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Combined oxidative phosphorylation deficiency 52(COXPD52)

MedGen UID:
1780479
Concept ID:
C5543592
Disease or Syndrome
Synonyms: COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 52; COXPD52
 
Gene (location): NFS1 (20q11.22)
 
Monarch Initiative: MONDO:0030311
OMIM®: 619386

Definition

Combined oxidative phosphorylation deficiency-52 (COXPD52) is an autosomal recessive infantile mitochondrial complex II/III deficiency characterized by lactic acidemia, multiorgan system failure, and abnormal mitochondria. Intrafamilial variability has been reported (Farhan et al., 2014; Hershkovitz et al., 2021). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). [from OMIM]

Clinical features

From HPO
Aminoaciduria
MedGen UID:
116067
Concept ID:
C0238621
Disease or Syndrome
An increased concentration of an amino acid in the urine.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Lacticaciduria
MedGen UID:
871116
Concept ID:
C4025585
Finding
An increased concentration of lactic acid in the urine.
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.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Anorexia
MedGen UID:
315
Concept ID:
C0003123
Disease or Syndrome
Anorexia, or the loss of appetite for food, is a medical condition.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of disinterest, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Disseminated intravascular coagulation
MedGen UID:
41620
Concept ID:
C0012739
Disease or Syndrome
Disseminated intravascular coagulation is characterized by the widespread activation of coagulation, which results in the intravascular formation of fibrin and ultimately thrombotic occlusion of small and midsize vessels.
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.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
Pancreatitis
MedGen UID:
14586
Concept ID:
C0030305
Disease or Syndrome
The presence of inflammation in the pancreas.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
An abnormally high concentration in the circulation of aspartate aminotransferase (AST).
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
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.
Hyperglycinemia
MedGen UID:
82817
Concept ID:
C0268559
Disease or Syndrome
An elevated concentration of glycine in the blood.
Hyper-beta-alaninemia
MedGen UID:
75702
Concept ID:
C0268630
Disease or Syndrome
An increased concentration of alanine in the blood.
Hyperamylasemia
MedGen UID:
105401
Concept ID:
C0476327
Finding
Increased level of amylase in the blood, an enzyme which helps digest glycogen and starch. It is produced mainly in the pancreas and salivary glands.
Increased serum lactate
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).
Adrenal insufficiency
MedGen UID:
1351
Concept ID:
C0001623
Disease or Syndrome
Insufficient production of steroid hormones (primarily cortisol) by the adrenal glands.
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 II
MedGen UID:
892305
Concept ID:
C4024705
Finding
A reduction in the activity of the mitochondrial respiratory chain complex II, which is part of the electron transport chain in mitochondria.

Professional guidelines

PubMed

García-Otero L, López M, Guitart-Mampel M, Morén C, Goncé A, Esteve C, Salazar L, Gómez O, Martínez JM, Torres B, César S, Garrabou G, Crispi F, Gratacós E
PLoS One 2019;14(3):e0213279. Epub 2019 Mar 4 doi: 10.1371/journal.pone.0213279. PMID: 30830946Free PMC Article
Honzik T, Tesarova M, Magner M, Mayr J, Jesina P, Vesela K, Wenchich L, Szentivanyi K, Hansikova H, Sperl W, Zeman J
J Inherit Metab Dis 2012 Sep;35(5):749-59. Epub 2012 Jan 10 doi: 10.1007/s10545-011-9440-3. PMID: 22231385
Stacpoole PW, Kurtz TL, Han Z, Langaee T
Adv Drug Deliv Rev 2008 Oct-Nov;60(13-14):1478-87. Epub 2008 Jul 4 doi: 10.1016/j.addr.2008.02.014. PMID: 18647626Free PMC Article

