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Combined oxidative phosphorylation deficiency 28(COXPD28)

MedGen UID:
1800504
Concept ID:
C5569081
Disease or Syndrome
Synonym: COXPD28
SNOMED CT: COXPD28 - combined oxidative phosphorylation defect type 28 (1187640000); Neonatal severe cardiopulmonary failure due to mitochondrial methylation defect (1187640000); Combined oxidative phosphorylation defect type 28 (1187640000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SLC25A26 (3p14.1)
 
Monarch Initiative: MONDO:0014775
OMIM®: 616794
Orphanet: ORPHA466784

Definition

Combined oxidative phosphorylation deficiency-28 (COXPD28) is a complex autosomal recessive multisystem disorder associated with mitochondrial dysfunction. The phenotype is variable, but includes episodic metabolic decompensation beginning in infancy that can result in mild muscle weakness, cardiorespiratory insufficiency, developmental delay, or even death. Biochemical studies of patient tissues show variable mitochondrial defects, including decreased activities of respiratory chain enzymes (summary by Kishita et al., 2015). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). [from OMIM]

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Poor appetite
MedGen UID:
68562
Concept ID:
C0232462
Sign or Symptom
A reduced desire to eat.
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.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
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.
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.
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).
Severe lactic acidosis
MedGen UID:
374223
Concept ID:
C1839436
Finding
A severe form of lactic acidemia.
Increased serum pyruvate
MedGen UID:
376596
Concept ID:
C1849488
Finding
An increased concentration of pyruvate in the blood.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

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
Wilson EL, Metzakopian E
Cell Death Differ 2021 Jun;28(6):1804-1821. Epub 2020 Dec 17 doi: 10.1038/s41418-020-00705-8. PMID: 33335290Free PMC Article
Vidhya Annapoorni CS, Retnaswami CS, Mailankody P, Katragadda P, Pillai SK, Rangarajan A, Padmanabha H, Pendharkar H
Neurol India 2020 Mar-Apr;68(2):368-372. doi: 10.4103/0028-3886.280647. PMID: 32415012

Recent clinical studies

Diagnosis

Ji Y, Wang S, Cheng Y, Fang L, Zhao J, Gao L, Xu C
Gene 2021 Dec 15;804:145891. Epub 2021 Aug 8 doi: 10.1016/j.gene.2021.145891. PMID: 34375635

Prognosis

Ji Y, Wang S, Cheng Y, Fang L, Zhao J, Gao L, Xu C
Gene 2021 Dec 15;804:145891. Epub 2021 Aug 8 doi: 10.1016/j.gene.2021.145891. PMID: 34375635

Clinical prediction guides

Ji Y, Wang S, Cheng Y, Fang L, Zhao J, Gao L, Xu C
Gene 2021 Dec 15;804:145891. Epub 2021 Aug 8 doi: 10.1016/j.gene.2021.145891. PMID: 34375635

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