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Combined oxidative phosphorylation deficiency 32(COXPD32)

MedGen UID:
1617600
Concept ID:
C4540029
Disease or Syndrome
Synonym: COXPD32
 
Gene (location): MRPS34 (16p13.3)
 
Monarch Initiative: MONDO:0054654
OMIM®: 617664

Definition

Combined oxidative phosphorylation deficiency-32 is an autosomal recessive neurodegenerative disorder characterized by onset of delayed psychomotor development and developmental regression in infancy. Affected individuals have multiple variable symptoms, including poor or absent speech, inability to walk, and abnormal movements. Brain imaging shows T2-weighted abnormalities in the basal ganglia and brainstem consistent with Leigh syndrome (256000). Patient cells showed decreased activities of mitochondrial respiratory chain complexes, I, III, and IV, as well as impaired mitochondrial translation (summary by Lake et al., 2017). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). [from OMIM]

Clinical features

From HPO
Horseshoe kidney
MedGen UID:
65140
Concept ID:
C0221353
Congenital Abnormality
A connection of the right and left kidney by an isthmus of functioning renal parenchyma or fibrous tissue that crosses the midline.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
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.
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.
Sleep apnea
MedGen UID:
11458
Concept ID:
C0037315
Disease or Syndrome
An intermittent cessation of airflow at the mouth and nose during sleep is known as sleep apnea. Apneas that last at least 10 seconds are considered significant, but individuals with sleep apnea may experience apneas lasting from 20 seconds up to 2 or 3 minutes. Patients may have up to 15 events per hour of sleep.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
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).
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Increased CSF lactate
MedGen UID:
257904
Concept ID:
C1167918
Finding
Increased concentration of lactate in the cerebrospinal fluid.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Elevated brain lactate level by MRS
MedGen UID:
868368
Concept ID:
C4022762
Finding
An increase in the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS).
Joint contracture
MedGen UID:
3228
Concept ID:
C0009918
Anatomical Abnormality
A limitation in the passive range of motion of the elbow resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part.
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.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
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.
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).
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Exotropia
MedGen UID:
4613
Concept ID:
C0015310
Disease or Syndrome
A form of strabismus with one or both eyes deviated outward.
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.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Sharma S, Repnikova E, Noel-MacDonnell JR, LePichon JB
Clin Genet 2021 Dec;100(6):752-757. Epub 2021 Sep 16 doi: 10.1111/cge.14057. PMID: 34480364Free PMC Article
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
Dasarathy S
Curr Opin Gastroenterol 2016 May;32(3):159-65. doi: 10.1097/MOG.0000000000000261. PMID: 26974417Free PMC Article

Recent clinical studies

Etiology

Martens LG, Luo J, Wermer MJH, Willems van Dijk K, Hägg S, Grassmann F, Noordam R, van Heemst D
Atherosclerosis 2022 Aug;354:1-7. Epub 2022 Jun 19 doi: 10.1016/j.atherosclerosis.2022.06.1012. PMID: 35793595
Stenton SL, Prokisch H
EBioMedicine 2020 Jun;56:102784. Epub 2020 May 23 doi: 10.1016/j.ebiom.2020.102784. PMID: 32454403Free 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
Haug SJ, Wong RW, Day S, Choudhry N, Sneed S, Prasad P, Read S, McDonald RH, Agarwal A, Davis J, Sarraf D
Retina 2016 Dec;36 Suppl 1:S159-S167. doi: 10.1097/IAE.0000000000001267. PMID: 28005674
Goebel HH
J Child Neurol 1995 Nov;10(6):424-37. doi: 10.1177/088307389501000602. PMID: 8576551

Diagnosis

Martens LG, Luo J, Wermer MJH, Willems van Dijk K, Hägg S, Grassmann F, Noordam R, van Heemst D
Atherosclerosis 2022 Aug;354:1-7. Epub 2022 Jun 19 doi: 10.1016/j.atherosclerosis.2022.06.1012. PMID: 35793595
Stenton SL, Prokisch H
EBioMedicine 2020 Jun;56:102784. Epub 2020 May 23 doi: 10.1016/j.ebiom.2020.102784. PMID: 32454403Free 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
Dasarathy S
Curr Opin Gastroenterol 2016 May;32(3):159-65. doi: 10.1097/MOG.0000000000000261. PMID: 26974417Free PMC Article
Goebel HH
J Child Neurol 1995 Nov;10(6):424-37. doi: 10.1177/088307389501000602. PMID: 8576551

