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Combined oxidative phosphorylation deficiency 53(COXPD53)

MedGen UID:
1779083
Concept ID:
C5543631
Disease or Syndrome
Synonyms: COXPD53; ELBRACHT-ISIKAY SYNDROME; GLOBAL DEVELOPMENTAL DELAY, PROGRESSIVE MICROCEPHALY, STRUCTURAL BRAIN ABNORMALITIES, AND AUTOINFLAMMATION
 
Gene (location): C2orf69 (2q33.1)
 
Monarch Initiative: MONDO:0030378
OMIM®: 619423

Definition

Combined oxidative phosphorylation deficiency-53 (COXPD53) is an autosomal recessive disorder characterized by hypomyelination, microcephaly, liver dysfunction, and recurrent autoinflammation (summary by Lausberg et al., 2021). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). [from OMIM]

Clinical features

From HPO
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Dysplastic corpus callosum
MedGen UID:
98128
Concept ID:
C0431369
Congenital Abnormality
Dysplasia and dysgenesis of the corpus callosum are nonspecific descriptions that imply defective development of the corpus callosum. The term dysplasia is applied when the morphology of the corpus callosum is altered as a congenital trait. For instance, the corpus callosum may be hump-shaped, kinked, or a striped corpus callosum that lacks an anatomically distinct genu and splenium.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
CNS hypomyelination
MedGen UID:
892446
Concept ID:
C4025616
Finding
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
Hypochromic microcytic anemia
MedGen UID:
124413
Concept ID:
C0271901
Disease or Syndrome
A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes.
Arthritis
MedGen UID:
2043
Concept ID:
C0003864
Disease or Syndrome
Inflammation of a joint.
Infective arthritis
MedGen UID:
13918
Concept ID:
C0003869
Disease or Syndrome
The inflammation of one or more joints caused by any infectious pathogen within the joint space. Symptoms include pain, stiffness, and decreased range of motion in the affected joint.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Secondary microcephaly
MedGen UID:
608952
Concept ID:
C0431352
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.

Professional guidelines

PubMed

Alikhani M, Saberi S, Esmaeili M, Michel V, Tashakoripour M, Abdirad A, Aghakhani A, Eybpoosh S, Vosough M, Mohagheghi MA, Eshagh Hosseini M, Touati E, Mohammadi M
Iran Biomed J 2021 Sep 1;25(5):323-33. Epub 2021 Aug 22 doi: 10.52547/ibj.25.5.323. PMID: 34425651Free PMC Article
He M, Cornelis MC, Franks PW, Zhang C, Hu FB, Qi L
Arterioscler Thromb Vasc Biol 2010 Feb;30(2):327-32. Epub 2009 Nov 12 doi: 10.1161/ATVBAHA.109.196196. PMID: 19910641Free PMC Article
Maagaard A, Holberg-Petersen M, Kvittingen EA, Sandvik L, Bruun JN
HIV Med 2006 Jan;7(1):53-8. doi: 10.1111/j.1468-1293.2005.00336.x. PMID: 16313293

Recent clinical studies

Etiology

Paul KC, Krolewski RC, Lucumi Moreno E, Blank J, Holton KM, Ahfeldt T, Furlong M, Yu Y, Cockburn M, Thompson LK, Kreymerman A, Ricci-Blair EM, Li YJ, Patel HB, Lee RT, Bronstein J, Rubin LL, Khurana V, Ritz B
Nat Commun 2023 May 16;14(1):2803. doi: 10.1038/s41467-023-38215-z. PMID: 37193692Free PMC Article
Rafehi H, Read J, Szmulewicz DJ, Davies KC, Snell P, Fearnley LG, Scott L, Thomsen M, Gillies G, Pope K, Bennett MF, Munro JE, Ngo KJ, Chen L, Wallis MJ, Butler EG, Kumar KR, Wu KH, Tomlinson SE, Tisch S, Malhotra A, Lee-Archer M, Dolzhenko E, Eberle MA, Roberts LJ, Fogel BL, Brüggemann N, Lohmann K, Delatycki MB, Bahlo M, Lockhart PJ
Am J Hum Genet 2023 Jan 5;110(1):105-119. Epub 2022 Dec 8 doi: 10.1016/j.ajhg.2022.11.015. PMID: 36493768Free PMC Article
Zhao B, Dai T, Zhao D, Ma X, Zhao C, Li L, Sun Y, Zhang Y, Yan Y, Lu JQ, Liu F, Yan C
Neurol Neuroimmunol Neuroinflamm 2022 Jul;9(4) Epub 2022 May 17 doi: 10.1212/NXI.0000000000001184. PMID: 35581006Free PMC Article
Moody S, Senkin S, Islam SMA, Wang J, Nasrollahzadeh D, Cortez Cardoso Penha R, Fitzgerald S, Bergstrom EN, Atkins J, He Y, Khandekar A, Smith-Byrne K, Carreira C, Gaborieau V, Latimer C, Thomas E, Abnizova I, Bucciarelli PE, Jones D, Teague JW, Abedi-Ardekani B, Serra S, Scoazec JY, Saffar H, Azmoudeh-Ardalan F, Sotoudeh M, Nikmanesh A, Poustchi H, Niavarani A, Gharavi S, Eden M, Richman P, Campos LS, Fitzgerald RC, Ribeiro LF, Soares-Lima SC, Dzamalala C, Mmbaga BT, Shibata T, Menya D, Goldstein AM, Hu N, Malekzadeh R, Fazel A, McCormack V, McKay J, Perdomo S, Scelo G, Chanudet E, Humphreys L, Alexandrov LB, Brennan P, Stratton MR
Nat Genet 2021 Nov;53(11):1553-1563. Epub 2021 Oct 18 doi: 10.1038/s41588-021-00928-6. PMID: 34663923
Voet NB, van der Kooi EL, van Engelen BG, Geurts AC
Cochrane Database Syst Rev 2019 Dec 6;12(12):CD003907. doi: 10.1002/14651858.CD003907.pub5. PMID: 31808555Free PMC Article

