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Mitochondrial complex 1 deficiency, nuclear type 9(MC1DN9)

MedGen UID:
1648447
Concept ID:
C4748767
Disease or Syndrome
Synonym: MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 9
 
Gene (location): NDUFS6 (5p15.33)
 
Monarch Initiative: MONDO:0032615
OMIM®: 618232

Clinical features

From HPO
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.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.
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.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Severe muscular hypotonia
MedGen UID:
326544
Concept ID:
C1839630
Finding
A severe degree of muscular hypotonia characterized by markedly reduced muscle tone.
Hypoventilation
MedGen UID:
469022
Concept ID:
C3203358
Pathologic Function
A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide).
Breathing dysregulation
MedGen UID:
814376
Concept ID:
C3808046
Finding
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.
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.
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.

Recent clinical studies

Etiology

Gurubaran IS
Acta Ophthalmol 2024 Mar;102 Suppl 282:3-53. doi: 10.1111/aos.16661. PMID: 38467968
Clément V, Dunand-Sauthier I, Wiznerowicz M, Clarkson SG
DNA Repair (Amst) 2007 May 1;6(5):602-14. Epub 2007 Jan 5 doi: 10.1016/j.dnarep.2006.11.010. PMID: 17208056
Silva JP, Köhler M, Graff C, Oldfors A, Magnuson MA, Berggren PO, Larsson NG
Nat Genet 2000 Nov;26(3):336-40. doi: 10.1038/81649. PMID: 11062475

Diagnosis

Pulman J, Ruzzenente B, Bianchi L, Rio M, Boddaert N, Munnich A, Rötig A, Metodiev MD
Hum Mol Genet 2019 May 1;28(9):1445-1462. doi: 10.1093/hmg/ddy441. PMID: 30566640
Hallmann K, Kudin AP, Zsurka G, Kornblum C, Reimann J, Stüve B, Waltz S, Hattingen E, Thiele H, Nürnberg P, Rüb C, Voos W, Kopatz J, Neumann H, Kunz WS
Brain 2016 Feb;139(Pt 2):338-45. Epub 2015 Dec 17 doi: 10.1093/brain/awv357. PMID: 26685157
Tucker EJ, Compton AG, Calvo SE, Thorburn DR
IUBMB Life 2011 Sep;63(9):669-77. Epub 2011 Jul 15 doi: 10.1002/iub.495. PMID: 21766414

Therapy

Liu ML, Scalia R, Mehta JL, Williams KJ
Arterioscler Thromb Vasc Biol 2012 Sep;32(9):2113-21. Epub 2012 Jul 19 doi: 10.1161/ATVBAHA.112.255471. PMID: 22814745Free PMC Article

Prognosis

Hallmann K, Kudin AP, Zsurka G, Kornblum C, Reimann J, Stüve B, Waltz S, Hattingen E, Thiele H, Nürnberg P, Rüb C, Voos W, Kopatz J, Neumann H, Kunz WS
Brain 2016 Feb;139(Pt 2):338-45. Epub 2015 Dec 17 doi: 10.1093/brain/awv357. PMID: 26685157

Clinical prediction guides

Gurubaran IS
Acta Ophthalmol 2024 Mar;102 Suppl 282:3-53. doi: 10.1111/aos.16661. PMID: 38467968
Silva JP, Köhler M, Graff C, Oldfors A, Magnuson MA, Berggren PO, Larsson NG
Nat Genet 2000 Nov;26(3):336-40. doi: 10.1038/81649. PMID: 11062475

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