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Combined oxidative phosphorylation deficiency 40(COXPD40)

MedGen UID:
1714731
Concept ID:
C5394232
Disease or Syndrome
Synonyms: COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 40; COXPD40
SNOMED CT: QRSL1-related combined oxidative phosphorylation defect (1197430005); Glutaminyl-transfer ribonucleic acid amidotransferase subunit-related combined oxidative phosphorylation defect (1197430005)
 
Gene (location): QRSL1 (6q21)
 
Monarch Initiative: MONDO:0030006
OMIM®: 618835
Orphanet: ORPHA570491

Definition

Combined oxidative phosphorylation deficiency-40 (COXPD40) is an autosomal recessive mitochondrial disorder with onset in utero or soon after birth. Affected individuals have severe hypertrophic cardiomyopathy, poor growth, and sensorineural hearing loss. Laboratory studies show evidence of mitochondrial dysfunction, such as lactic acidosis. Patient-derived tissues and cells show variably decreased activities of mitochondrial respiratory complexes I, III, IV, and V. The disorder is lethal, with no reported patients surviving past infancy (summary by Friederich et al., 2018). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). [from OMIM]

Clinical features

From HPO
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Decreased liver function
MedGen UID:
65430
Concept ID:
C0232744
Finding
Reduced ability of the liver to perform its functions.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Premature birth
MedGen UID:
57721
Concept ID:
C0151526
Pathologic Function
The birth of a baby of less than 37 weeks of gestational age.
Non-immune hydrops fetalis
MedGen UID:
105327
Concept ID:
C0455988
Disease or Syndrome
Hydrops fetalis is a descriptive term for generalized edema of the fetus, with fluid accumulation in extravascular components and body cavities. It is not a diagnosis in itself, but a symptom and end-stage result of a wide variety of disorders. In the case of immune hydrops fetalis, a frequent cause is maternofetal incompatibility as in that related to a number of genetic anemias and metabolic disorders expressed in the fetus; in other instances, it remains idiopathic and likely multifactorial (summary by Bellini et al., 2009). Nonimmune hydrops fetalis accounts for 76 to 87% of all described cases of hydrops fetalis (Bellini et al., 2009). Genetic Heterogeneity of Hydrops Fetalis In southeast Asia, alpha-thalassemia (604131) is the most common cause of hydrops fetalis, accounting for 60 to 90% of cases. Almost all of these cases result from homozygous deletion of the HBA1 (141800) and HBA2 (141850) genes. A few cases have been reported that had 1 apparently normal alpha-globin gene, termed the hemoglobin H (613978) hydrops fetalis syndrome (summary by Chui and Waye, 1998). Other genetic disorders predisposing to NIHF include other congenital anemias, such as erythropoietic porphyria (e.g., 606938.0013), and many metabolic disorders, such as one form of Gaucher disease (e.g., 606463.0009), infantile sialic acid storage disease (269920), mucopolysaccharidosis type VII (253220), glycogen storage disease IV (232500), congenital disorder of glycosylation type Ia (212065), and disorders of lymphatic malformation (see, e.g., LMPHM1, 153100).
Decreased circulating cortisol level
MedGen UID:
322961
Concept ID:
C1836623
Finding
Abnormally reduced concentration of cortisol in the blood.
Decreased activity of mitochondrial complex I
MedGen UID:
393796
Concept ID:
C2677650
Finding
A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria.
Decreased activity of mitochondrial complex III
MedGen UID:
460434
Concept ID:
C3149083
Finding
A reduction in the activity of the mitochondrial respiratory chain complex III, which is part of the electron transport chain in mitochondria.
Decreased activity of mitochondrial complex IV
MedGen UID:
866520
Concept ID:
C4020800
Finding
A reduction in the activity of the mitochondrial respiratory chain complex IV, which is part of the electron transport chain in mitochondria.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCombined oxidative phosphorylation deficiency 40

Professional guidelines

PubMed

Sato R, Vatic M, Peixoto da Fonseca GW, Anker SD, von Haehling S
Cardiovasc Res 2024 Jul 31;120(9):982-998. doi: 10.1093/cvr/cvae073. PMID: 38828887
Naftali J, Mermelstein M, Landau YE, Barnea R, Shelly S, Auriel E, Peretz S
Acta Neurol Belg 2023 Jun;123(3):1019-1028. Epub 2023 Feb 15 doi: 10.1007/s13760-023-02196-z. PMID: 36792807
Esmaeili Y, Yarjanli Z, Pakniya F, Bidram E, Łos MJ, Eshraghi M, Klionsky DJ, Ghavami S, Zarrabi A
J Control Release 2022 May;345:147-175. Epub 2022 Mar 3 doi: 10.1016/j.jconrel.2022.03.001. PMID: 35248646

