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Combined oxidative phosphorylation deficiency 58(COXPD58)

MedGen UID:
1841277
Concept ID:
C5830641
Disease or Syndrome
Synonym: COXPD58
 
Gene (location): TEFM (17q11.2)
 
Monarch Initiative: MONDO:0957537
OMIM®: 620451

Definition

Combined oxidative phosphorylation deficiency-58 (COXPD58) is an autosomal recessive disorder characterized by a wide range of clinical presentations including neonatal lactic acidosis, epileptic encephalopathy, developmental delay and impaired intellectual development with nonspecific changes on brain MRI, or mitochondrial myopathy with a treatable neuromuscular transmission defect (Van Haute et al., 2023). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). [from OMIM]

Clinical features

From HPO
Lacticaciduria
MedGen UID:
871116
Concept ID:
C4025585
Finding
An increased concentration of lactic acid in the urine.
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.
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.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Epilepsia partialis continua
MedGen UID:
39303
Concept ID:
C0085543
Disease or Syndrome
Epilepsia partialis continua (also called Kojevnikov's or Kozhevnikov's epilepsia) is a type of focal motor status epilepticus characterized by repeated stereotyped simple motor manifestations such as jerks, typically of a limb or the face, recurring every few seconds or minutes for extended periods (days or years).
CNS demyelination
MedGen UID:
137898
Concept ID:
C0338474
Disease or Syndrome
A loss of myelin from nerve fibers in the central nervous system.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
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.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Exaggerated startle response
MedGen UID:
329357
Concept ID:
C1740801
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
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).
Appendicular spasticity
MedGen UID:
937224
Concept ID:
C4313257
Finding
A type of spasticity that affects one or more limbs (arms or legs).
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Ragged-red muscle fibers
MedGen UID:
477048
Concept ID:
C3275417
Finding
An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm.
EMG: decremental response of compound muscle action potential to repetitive nerve stimulation
MedGen UID:
892749
Concept ID:
C4021728
Finding
A compound muscle action potential (CMAP) is a type of electromyography (EMG). CMAP refers to a group of almost simultaneous action potentials from several muscle fibers in the same area evoked by stimulation of the supplying motor nerve and are recorded as one multipeaked summated action potential. This abnormality refers to a greater than normal decrease in the amplitude during the course of the investigation.
Appendicular hypotonia
MedGen UID:
868520
Concept ID:
C4022919
Finding
Muscular hypotonia of one or more limbs.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Respiratory failure requiring assisted ventilation
MedGen UID:
870821
Concept ID:
C4025279
Finding
A state of respiratory distress that requires a life saving intervention in the form of gaining airway access and instituting positive pressure ventilation.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Hyperprolinemia
MedGen UID:
75690
Concept ID:
C0268528
Disease or Syndrome
An increased concentration of proline in the blood.
Hyper-beta-alaninemia
MedGen UID:
75702
Concept ID:
C0268630
Disease or Syndrome
An increased concentration of alanine in the blood.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.
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).
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Low insertion of columella
MedGen UID:
866874
Concept ID:
C4021229
Finding
Insertion of the posterior columella below the nasal base.
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).
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.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Ophthalmoparesis
MedGen UID:
155551
Concept ID:
C0751401
Sign or Symptom
Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement.
Visual loss
MedGen UID:
784038
Concept ID:
C3665386
Finding
Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that).
Visual fixation instability
MedGen UID:
1372887
Concept ID:
C4476760
Finding
A deficit in the ability to fixate eye movements in order to stabilize images on the retina
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 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.

Professional guidelines

PubMed

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
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
Hanisch F, Müller T, Muser A, Deschauer M, Zierz S
J Neurol 2006 Apr;253(4):417-23. Epub 2006 Apr 20 doi: 10.1007/s00415-006-0987-0. PMID: 16619117

Recent clinical studies

Etiology

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
Chang SH, Pai PY, Hsu CH, Marthandam Asokan S, Tsai BC, Weng WT, Kuo WW, Shih TC, Kao HC, Chen WS, Huang CY
Drug Chem Toxicol 2023 Nov;46(5):1044-1050. Epub 2022 Oct 10 doi: 10.1080/01480545.2022.2122984. PMID: 36216784
González MDM, Santos C, Alarcón C, Ramos A, Cos M, Catalano G, Acebes JJ, Aluja MP
Mitochondrion 2021 May;58:95-101. Epub 2021 Mar 4 doi: 10.1016/j.mito.2021.02.013. PMID: 33675980
Lee YM, He W, Liou YC
Cell Death Dis 2021 Jan 11;12(1):58. doi: 10.1038/s41419-020-03355-3. PMID: 33431811Free PMC Article
Poynter JN, Richardson M, Langer E, Hooten AJ, Roesler M, Hirsch B, Nguyen PL, Cioc A, Warlick E, Ross JA
Genes Chromosomes Cancer 2016 Sep;55(9):688-93. Epub 2016 Jun 21 doi: 10.1002/gcc.22370. PMID: 27121678Free PMC Article