Diagnosis

Rafehi H, Read J, Szmulewicz DJ, Davies KC, Snell P, Fearnley LG, Scott L, Thomsen M, Gillies G, Pope K, Bennett MF, Munro JE, Ngo KJ, Chen L, Wallis MJ, Butler EG, Kumar KR, Wu KH, Tomlinson SE, Tisch S, Malhotra A, Lee-Archer M, Dolzhenko E, Eberle MA, Roberts LJ, Fogel BL, Brüggemann N, Lohmann K, Delatycki MB, Bahlo M, Lockhart PJ
Am J Hum Genet 2023 Jan 5;110(1):105-119. Epub 2022 Dec 8 doi: 10.1016/j.ajhg.2022.11.015. PMID: 36493768Free PMC Article
Zhao B, Dai T, Zhao D, Ma X, Zhao C, Li L, Sun Y, Zhang Y, Yan Y, Lu JQ, Liu F, Yan C
Neurol Neuroimmunol Neuroinflamm 2022 Jul;9(4) Epub 2022 May 17 doi: 10.1212/NXI.0000000000001184. PMID: 35581006Free PMC Article
Herman I, Lopez MA, Marafi D, Pehlivan D, Calame DG, Abid F, Lotze TE
Muscle Nerve 2021 Mar;63(3):304-310. Epub 2020 Nov 13 doi: 10.1002/mus.27112. PMID: 33146414
Voet NB, van der Kooi EL, van Engelen BG, Geurts AC
Cochrane Database Syst Rev 2019 Dec 6;12(12):CD003907. doi: 10.1002/14651858.CD003907.pub5. PMID: 31808555Free PMC Article
Sommerville EW, Ng YS, Alston CL, Dallabona C, Gilberti M, He L, Knowles C, Chin SL, Schaefer AM, Falkous G, Murdoch D, Longman C, de Visser M, Bindoff LA, Rawles JM, Dean JCS, Petty RK, Farrugia ME, Haack TB, Prokisch H, McFarland R, Turnbull DM, Donnini C, Taylor RW, Gorman GS
JAMA Neurol 2017 Jun 1;74(6):686-694. doi: 10.1001/jamaneurol.2016.4357. PMID: 28395030Free PMC Article

Therapy

Zhao B, Dai T, Zhao D, Ma X, Zhao C, Li L, Sun Y, Zhang Y, Yan Y, Lu JQ, Liu F, Yan C
Neurol Neuroimmunol Neuroinflamm 2022 Jul;9(4) Epub 2022 May 17 doi: 10.1212/NXI.0000000000001184. PMID: 35581006Free PMC Article
Madeddu G, Fiore V, Melis M, Ortu S, Mannu F, Muredda AA, Garrucciu G, Bandiera F, Zaru S, Bagella P, Calvisi DF, Babudieri S
Sci Rep 2020 Feb 6;10(1):2014. doi: 10.1038/s41598-020-58837-3. PMID: 32029790Free PMC Article
Voet NB, van der Kooi EL, van Engelen BG, Geurts AC
Cochrane Database Syst Rev 2019 Dec 6;12(12):CD003907. doi: 10.1002/14651858.CD003907.pub5. PMID: 31808555Free PMC Article
Greising SM, Corona BT, McGann C, Frankum JK, Warren GL
Tissue Eng Part B Rev 2019 Dec;25(6):510-525. Epub 2019 Nov 11 doi: 10.1089/ten.TEB.2019.0207. PMID: 31578930
Saccà F, Puorro G, Antenora A, Marsili A, Denaro A, Piro R, Sorrentino P, Pane C, Tessa A, Brescia Morra V, Cocozza S, De Michele G, Santorelli FM, Filla A
PLoS One 2011 Mar 11;6(3):e17627. doi: 10.1371/journal.pone.0017627. PMID: 21412413Free PMC Article

