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Combined oxidative phosphorylation deficiency 34(COXPD34)

MedGen UID:
1631307
Concept ID:
C4693450
Disease or Syndrome
Synonyms: COXPD34; Syndromic sensorineural deafness due to combined oxidative phosphorylation defect
SNOMED CT: Syndromic sensorineural hearing loss due to COXPD (combined oxidative phosphorylation defect) (1260133007); Syndromic sensorineural deafness due to combined oxidative phosphorylation defect (1260133007); Syndromic sensorineural deafness due to COXPD (combined oxidative phosphorylation defect) (1260133007)
 
Gene (location): MRPS7 (17q25.1)
 
Monarch Initiative: MONDO:0054741
OMIM®: 617872

Definition

COXPD34 is an autosomal recessive disorder resulting from a defect in mitochondrial function. The phenotype is variable, but may include congenital sensorineural deafness, increased serum lactate, and hepatic and renal dysfunction. Neurologic function is relatively preserved (summary by Menezes et al., 2015). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). [from OMIM]

Clinical features

From HPO
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.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Congenital sensorineural hearing impairment
MedGen UID:
356101
Concept ID:
C1865866
Disease or Syndrome
A type of hearing impairment caused by an abnormal functionality of the cochlear nerve with congenital onset.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
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.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Increased blood urea nitrogen
MedGen UID:
760252
Concept ID:
C0151539
Finding
An increased amount of nitrogen in the form of urea in the blood.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.
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).
Elevated circulating thyroid-stimulating hormone concentration
MedGen UID:
108325
Concept ID:
C0586553
Finding
Increased concentration of thyroid-stimulating hormone (TSH) in the blood circulation.
Hypergonadotropic hypogonadism
MedGen UID:
184926
Concept ID:
C0948896
Disease or Syndrome
Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay.
Primary adrenal insufficiency
MedGen UID:
854614
Concept ID:
C3887896
Disease or Syndrome
Insufficient production of steroid hormones (primarily cortisol) by the adrenal glands as a result of a primary defect in the glands themselves.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Lin Y, Zhang W, Chen Z, Lin C, Lin W, Fu Q, Peng W, Chen D
J Pediatr Endocrinol Metab 2021 May 26;34(5):649-652. Epub 2021 Apr 7 doi: 10.1515/jpem-2020-0694. PMID: 33823107
Hernández-Breijo B, Monserrat J, Ramírez-Rubio S, Cuevas EP, Vara D, Díaz-Laviada I, Fernández-Moreno MD, Román ID, Gisbert JP, Guijarro LG
World J Gastroenterol 2011 Sep 14;17(34):3899-911. doi: 10.3748/wjg.v17.i34.3899. PMID: 22025878Free PMC Article
Messinger Y, Uckun FM
Leuk Lymphoma 1999 Aug;34(5-6):415-32. doi: 10.3109/10428199909058469. PMID: 10492065

Recent clinical studies

Etiology

Boy N, Mühlhausen C, Maier EM, Ballhausen D, Baumgartner MR, Beblo S, Burgard P, Chapman KA, Dobbelaere D, Heringer-Seifert J, Fleissner S, Grohmann-Held K, Hahn G, Harting I, Hoffmann GF, Jochum F, Karall D, Konstantopoulous V, Krawinkel MB, Lindner M, Märtner EMC, Nuoffer JM, Okun JG, Plecko B, Posset R, Sahm K, Scholl-Bürgi S, Thimm E, Walter M, Williams M, Vom Dahl S, Ziagaki A, Zschocke J, Kölker S
J Inherit Metab Dis 2023 May;46(3):482-519. Epub 2022 Nov 17 doi: 10.1002/jimd.12566. PMID: 36221165
Nguyen KD, Corben LA, Pathirana PN, Horne MK, Delatycki MB, Szmulewicz DJ
IEEE Trans Neural Syst Rehabil Eng 2020 Apr;28(4):924-933. Epub 2020 Mar 2 doi: 10.1109/TNSRE.2020.2977354. PMID: 32142448
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
Karaa A, Elsharkawi I, Clapp MA, Balcells C
Mitochondrion 2019 May;46:214-220. Epub 2018 Jul 7 doi: 10.1016/j.mito.2018.06.007. PMID: 29990538
Drummond NJ, Davies NO, Lovett JE, Miller MR, Cook G, Becker T, Becker CG, McPhail DB, Kunath T
Sci Rep 2017 Sep 19;7(1):11857. doi: 10.1038/s41598-017-12072-5. PMID: 28928373Free PMC Article

Diagnosis

Gavriilaki M, Chatzikyriakou E, Moschou M, Arnaoutoglou M, Sakellari I, Kimiskidis VK
Cerebellum 2024 Jun;23(3):1184-1203. Epub 2023 Oct 27 doi: 10.1007/s12311-023-01621-6. PMID: 37889470Free PMC Article
Boy N, Mühlhausen C, Maier EM, Ballhausen D, Baumgartner MR, Beblo S, Burgard P, Chapman KA, Dobbelaere D, Heringer-Seifert J, Fleissner S, Grohmann-Held K, Hahn G, Harting I, Hoffmann GF, Jochum F, Karall D, Konstantopoulous V, Krawinkel MB, Lindner M, Märtner EMC, Nuoffer JM, Okun JG, Plecko B, Posset R, Sahm K, Scholl-Bürgi S, Thimm E, Walter M, Williams M, Vom Dahl S, Ziagaki A, Zschocke J, Kölker S
J Inherit Metab Dis 2023 May;46(3):482-519. Epub 2022 Nov 17 doi: 10.1002/jimd.12566. PMID: 36221165
Nguyen KD, Corben LA, Pathirana PN, Horne MK, Delatycki MB, Szmulewicz DJ
IEEE Trans Neural Syst Rehabil Eng 2020 Apr;28(4):924-933. Epub 2020 Mar 2 doi: 10.1109/TNSRE.2020.2977354. PMID: 32142448
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
Koene S, Smeitink J
J Inherit Metab Dis 2011 Apr;34(2):315-25. Epub 2010 Jul 29 doi: 10.1007/s10545-010-9162-y. PMID: 20668944Free PMC Article

