTA3 represents a relatively malignant form of osteopetrosis in some patients who develop significant pancytopenia and hepatosplenomegaly (Bo et al., 2016). For a discussion of genetic heterogeneity of autosomal dominant osteopetrosis, see OPTA1 (607634). [from OMIM]

Clinical features

From HPO
Asthenia
MedGen UID:
2107
Concept ID:
C0004093
Sign or Symptom
A state characterized by a feeling of weakness and loss of strength leading to a generalized weakness of the body.
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Recurrent fractures
MedGen UID:
42094
Concept ID:
C0016655
Injury or Poisoning
The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture).
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Gingivitis
MedGen UID:
4895
Concept ID:
C0017574
Disease or Syndrome
Inflammation of the gingiva.
Premature loss of teeth
MedGen UID:
66678
Concept ID:
C0232513
Finding
Exfoliation of a tooth more than 2 SD earlier than the normal age for the deciduous teeth and not related to traume or neglect. Exfoliation of a permanent tooth is per se abnormal.
Hyperparathyroidism
MedGen UID:
6967
Concept ID:
C0020502
Disease or Syndrome
Excessive production of parathyroid hormone (PTH) by the parathyroid glands.

Recent clinical studies

Etiology

Wang Z, Li X, Wang Y, Fu W, Liu Y, Zhang Z, Wang C
Front Endocrinol (Lausanne) 2022;13:819641. Epub 2022 Mar 17 doi: 10.3389/fendo.2022.819641. PMID: 35370969Free PMC Article
Butscheidt S, Rolvien T, Kornak U, Schmidt FN, Schinke T, Amling M, Oheim R
Calcif Tissue Int 2018 Jan;102(1):41-52. Epub 2017 Oct 10 doi: 10.1007/s00223-017-0332-x. PMID: 29018903
Aggarwal S
Gene 2013 Oct 1;528(1):41-5. Epub 2013 May 5 doi: 10.1016/j.gene.2013.04.069. PMID: 23657117
Waguespack SG, Hui SL, Dimeglio LA, Econs MJ
J Clin Endocrinol Metab 2007 Mar;92(3):771-8. Epub 2006 Dec 12 doi: 10.1210/jc.2006-1986. PMID: 17164308
Waguespack SG, Koller DL, White KE, Fishburn T, Carn G, Buckwalter KA, Johnson M, Kocisko M, Evans WE, Foroud T, Econs MJ
J Bone Miner Res 2003 Aug;18(8):1513-8. doi: 10.1359/jbmr.2003.18.8.1513. PMID: 12929941

Diagnosis

Wang Z, Li X, Wang Y, Fu W, Liu Y, Zhang Z, Wang C
Front Endocrinol (Lausanne) 2022;13:819641. Epub 2022 Mar 17 doi: 10.3389/fendo.2022.819641. PMID: 35370969Free PMC Article
Butscheidt S, Rolvien T, Kornak U, Schmidt FN, Schinke T, Amling M, Oheim R
Calcif Tissue Int 2018 Jan;102(1):41-52. Epub 2017 Oct 10 doi: 10.1007/s00223-017-0332-x. PMID: 29018903
Aggarwal S
Gene 2013 Oct 1;528(1):41-5. Epub 2013 May 5 doi: 10.1016/j.gene.2013.04.069. PMID: 23657117
Batlle D, Haque SK
Nephrol Dial Transplant 2012 Oct;27(10):3691-704. doi: 10.1093/ndt/gfs442. PMID: 23114896
Rodríguez-Soriano J
Pediatr Nephrol 2000 Oct;14(12):1121-36. doi: 10.1007/s004670000407. PMID: 11045400

Therapy

Imel EA, Liu Z, Acton D, Coffman M, Gebregziabher N, Tong Y, Econs MJ
J Bone Miner Res 2019 Aug;34(8):1436-1445. Epub 2019 May 13 doi: 10.1002/jbmr.3715. PMID: 30889272Free PMC Article
Zhang ZF, Wang D, Wu LD, Dai XS
Chin J Traumatol 2017 Jun;20(3):173-176. Epub 2017 May 10 doi: 10.1016/j.cjtee.2017.02.001. PMID: 28550971Free PMC Article
Arruda M, Coelho MC, Moraes AB, de Paula Paranhos-Neto F, Madeira M, Farias ML, Vieira Neto L
J Bone Miner Res 2016 Mar;31(3):657-62. Epub 2015 Oct 20 doi: 10.1002/jbmr.2715. PMID: 26387875

Prognosis

Jodeh W, Katz AJ, Hart M, Warden SJ, Niziolek P, Alam I, Ing S, Polgreen LE, Imel EA, Econs MJ
J Clin Endocrinol Metab 2024 Jun 17;109(7):1726-1732. doi: 10.1210/clinem/dgae040. PMID: 38261998Free PMC Article
Dulski J, Souza J, Santos ML, Wszolek ZK
Orphanet J Rare Dis 2023 Jun 22;18(1):160. doi: 10.1186/s13023-023-02772-9. PMID: 37349768Free PMC Article
Wang Z, Li X, Wang Y, Fu W, Liu Y, Zhang Z, Wang C
Front Endocrinol (Lausanne) 2022;13:819641. Epub 2022 Mar 17 doi: 10.3389/fendo.2022.819641. PMID: 35370969Free PMC Article
Dharamshi HA, Ahmed SA, Mohsin AA, Mustahsan SM, Devi R, Iqbal A, Abidi SM
J Ayub Med Coll Abbottabad 2016 Jan-Mar;28(1):191-3. PMID: 27323593
Zheng H, Shao C, Zheng Y, He JW, Fu WZ, Wang C, Zhang ZL
J Bone Miner Metab 2016 Jul;34(4):440-6. Epub 2015 Jun 9 doi: 10.1007/s00774-015-0682-2. PMID: 26056022

Clinical prediction guides

Jodeh W, Katz AJ, Hart M, Warden SJ, Niziolek P, Alam I, Ing S, Polgreen LE, Imel EA, Econs MJ
J Clin Endocrinol Metab 2024 Jun 17;109(7):1726-1732. doi: 10.1210/clinem/dgae040. PMID: 38261998Free PMC Article
Dulski J, Souza J, Santos ML, Wszolek ZK
Orphanet J Rare Dis 2023 Jun 22;18(1):160. doi: 10.1186/s13023-023-02772-9. PMID: 37349768Free PMC Article
Ladd LM, Imel EA, Niziolek PJ, Liu Z, Warden SJ, Liang Y, Econs MJ
Skeletal Radiol 2021 May;50(5):903-913. Epub 2020 Oct 3 doi: 10.1007/s00256-020-03625-3. PMID: 33009917Free PMC Article
Butscheidt S, Rolvien T, Kornak U, Schmidt FN, Schinke T, Amling M, Oheim R
Calcif Tissue Int 2018 Jan;102(1):41-52. Epub 2017 Oct 10 doi: 10.1007/s00223-017-0332-x. PMID: 29018903
Alam I, McQueen AK, Acton D, Reilly AM, Gerard-O'Riley RL, Oakes DK, Kasipathi C, Huffer A, Wright WB, Econs MJ
Bone 2017 Jan;94:34-41. Epub 2016 Oct 14 doi: 10.1016/j.bone.2016.10.016. PMID: 27746321

Recent systematic reviews

Dulski J, Souza J, Santos ML, Wszolek ZK
Orphanet J Rare Dis 2023 Jun 22;18(1):160. doi: 10.1186/s13023-023-02772-9. PMID: 37349768Free PMC Article

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