Prognosis

Tang C, Shi F, Ji Y, Zhu J, Gu X
Heart Lung Circ 2024 Feb;33(2):230-239. Epub 2024 Jan 4 doi: 10.1016/j.hlc.2023.11.012. PMID: 38177014
Moody S, Senkin S, Islam SMA, Wang J, Nasrollahzadeh D, Cortez Cardoso Penha R, Fitzgerald S, Bergstrom EN, Atkins J, He Y, Khandekar A, Smith-Byrne K, Carreira C, Gaborieau V, Latimer C, Thomas E, Abnizova I, Bucciarelli PE, Jones D, Teague JW, Abedi-Ardekani B, Serra S, Scoazec JY, Saffar H, Azmoudeh-Ardalan F, Sotoudeh M, Nikmanesh A, Poustchi H, Niavarani A, Gharavi S, Eden M, Richman P, Campos LS, Fitzgerald RC, Ribeiro LF, Soares-Lima SC, Dzamalala C, Mmbaga BT, Shibata T, Menya D, Goldstein AM, Hu N, Malekzadeh R, Fazel A, McCormack V, McKay J, Perdomo S, Scelo G, Chanudet E, Humphreys L, Alexandrov LB, Brennan P, Stratton MR
Nat Genet 2021 Nov;53(11):1553-1563. Epub 2021 Oct 18 doi: 10.1038/s41588-021-00928-6. PMID: 34663923
Sundquist K, Ahmad A, Svensson PJ, Zöller B, Sundquist J, Memon AA
J Thromb Thrombolysis 2018 Aug;46(2):154-165. doi: 10.1007/s11239-018-1662-x. PMID: 29671165
Wang YJ, Khan FI, Xu Q, Wei DQ
Curr Protein Pept Sci 2018;19(5):507-522. doi: 10.2174/1389203718666161108095052. PMID: 27829346
Sommerville EW, Ng YS, Alston CL, Dallabona C, Gilberti M, He L, Knowles C, Chin SL, Schaefer AM, Falkous G, Murdoch D, Longman C, de Visser M, Bindoff LA, Rawles JM, Dean JCS, Petty RK, Farrugia ME, Haack TB, Prokisch H, McFarland R, Turnbull DM, Donnini C, Taylor RW, Gorman GS
JAMA Neurol 2017 Jun 1;74(6):686-694. doi: 10.1001/jamaneurol.2016.4357. PMID: 28395030Free PMC Article

Clinical prediction guides

Tang C, Shi F, Ji Y, Zhu J, Gu X
Heart Lung Circ 2024 Feb;33(2):230-239. Epub 2024 Jan 4 doi: 10.1016/j.hlc.2023.11.012. PMID: 38177014
Rafehi H, Read J, Szmulewicz DJ, Davies KC, Snell P, Fearnley LG, Scott L, Thomsen M, Gillies G, Pope K, Bennett MF, Munro JE, Ngo KJ, Chen L, Wallis MJ, Butler EG, Kumar KR, Wu KH, Tomlinson SE, Tisch S, Malhotra A, Lee-Archer M, Dolzhenko E, Eberle MA, Roberts LJ, Fogel BL, Brüggemann N, Lohmann K, Delatycki MB, Bahlo M, Lockhart PJ
Am J Hum Genet 2023 Jan 5;110(1):105-119. Epub 2022 Dec 8 doi: 10.1016/j.ajhg.2022.11.015. PMID: 36493768Free PMC Article
Wang YJ, Khan FI, Xu Q, Wei DQ
Curr Protein Pept Sci 2018;19(5):507-522. doi: 10.2174/1389203718666161108095052. PMID: 27829346
Blacker TS, Duchen MR
Free Radic Biol Med 2016 Nov;100:53-65. Epub 2016 Aug 9 doi: 10.1016/j.freeradbiomed.2016.08.010. PMID: 27519271Free PMC Article
Spiegel R, Saada A, Flannery PJ, Burté F, Soiferman D, Khayat M, Eisner V, Vladovski E, Taylor RW, Bindoff LA, Shaag A, Mandel H, Schuler-Furman O, Shalev SA, Elpeleg O, Yu-Wai-Man P
J Med Genet 2016 Feb;53(2):127-31. Epub 2015 Nov 11 doi: 10.1136/jmedgenet-2015-103361. PMID: 26561570Free PMC Article

Recent systematic reviews

Voet NB, van der Kooi EL, van Engelen BG, Geurts AC
Cochrane Database Syst Rev 2019 Dec 6;12(12):CD003907. doi: 10.1002/14651858.CD003907.pub5. PMID: 31808555Free PMC Article
Greising SM, Corona BT, McGann C, Frankum JK, Warren GL
Tissue Eng Part B Rev 2019 Dec;25(6):510-525. Epub 2019 Nov 11 doi: 10.1089/ten.TEB.2019.0207. PMID: 31578930

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