Diagnosis

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
Turco EM, Giovenale AMG, Sireno L, Mazzoni M, Cammareri A, Marchioretti C, Goracci L, Di Veroli A, Marchesan E, D'Andrea D, Falconieri A, Torres B, Bernardini L, Magnifico MC, Paone A, Rinaldo S, Della Monica M, D'Arrigo S, Postorivo D, Nardone AM, Zampino G, Onesimo R, Leoni C, Caicci F, Raimondo D, Binda E, Trobiani L, De Jaco A, Tata AM, Ferrari D, Cutruzzolà F, Mazzoccoli G, Ziviani E, Pennuto M, Vescovi AL, Rosati J
Cell Death Dis 2022 Nov 21;13(11):981. doi: 10.1038/s41419-022-05410-7. PMID: 36411275Free PMC Article
González MDM, Santos C, Alarcón C, Ramos A, Cos M, Catalano G, Acebes JJ, Aluja MP
Mitochondrion 2021 May;58:95-101. Epub 2021 Mar 4 doi: 10.1016/j.mito.2021.02.013. PMID: 33675980
Chang T, Jung BK, Sohn WM, Hong S, Shin H, Ryoo S, Lee J, Lee KH, Khieu V, Huy R, Chai JY
Korean J Parasitol 2020 Dec;58(6):619-625. Epub 2020 Dec 29 doi: 10.3347/kjp.2020.58.6.619. PMID: 33412765Free PMC Article
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Therapy

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Stem Cell Res Ther 2023 Apr 1;14(1):58. doi: 10.1186/s13287-023-03278-8. PMID: 37005657Free PMC Article
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Phytother Res 2023 Feb;37(2):592-610. Epub 2022 Sep 30 doi: 10.1002/ptr.7637. PMID: 36180975
Staikou C, Stamelos M, Stavroulakis E
Anaesthesiol Intensive Ther 2019;51(2):133-146. doi: 10.5114/ait.2019.86278. PMID: 31268275
Egaña-Gorroño L, Martínez E, Domingo P, Loncà M, Escribà T, Fontdevila J, Vidal F, Negredo E, Gatell JM, Arnedo M
Antimicrob Agents Chemother 2014 Nov;58(11):6717-23. Epub 2014 Aug 25 doi: 10.1128/AAC.03481-14. PMID: 25155608Free PMC Article
Hulgan T, Tebas P, Canter JA, Mulligan K, Haas DW, Dubé M, Grinspoon S, Robbins GK, Motsinger AA, Kallianpur AR; AIDS Clinical Trials Group 384 and A5005s Study Teams
J Infect Dis 2008 Mar 15;197(6):858-66. doi: 10.1086/528697. PMID: 18419350

Prognosis

Zhang X, Xiang F, Li D, Yang F, Yu S, Wang X
BMC Neurol 2024 Jan 2;24(1):15. doi: 10.1186/s12883-023-03480-4. PMID: 38166857Free PMC Article
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J Pediatr Endocrinol Metab 2021 May 26;34(5):649-652. Epub 2021 Apr 7 doi: 10.1515/jpem-2020-0694. PMID: 33823107
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
Poynter JN, Richardson M, Langer E, Hooten AJ, Roesler M, Hirsch B, Nguyen PL, Cioc A, Warlick E, Ross JA
Genes Chromosomes Cancer 2016 Sep;55(9):688-93. Epub 2016 Jun 21 doi: 10.1002/gcc.22370. PMID: 27121678Free PMC Article
Alis R, Santos-Lozano A, Sanchis-Gomar F, Pareja-Galeano H, Fiuza-Luces C, Garatachea N, Lucia A, Emanuele E
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Clinical prediction guides

Kaludercic N, Arusei RJ, Di Lisa F
Basic Res Cardiol 2023 Oct 4;118(1):41. doi: 10.1007/s00395-023-01012-2. PMID: 37792081Free PMC Article
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
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
Alis R, Santos-Lozano A, Sanchis-Gomar F, Pareja-Galeano H, Fiuza-Luces C, Garatachea N, Lucia A, Emanuele E
J Trace Elem Med Biol 2016 May;35:103-6. Epub 2016 Feb 12 doi: 10.1016/j.jtemb.2016.02.002. PMID: 27049133
Hawash MB, Betson M, Al-Jubury A, Ketzis J, LeeWillingham A, Bertelsen MF, Cooper PJ, Littlewood DT, Zhu XQ, Nejsum P
Parasit Vectors 2016 Jan 22;9:37. doi: 10.1186/s13071-016-1325-8. PMID: 26800683Free PMC Article

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