Therapy

Gavriilaki M, Chatzikyriakou E, Moschou M, Arnaoutoglou M, Sakellari I, Kimiskidis VK
Cerebellum 2024 Jun;23(3):1184-1203. Epub 2023 Oct 27 doi: 10.1007/s12311-023-01621-6. PMID: 37889470Free PMC Article
Sanmarco LM, Rone JM, Polonio CM, Fernandez Lahore G, Giovannoni F, Ferrara K, Gutierrez-Vazquez C, Li N, Sokolovska A, Plasencia A, Faust Akl C, Nanda P, Heck ES, Li Z, Lee HG, Chao CC, Rejano-Gordillo CM, Fonseca-Castro PH, Illouz T, Linnerbauer M, Kenison JE, Barilla RM, Farrenkopf D, Stevens NA, Piester G, Chung EN, Dailey L, Kuchroo VK, Hava D, Wheeler MA, Clish C, Nowarski R, Balsa E, Lora JM, Quintana FJ
Nature 2023 Aug;620(7975):881-889. Epub 2023 Aug 9 doi: 10.1038/s41586-023-06409-6. PMID: 37558878Free PMC Article
Mason AL
Best Pract Res Clin Gastroenterol 2018 Jun-Aug;34-35:27-39. Epub 2018 Jun 14 doi: 10.1016/j.bpg.2018.06.001. PMID: 30343707
Tözsér J
Ann N Y Acad Sci 2001 Nov;946:145-59. doi: 10.1111/j.1749-6632.2001.tb03909.x. PMID: 11762983
Bartlett K, Ghneim HK, Stirk HJ, Wastell H
J Inherit Metab Dis 1985;8 Suppl 1:46-52. doi: 10.1007/BF01800659. PMID: 2864473

Prognosis

Lin Y, Zhang W, Chen Z, Lin C, Lin W, Fu Q, Peng W, Chen D
J Pediatr Endocrinol Metab 2021 May 26;34(5):649-652. Epub 2021 Apr 7 doi: 10.1515/jpem-2020-0694. PMID: 33823107
Sharifi S, Pakdel A, Ebrahimie E, Aryan Y, Ghaderi Zefrehee M, Reecy JM
J Appl Genet 2019 Nov;60(3-4):367-373. Epub 2019 Jun 11 doi: 10.1007/s13353-019-00499-7. PMID: 31187384
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
Skladal D, Halliday J, Thorburn DR
Brain 2003 Aug;126(Pt 8):1905-12. Epub 2003 May 21 doi: 10.1093/brain/awg170. PMID: 12805096
Tözsér J
Ann N Y Acad Sci 2001 Nov;946:145-59. doi: 10.1111/j.1749-6632.2001.tb03909.x. PMID: 11762983

Clinical prediction guides

Gavriilaki M, Chatzikyriakou E, Moschou M, Arnaoutoglou M, Sakellari I, Kimiskidis VK
Cerebellum 2024 Jun;23(3):1184-1203. Epub 2023 Oct 27 doi: 10.1007/s12311-023-01621-6. PMID: 37889470Free PMC Article
Nguyen KD, Corben LA, Pathirana PN, Horne MK, Delatycki MB, Szmulewicz DJ
IEEE Trans Neural Syst Rehabil Eng 2020 Apr;28(4):924-933. Epub 2020 Mar 2 doi: 10.1109/TNSRE.2020.2977354. PMID: 32142448
Sharifi S, Pakdel A, Ebrahimie E, Aryan Y, Ghaderi Zefrehee M, Reecy JM
J Appl Genet 2019 Nov;60(3-4):367-373. Epub 2019 Jun 11 doi: 10.1007/s13353-019-00499-7. PMID: 31187384
Mason AL
Best Pract Res Clin Gastroenterol 2018 Jun-Aug;34-35:27-39. Epub 2018 Jun 14 doi: 10.1016/j.bpg.2018.06.001. PMID: 30343707
Drummond NJ, Davies NO, Lovett JE, Miller MR, Cook G, Becker T, Becker CG, McPhail DB, Kunath T
Sci Rep 2017 Sep 19;7(1):11857. doi: 10.1038/s41598-017-12072-5. PMID: 28928373Free PMC Article

Recent systematic reviews

Gavriilaki M, Chatzikyriakou E, Moschou M, Arnaoutoglou M, Sakellari I, Kimiskidis VK
Cerebellum 2024 Jun;23(3):1184-1203. Epub 2023 Oct 27 doi: 10.1007/s12311-023-01621-6. PMID: 37889470Free PMC Article
Chang X, Wu Y, Zhou J, Meng H, Zhang W, Guo J
Medicine (Baltimore) 2020 Jan;99(5):e18634. doi: 10.1097/MD.0000000000018634. PMID: 32000367Free 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
Breil M, Chariot P
Muscle Nerve 1999 Dec;22(12):1631-6. doi: 10.1002/(sici)1097-4598(199912)22:12<1631::aid-mus3>3.0.co;2-v. PMID: 10567074

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