Recent clinical studies

Etiology

Masoumi-Ardakani Y, Najafipour H, Nasri HR, Aminizadeh S, Jafari S, Moflehi D
Biomed Res Int 2022;2022:8720661. Epub 2022 Jan 13 doi: 10.1155/2022/8720661. PMID: 35071600Free PMC Article
Kanbay M, Copur S, Demiray A, Sag AA, Covic A, Ortiz A, Tuttle KR
Eur J Clin Invest 2022 Jun;52(6):e13748. Epub 2022 Jan 24 doi: 10.1111/eci.13748. PMID: 35040119
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
Shurtleff H, Barry D, Chanprasert S, Firman T, Warner M, Saneto RP
Epilepsy Behav 2018 Nov;88:235-243. Epub 2018 Oct 11 doi: 10.1016/j.yebeh.2018.09.013. PMID: 30316150
O'Byrne JJ, Tarailo-Graovac M, Ghani A, Champion M, Deshpande C, Dursun A, Ozgul RK, Freisinger P, Garber I, Haack TB, Horvath R, Barić I, Husain RA, Kluijtmans LAJ, Kotzaeridou U, Morris AA, Ross CJ, Santra S, Smeitink J, Tarnopolsky M, Wortmann SB, Mayr JA, Brunner-Krainz M, Prokisch H, Wasserman WW, Wevers RA, Engelke UF, Rodenburg RJ, Ting TW, McFarland R, Taylor RW, Salvarinova R, van Karnebeek CDM
Mol Genet Metab 2018 Jan;123(1):28-42. Epub 2017 Nov 15 doi: 10.1016/j.ymgme.2017.11.003. PMID: 29331171Free PMC Article

Diagnosis

Kanbay M, Copur S, Demiray A, Sag AA, Covic A, Ortiz A, Tuttle KR
Eur J Clin Invest 2022 Jun;52(6):e13748. Epub 2022 Jan 24 doi: 10.1111/eci.13748. PMID: 35040119
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
Shurtleff H, Barry D, Chanprasert S, Firman T, Warner M, Saneto RP
Epilepsy Behav 2018 Nov;88:235-243. Epub 2018 Oct 11 doi: 10.1016/j.yebeh.2018.09.013. PMID: 30316150
O'Byrne JJ, Tarailo-Graovac M, Ghani A, Champion M, Deshpande C, Dursun A, Ozgul RK, Freisinger P, Garber I, Haack TB, Horvath R, Barić I, Husain RA, Kluijtmans LAJ, Kotzaeridou U, Morris AA, Ross CJ, Santra S, Smeitink J, Tarnopolsky M, Wortmann SB, Mayr JA, Brunner-Krainz M, Prokisch H, Wasserman WW, Wevers RA, Engelke UF, Rodenburg RJ, Ting TW, McFarland R, Taylor RW, Salvarinova R, van Karnebeek CDM
Mol Genet Metab 2018 Jan;123(1):28-42. Epub 2017 Nov 15 doi: 10.1016/j.ymgme.2017.11.003. PMID: 29331171Free PMC Article
Anglin RE, Garside SL, Tarnopolsky MA, Mazurek MF, Rosebush PI
J Clin Psychiatry 2012 Apr;73(4):506-12. doi: 10.4088/JCP.11r07237. PMID: 22579150

Therapy

Masoumi-Ardakani Y, Najafipour H, Nasri HR, Aminizadeh S, Jafari S, Moflehi D
Biomed Res Int 2022;2022:8720661. Epub 2022 Jan 13 doi: 10.1155/2022/8720661. PMID: 35071600Free 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
Sun X, Jiang G, Ju X, Fu H
Medicine (Baltimore) 2018 Dec;97(52):e13866. doi: 10.1097/MD.0000000000013866. PMID: 30593190Free PMC Article
Joshi N, Biswas J, Nath C, Singh S
Mol Neurobiol 2015 Aug;52(1):330-40. Epub 2014 Aug 27 doi: 10.1007/s12035-014-8865-8. PMID: 25159482
Stacpoole PW, Kurtz TL, Han Z, Langaee T
Adv Drug Deliv Rev 2008 Oct-Nov;60(13-14):1478-87. Epub 2008 Jul 4 doi: 10.1016/j.addr.2008.02.014. PMID: 18647626Free PMC Article

