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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). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	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.

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Fatigue

MedGen UID:: 41971
•Concept ID:: C0015672
•: Sign or Symptom

A subjective feeling of tiredness characterized by a lack of energy and motivation.

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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.

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Poor appetite

MedGen UID:: 68562
•Concept ID:: C0232462
•: Sign or Symptom

A reduced desire to eat.

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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.

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Muscle weakness

MedGen UID:: 57735
•Concept ID:: C0151786
•: Finding

Reduced strength of muscles.

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Generalized hypotonia

MedGen UID:: 346841
•Concept ID:: C1858120
•: Finding

Generalized muscular hypotonia (abnormally low muscle tone).

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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.

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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.

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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).

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Severe lactic acidosis

MedGen UID:: 374223
•Concept ID:: C1839436
•: Finding

A severe form of lactic acidemia.

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Increased serum pyruvate

MedGen UID:: 376596
•Concept ID:: C1849488
•: Finding

An increased concentration of pyruvate in the blood.

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Polyhydramnios

MedGen UID:: 6936
•Concept ID:: C0020224
•: Pathologic Function

The presence of excess amniotic fluid in the uterus during pregnancy.

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Decreased fetal movement

MedGen UID:: 68618
•Concept ID:: C0235659
•: Finding

An abnormal reduction in quantity or strength of fetal movements.

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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.

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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.

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Abnormal cellular phenotype
- Decreased activity of mitochondrial complex I
- Decreased activity of mitochondrial complex IV
Abnormality of metabolism/homeostasis
Abnormality of prenatal development or birth
- Decreased fetal movement
- Polyhydramnios
Abnormality of the cardiovascular system
- Congestive heart failure
Abnormality of the digestive system
- Poor appetite
Abnormality of the musculoskeletal system
Abnormality of the nervous system
- Global developmental delay
Abnormality of the respiratory system
- Respiratory failure
Constitutional symptom
- Abdominal pain
- Fatigue

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVCombined oxidative phosphorylation deficiency

Combined oxidative phosphorylation deficiency
- Combined oxidative phosphorylation deficiency 28

Professional guidelines

PubMed

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Antimyoclonic Effect of Levetiracetam and Clonazepam Combined Treatment on Myoclonic Epilepsy with Ragged-Red Fiber Syndrome with m.8344A>G Mutation.

Su LJ, Wang YL, Han T, Qiao S, Zang KJ, Wu HK, Su YX, Liu LL, Liu XW
Chin Med J (Engl) 2018 Oct 20;131(20):2433-2438. doi: 10.4103/0366-6999.243568. PMID: 30334528 Free PMC Article

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