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Combined oxidative phosphorylation defect type 13(COXPD13)

MedGen UID:
1631854
Concept ID:
C4706283
Disease or Syndrome
Synonym: Combined oxidative phosphorylation deficiency 13
SNOMED CT: Combined oxidative phosphorylation defect type 13 (763110007); COXPD13 - combined oxidative phosphorylation defect type 13 (763110007)
 
Gene (location): PNPT1 (2p16.1)
 
Monarch Initiative: MONDO:0013977
OMIM®: 614932
Orphanet: ORPHA319514

Definition

Combined oxidative phosphorylation deficiency-13 (COXPD13) is an autosomal recessive multisystem disorder resulting from mitochondrial dysfunction. Affected individuals develop severe neurologic impairment in the first months of life, including hypotonia, abnormal dystonic movements, hearing loss, poor feeding, global developmental delay, and abnormal eye movements. Brain imaging shows signal abnormalities in putamen, basal ganglia, caudate nuclei, or corpus callosum, as well as delayed myelination. Analysis of patient tissues shows multiple defects in enzymatic activities of the mitochondrial respiratory chain, although some tissues may show normal values since tissue expression of the mitochondrial defect and metabolic needs of specific tissues are variable (summary by Vedrenne et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). [from OMIM]

Clinical features

From HPO
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Decreased mitochondrial complex III activity in liver tissue
MedGen UID:
870574
Concept ID:
C4025022
Finding
Decreased activity of complex III of the mitochondrion in the liver.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Leukodystrophy
MedGen UID:
6070
Concept ID:
C0023520
Disease or Syndrome
Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Increased CSF lactate
MedGen UID:
257904
Concept ID:
C1167918
Finding
Increased concentration of lactate in the cerebrospinal fluid.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Decreased nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Poor head control
MedGen UID:
322809
Concept ID:
C1836038
Finding
Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months.
Severe muscular hypotonia
MedGen UID:
326544
Concept ID:
C1839630
Finding
A severe degree of muscular hypotonia characterized by markedly reduced muscle tone.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Abnormality of eye movement
MedGen UID:
99227
Concept ID:
C0497202
Finding
An abnormality in voluntary or involuntary eye movements or their control.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

Ni M, Black LF, Pan C, Vu H, Pei J, Ko B, Cai L, Solmonson A, Yang C, Nugent KM, Grishin NV, Xing C, Roeder E, DeBerardinis RJ
J Inherit Metab Dis 2021 Jul;44(4):949-960. Epub 2021 Apr 27 doi: 10.1002/jimd.12387. PMID: 33855712Free PMC Article
Cízková A, Stránecký V, Ivánek R, Hartmannová H, Nosková L, Piherová L, Tesarová M, Hansíková H, Honzík T, Zeman J, Divina P, Potocká A, Paul J, Sperl W, Mayr JA, Seneca S, Houstĕk J, Kmoch S
BMC Genomics 2008 Jan 25;9:38. doi: 10.1186/1471-2164-9-38. PMID: 18221507Free PMC Article

Diagnosis

Lei YQ, Ye ZJ, Wei YL, Zhu LP, Zhuang XD, Wang XR, Cao H
Sci Rep 2023 May 2;13(1):7134. doi: 10.1038/s41598-023-32572-x. PMID: 37130848Free PMC Article
Gardeitchik T, Mohamed M, Ruzzenente B, Karall D, Guerrero-Castillo S, Dalloyaux D, van den Brand M, van Kraaij S, van Asbeck E, Assouline Z, Rio M, de Lonlay P, Scholl-Buergi S, Wolthuis DFGJ, Hoischen A, Rodenburg RJ, Sperl W, Urban Z, Brandt U, Mayr JA, Wong S, de Brouwer APM, Nijtmans L, Munnich A, Rötig A, Wevers RA, Metodiev MD, Morava E
Am J Hum Genet 2018 Apr 5;102(4):685-695. Epub 2018 Mar 22 doi: 10.1016/j.ajhg.2018.02.012. PMID: 29576219Free PMC Article
Hughey CC, Ma L, James FD, Bracy DP, Wang Z, Wasserman DH, Rottman JN, Hittel DS, Shearer J
Cardiovasc Diabetol 2013 Sep 4;12:128. doi: 10.1186/1475-2840-12-128. PMID: 24007410Free PMC Article
Smits P, Antonicka H, van Hasselt PM, Weraarpachai W, Haller W, Schreurs M, Venselaar H, Rodenburg RJ, Smeitink JA, van den Heuvel LP
Eur J Hum Genet 2011 Mar;19(3):275-9. Epub 2010 Dec 1 doi: 10.1038/ejhg.2010.208. PMID: 21119709Free PMC Article
Cízková A, Stránecký V, Ivánek R, Hartmannová H, Nosková L, Piherová L, Tesarová M, Hansíková H, Honzík T, Zeman J, Divina P, Potocká A, Paul J, Sperl W, Mayr JA, Seneca S, Houstĕk J, Kmoch S
BMC Genomics 2008 Jan 25;9:38. doi: 10.1186/1471-2164-9-38. PMID: 18221507Free PMC Article

