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Hypotonia with lactic acidemia and hyperammonemia(COXPD5)

MedGen UID:
435972
Concept ID:
C2673642
Disease or Syndrome
Synonym: Combined oxidative phosphorylation deficiency 5
SNOMED CT: Combined oxidative phosphorylation defect type 5 (724279004); COXPD5 - combined oxidative phosphorylation defect 5 (724279004); Hypotonia with lactic acidemia and hyperammonemia (724279004)
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): MRPS22 (3q23)
 
Monarch Initiative: MONDO:0012718
OMIM®: 611719
Orphanet: ORPHA137908

Definition

This syndrome is characterized by severe hypotonia, lactic acidemia and congenital hyperammonemia. It has been described in three newborns born to consanguineous parents. Ultrasound examination during the 36th week of pregnancy revealed generalized edema. Hypertrophic cardiomyopathy and tubulopathy developed within the first week of life and the infants died within the first month. The activities of enzymes in the mitochondrial respiratory chain were reduced in the muscles of the patients. Mutations were identified in the MRPS22 gene on chromosome 3q23, encoding a mitochondrial ribosomal protein [from SNOMEDCT_US]

Clinical features

From HPO
Abnormal renal tubule morphology
MedGen UID:
867449
Concept ID:
C4021826
Anatomical Abnormality
An abnormality of the renal tubules.
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity.
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.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
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.
Leukoencephalopathy
MedGen UID:
78722
Concept ID:
C0270612
Disease or Syndrome
This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Spastic tetraplegia
MedGen UID:
98433
Concept ID:
C0426970
Disease or Syndrome
Spastic paralysis affecting all four limbs.
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.
Delayed myelination
MedGen UID:
224820
Concept ID:
C1277241
Finding
Delayed myelination.
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.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
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.
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.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
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).
Hyperammonemia
MedGen UID:
1802066
Concept ID:
C5574662
Laboratory or Test Result
An increased concentration of ammonia in the blood.
Redundant neck skin
MedGen UID:
374440
Concept ID:
C1840319
Finding
Excess skin around the neck, often lying in horizontal folds.
Fetal skin edema
MedGen UID:
1814189
Concept ID:
C5676611
Pathologic Function
A separation of skin in one or more regions of the body or even along the entire length of body wall (to a degree greater than gestational-age related norms) related to pathologically increased fluid accumulation in the subcutaneous tissue.
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 Hypotonia with lactic acidemia and hyperammonemia in Orphanet.

Recent clinical studies

Diagnosis

Yen TY, Hwu WL, Chien YH, Wu MH, Lin MT, Tsao LY, Hsieh WS, Lee NC
Eur J Pediatr 2008 Aug;167(8):941-4. Epub 2007 Sep 11 doi: 10.1007/s00431-007-0592-y. PMID: 17846786
Briones P, Vilaseca MA, Ribes A, Vernet A, Lluch M, Cusi V, Huckriede A, Agsteribbe E
J Inherit Metab Dis 1997 Aug;20(4):569-77. doi: 10.1023/a:1005303008439. PMID: 9266394

Prognosis

Briones P, Vilaseca MA, Ribes A, Vernet A, Lluch M, Cusi V, Huckriede A, Agsteribbe E
J Inherit Metab Dis 1997 Aug;20(4):569-77. doi: 10.1023/a:1005303008439. PMID: 9266394

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