Recent clinical studies

Therapy

Tarnawski J, Czub M, Dymecki M, Sunil M, Folwarski M
Nutrients 2024 Jun 25;16(13) doi: 10.3390/nu16132011. PMID: 38999759Free PMC Article
Zou L, Huang J, Zhang Q, Mo H, Xia W, Zhu C, Rao M
Hum Reprod 2023 Dec 4;38(12):2422-2432. doi: 10.1093/humrep/dead196. PMID: 37814907
Magalhães FC, Ferraresi C
Photobiomodul Photomed Laser Surg 2022 Sep;40(9):597-603. Epub 2022 Aug 30 doi: 10.1089/photob.2022.0031. PMID: 36040371
Kearney M, Orrell RW, Fahey M, Brassington R, Pandolfo M
Cochrane Database Syst Rev 2016 Aug 30;2016(8):CD007791. doi: 10.1002/14651858.CD007791.pub4. PMID: 27572719Free PMC Article
Beal MF
Amino Acids 2011 May;40(5):1305-13. Epub 2011 Mar 30 doi: 10.1007/s00726-011-0851-0. PMID: 21448659

Prognosis

Verma A, Lehman AN, Gokcan H, Cropcho L, Black D, Dobrowolski SF, Vockley J, Bedoyan JK
Mol Genet Genomic Med 2024 Jan;12(1):e2283. Epub 2023 Sep 8 doi: 10.1002/mgg3.2283. PMID: 37688338Free PMC Article
Gevezova M, Kazakova M, Trenova A, Sarafian V
Int J Mol Sci 2023 Nov 14;24(22) doi: 10.3390/ijms242216297. PMID: 38003487Free PMC Article
Spath K, Babariya D, Konstantinidis M, Lowndes J, Child T, Grifo JA, Poulton J, Wells D
Fertil Steril 2021 Jun;115(6):1521-1532. Epub 2021 Mar 19 doi: 10.1016/j.fertnstert.2021.01.026. PMID: 33745725
de Oliveira MAA, Mallmann NH, de Souza GKBB, de Jesus Bacha T, Lima ES, de Lima DSN, de Souza Passos LF, de Souza Gonçalves M, de Moura Neto JP
Clin Rheumatol 2021 Sep;40(9):3639-3649. Epub 2021 Mar 20 doi: 10.1007/s10067-021-05680-0. PMID: 33745084
Elstner M, Andreoli C, Ahting U, Tetko I, Klopstock T, Meitinger T, Prokisch H
Mol Biotechnol 2008 Nov;40(3):306-15. Epub 2008 Sep 9 doi: 10.1007/s12033-008-9100-5. PMID: 18780189

Clinical prediction guides

Gevezova M, Kazakova M, Trenova A, Sarafian V
Int J Mol Sci 2023 Nov 14;24(22) doi: 10.3390/ijms242216297. PMID: 38003487Free PMC Article
Macedo RCO, Santos HO, Tinsley GM, Reischak-Oliveira A
Clin Nutr ESPEN 2020 Dec;40:17-26. Epub 2020 Aug 23 doi: 10.1016/j.clnesp.2020.07.022. PMID: 33183532
Lenin R, Thomas SM, Gangaraju R
Curr Pharm Des 2018;24(40):4742-4754. doi: 10.2174/1381612825666190115122622. PMID: 30644342
Kearney M, Orrell RW, Fahey M, Brassington R, Pandolfo M
Cochrane Database Syst Rev 2016 Aug 30;2016(8):CD007791. doi: 10.1002/14651858.CD007791.pub4. PMID: 27572719Free PMC Article
Elstner M, Andreoli C, Ahting U, Tetko I, Klopstock T, Meitinger T, Prokisch H
Mol Biotechnol 2008 Nov;40(3):306-15. Epub 2008 Sep 9 doi: 10.1007/s12033-008-9100-5. PMID: 18780189

Recent systematic reviews

Kearney M, Orrell RW, Fahey M, Brassington R, Pandolfo M
Cochrane Database Syst Rev 2016 Aug 30;2016(8):CD007791. doi: 10.1002/14651858.CD007791.pub4. PMID: 27572719Free PMC Article

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