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Combined oxidative phosphorylation defect type 2(COXPD2)

MedGen UID:
400626
Concept ID:
C1864843
Disease or Syndrome
Synonyms: Combined oxidative phosphorylation deficiency 2; CORPUS CALLOSUM, AGENESIS OF, WITH DYSMORPHISM AND FATAL LACTIC ACIDOSIS
SNOMED CT: Combined oxidative phosphorylation defect type 2 (764943000); COXPD2 - combined oxidative phosphorylation defect type 2 (764943000)
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): MRPS16 (10q22.2)
 
Monarch Initiative: MONDO:0012510
OMIM®: 610498
Orphanet: ORPHA254920

Definition

A rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterized by severe intrauterine growth retardation, neonatal limb edema and redundant skin on the neck (hydrops), developmental brain defects (corpus callosum agenesis, ventriculomegaly), brachydactyly, dysmorphic facial features with low set ears, severe intractable neonatal lactic acidosis with lethargy, hypotonia, absent spontaneous movements and fatal outcome. Markedly decreased activity of complex I, II + III and IV in muscle and liver have been determined. [from SNOMEDCT_US]

Clinical features

From HPO
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
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.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of disinterest, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
Hypokinesia
MedGen UID:
39223
Concept ID:
C0086439
Finding
Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
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.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Elevated hepatic transaminase
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Redundant neck skin
MedGen UID:
374440
Concept ID:
C1840319
Finding
Excess skin around the neck, often lying in horizontal folds.
Mild fetal ventriculomegaly
MedGen UID:
869206
Concept ID:
C4023628
Anatomical Abnormality
A kind of ventriculomegaly occurring in the fetal period and usually diagnosed by prenatal ultrasound. Cerebral ventriculomegaly is defined by atrial measurements 10 mm or more. Mild ventriculomegaly (MVM) is defined as measurements between 10 and 15 mm. Measurements are obtained from an axial plane at the level of the thalamic nuclei just below the standard image to measure the BPD (PMID:16100637).
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 III
MedGen UID:
460434
Concept ID:
C3149083
Finding
A reduction in the activity of the mitochondrial respiratory chain complex III, 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.
Decreased activity of mitochondrial ATP synthase complex
MedGen UID:
892442
Concept ID:
C4023125
Finding
A reduction in the activity of the mitochondrial proton-transporting ATP synthase complex, which makes ATP via oxidative phosphorylation, and is sometimes described as Complex V of the electron transport chain.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Combined oxidative phosphorylation defect type 2 in Orphanet.

Professional guidelines

PubMed

Woodman RJ, Chew GT, Watts GF
Drugs 2005;65(1):31-74. doi: 10.2165/00003495-200565010-00003. PMID: 15610050

Recent clinical studies

Etiology

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Drugs 2005;65(1):31-74. doi: 10.2165/00003495-200565010-00003. PMID: 15610050

Diagnosis

Zhang Q, Ouyang Q, Xiang J, Li H, Lv H, An Y
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Lewis SF, Haller RG
J Appl Physiol (1985) 1986 Aug;61(2):391-401. doi: 10.1152/jappl.1986.61.2.391. PMID: 3528113

Therapy

Dias HF, Kühtreiber WM, Nelson KJ, Ng NC, Zheng H, Faustman DL
Vaccine 2022 Mar 8;40(11):1540-1554. Epub 2021 Apr 28 doi: 10.1016/j.vaccine.2021.04.011. PMID: 33933315
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Prognosis

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J Pediatr 2007 Apr;150(4):407-11. doi: 10.1016/j.jpeds.2006.12.047. PMID: 17382120
Woodman RJ, Chew GT, Watts GF
Drugs 2005;65(1):31-74. doi: 10.2165/00003495-200565010-00003. PMID: 15610050
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N Engl J Med 2004 Feb 12;350(7):664-71. doi: 10.1056/NEJMoa031314. PMID: 14960743Free PMC Article

Clinical prediction guides

Zhang Q, Ouyang Q, Xiang J, Li H, Lv H, An Y
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