Therapy

Dias HF, Kühtreiber WM, Nelson KJ, Ng NC, Zheng H, Faustman DL
Vaccine 2022 Mar 8;40(11):1540-1554. Epub 2021 Apr 28 doi: 10.1016/j.vaccine.2021.04.011. PMID: 33933315

Prognosis

Smits P, Saada A, Wortmann SB, Heister AJ, Brink M, Pfundt R, Miller C, Haas D, Hantschmann R, Rodenburg RJ, Smeitink JA, van den Heuvel LP
Eur J Hum Genet 2011 Apr;19(4):394-9. Epub 2010 Dec 29 doi: 10.1038/ejhg.2010.214. PMID: 21189481Free PMC Article
Smits P, Antonicka H, van Hasselt PM, Weraarpachai W, Haller W, Schreurs M, Venselaar H, Rodenburg RJ, Smeitink JA, van den Heuvel LP
Eur J Hum Genet 2011 Mar;19(3):275-9. Epub 2010 Dec 1 doi: 10.1038/ejhg.2010.208. PMID: 21119709Free PMC Article

Clinical prediction guides

Dias HF, Kühtreiber WM, Nelson KJ, Ng NC, Zheng H, Faustman DL
Vaccine 2022 Mar 8;40(11):1540-1554. Epub 2021 Apr 28 doi: 10.1016/j.vaccine.2021.04.011. PMID: 33933315
Lake NJ, Webb BD, Stroud DA, Richman TR, Ruzzenente B, Compton AG, Mountford HS, Pulman J, Zangarelli C, Rio M, Boddaert N, Assouline Z, Sherpa MD, Schadt EE, Houten SM, Byrnes J, McCormick EM, Zolkipli-Cunningham Z, Haude K, Zhang Z, Retterer K, Bai R, Calvo SE, Mootha VK, Christodoulou J, Rötig A, Filipovska A, Cristian I, Falk MJ, Metodiev MD, Thorburn DR
Am J Hum Genet 2017 Aug 3;101(2):239-254. doi: 10.1016/j.ajhg.2017.07.005. PMID: 28777931Free PMC Article
Smits P, Saada A, Wortmann SB, Heister AJ, Brink M, Pfundt R, Miller C, Haas D, Hantschmann R, Rodenburg RJ, Smeitink JA, van den Heuvel LP
Eur J Hum Genet 2011 Apr;19(4):394-9. Epub 2010 Dec 29 doi: 10.1038/ejhg.2010.214. PMID: 21189481Free PMC Article
Smits P, Antonicka H, van Hasselt PM, Weraarpachai W, Haller W, Schreurs M, Venselaar H, Rodenburg RJ, Smeitink JA, van den Heuvel LP
Eur J Hum Genet 2011 Mar;19(3):275-9. Epub 2010 Dec 1 doi: 10.1038/ejhg.2010.208. PMID: 21119709Free PMC Article
Fontanesi F, Palmieri L, Scarcia P, Lodi T, Donnini C, Limongelli A, Tiranti V, Zeviani M, Ferrero I, Viola AM
Hum Mol Genet 2004 May 1;13(9):923-34. Epub 2004 Mar 11 doi: 10.1093/hmg/ddh108. PMID: 15016764

Recent systematic reviews

Dogan AE, Yuksel C, Du F, Chouinard VA, Öngür D
Neuropsychopharmacology 2018 Jul;43(8):1681-1690. Epub 2018 Mar 14 doi: 10.1038/s41386-018-0041-9. PMID: 29581538Free PMC Article

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