Therapy

Jin BR, Lim CY, Kim HJ, Lee M, An HJ
Redox Biol 2023 Sep;65:102816. Epub 2023 Jul 11 doi: 10.1016/j.redox.2023.102816. PMID: 37454529Free PMC Article
Martens LG, Luo J, Wermer MJH, Willems van Dijk K, Hägg S, Grassmann F, Noordam R, van Heemst D
Atherosclerosis 2022 Aug;354:1-7. Epub 2022 Jun 19 doi: 10.1016/j.atherosclerosis.2022.06.1012. PMID: 35793595
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
Maresch CC, Stute DC, Alves MG, Oliveira PF, de Kretser DM, Linn T
Hum Reprod Update 2018 Jan 1;24(1):86-105. doi: 10.1093/humupd/dmx033. PMID: 29136166
Haug SJ, Wong RW, Day S, Choudhry N, Sneed S, Prasad P, Read S, McDonald RH, Agarwal A, Davis J, Sarraf D
Retina 2016 Dec;36 Suppl 1:S159-S167. doi: 10.1097/IAE.0000000000001267. PMID: 28005674

Prognosis

Lim S, Kim JW, Targher G
Trends Endocrinol Metab 2021 Jul;32(7):500-514. Epub 2021 May 8 doi: 10.1016/j.tem.2021.04.008. PMID: 33975804
Mendham AE, Goedecke JH, Zeng Y, Larsen S, George C, Hauksson J, Fortuin-de Smidt MC, Chibalin AV, Olsson T, Chorell E
Diabetologia 2021 Jul;64(7):1642-1659. Epub 2021 Mar 26 doi: 10.1007/s00125-021-05430-6. PMID: 33770195Free PMC Article
Masingue M, Benoist JF, Roze E, Moussa F, Sedel F, Lubetzki C, Nadjar Y
J Neurol Sci 2019 Jan 15;396:112-118. Epub 2018 Nov 10 doi: 10.1016/j.jns.2018.11.014. PMID: 30448717
van Diemen CC, Kerstjens-Frederikse WS, Bergman KA, de Koning TJ, Sikkema-Raddatz B, van der Velde JK, Abbott KM, Herkert JC, Löhner K, Rump P, Meems-Veldhuis MT, Neerincx PBT, Jongbloed JDH, van Ravenswaaij-Arts CM, Swertz MA, Sinke RJ, van Langen IM, Wijmenga C
Pediatrics 2017 Oct;140(4) doi: 10.1542/peds.2016-2854. PMID: 28939701
Walker UA
J HIV Ther 2003 May;8(2):32-5. PMID: 12838162

Clinical prediction guides

Lim S, Kim JW, Targher G
Trends Endocrinol Metab 2021 Jul;32(7):500-514. Epub 2021 May 8 doi: 10.1016/j.tem.2021.04.008. PMID: 33975804
Rana P, Kogut S, Wen X, Akhlaghi F, Aleo MD
Chem Res Toxicol 2020 Jul 20;33(7):1780-1790. Epub 2020 May 8 doi: 10.1021/acs.chemrestox.0c00040. PMID: 32338883
Maresch CC, Stute DC, Alves MG, Oliveira PF, de Kretser DM, Linn T
Hum Reprod Update 2018 Jan 1;24(1):86-105. doi: 10.1093/humupd/dmx033. PMID: 29136166
Haug SJ, Wong RW, Day S, Choudhry N, Sneed S, Prasad P, Read S, McDonald RH, Agarwal A, Davis J, Sarraf D
Retina 2016 Dec;36 Suppl 1:S159-S167. doi: 10.1097/IAE.0000000000001267. PMID: 28005674
Walker UA
J HIV Ther 2003 May;8(2):32-5. PMID: 12838162

Recent systematic reviews

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
Maresch CC, Stute DC, Alves MG, Oliveira PF, de Kretser DM, Linn T
Hum Reprod Update 2018 Jan 1;24(1):86-105. doi: 10.1093/humupd/dmx033. PMID: 29136166

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