Prognosis

Biousse V, Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Vignal-Clermont C, Klopstock T, Sadun AA, Sergott RC, Hage R, Esposti S, La Morgia C, Priglinger C, Karanja R, Blouin L, Taiel M, Sahel JA; LHON Study Group
J Neuroophthalmol 2021 Sep 1;41(3):309-315. doi: 10.1097/WNO.0000000000001367. PMID: 34415265Free PMC Article
Pilli T, Dalmazio G, Porcelli B, Cantara S, Tabucchi A, Pini A, Spreafico A, Cartocci A, Forleo R, Pacini F, Scapellato C, Castagna MG
Thyroid 2021 Sep;31(9):1416-1423. Epub 2021 Aug 19 doi: 10.1089/thy.2021.0170. PMID: 34281356
Legrand L, Diallo A, Monin ML, Ewenczyk C, Charles P, Isnard R, Vicaut E, Montalescot G, Durr A, Pousset F
Am J Cardiovasc Drugs 2020 Apr;20(2):209-216. doi: 10.1007/s40256-019-00375-z. PMID: 31650522
Delp J, Funke M, Rudolf F, Cediel A, Bennekou SH, van der Stel W, Carta G, Jennings P, Toma C, Gardner I, van de Water B, Forsby A, Leist M
Arch Toxicol 2019 Jun;93(6):1585-1608. Epub 2019 Jun 12 doi: 10.1007/s00204-019-02473-y. PMID: 31190196
Mühlhausen C, Salomons GS, Lukacs Z, Struys EA, van der Knaap MS, Ullrich K, Santer R
J Inherit Metab Dis 2014 Sep;37(5):775-81. Epub 2014 Apr 1 doi: 10.1007/s10545-014-9702-y. PMID: 24687295

Clinical prediction guides

Delp J, Funke M, Rudolf F, Cediel A, Bennekou SH, van der Stel W, Carta G, Jennings P, Toma C, Gardner I, van de Water B, Forsby A, Leist M
Arch Toxicol 2019 Jun;93(6):1585-1608. Epub 2019 Jun 12 doi: 10.1007/s00204-019-02473-y. PMID: 31190196
Shurtleff H, Barry D, Chanprasert S, Firman T, Warner M, Saneto RP
Epilepsy Behav 2018 Nov;88:235-243. Epub 2018 Oct 11 doi: 10.1016/j.yebeh.2018.09.013. PMID: 30316150
O'Byrne JJ, Tarailo-Graovac M, Ghani A, Champion M, Deshpande C, Dursun A, Ozgul RK, Freisinger P, Garber I, Haack TB, Horvath R, Barić I, Husain RA, Kluijtmans LAJ, Kotzaeridou U, Morris AA, Ross CJ, Santra S, Smeitink J, Tarnopolsky M, Wortmann SB, Mayr JA, Brunner-Krainz M, Prokisch H, Wasserman WW, Wevers RA, Engelke UF, Rodenburg RJ, Ting TW, McFarland R, Taylor RW, Salvarinova R, van Karnebeek CDM
Mol Genet Metab 2018 Jan;123(1):28-42. Epub 2017 Nov 15 doi: 10.1016/j.ymgme.2017.11.003. PMID: 29331171Free PMC Article
Joshi N, Biswas J, Nath C, Singh S
Mol Neurobiol 2015 Aug;52(1):330-40. Epub 2014 Aug 27 doi: 10.1007/s12035-014-8865-8. PMID: 25159482
Mühlhausen C, Salomons GS, Lukacs Z, Struys EA, van der Knaap MS, Ullrich K, Santer R
J Inherit Metab Dis 2014 Sep;37(5):775-81. Epub 2014 Apr 1 doi: 10.1007/s10545-014-9702-y. PMID: 24687295

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

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