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Mitochondrial complex 1 deficiency, nuclear type 3(MC1DN3)

MedGen UID:
1648346
Concept ID:
C4748752
Disease or Syndrome
Synonym: MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 3
 
Gene (location): NDUFS7 (19p13.3)
 
Monarch Initiative: MONDO:0032608
OMIM®: 618224

Clinical features

From HPO
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
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.
Episodic vomiting
MedGen UID:
333228
Concept ID:
C1838993
Finding
Paroxysmal, recurrent episodes of vomiting.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
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.
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Abnormal pyramidal sign
MedGen UID:
68582
Concept ID:
C0234132
Sign or Symptom
Functional neurological abnormalities related to dysfunction of the pyramidal tract.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
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.

Recent clinical studies

Etiology

Gurubaran IS
Acta Ophthalmol 2024 Mar;102 Suppl 282:3-53. doi: 10.1111/aos.16661. PMID: 38467968
Hipps D, Dobson PF, Warren C, McDonald D, Fuller A, Filby A, Bulmer D, Laude A, Russell O, Deehan DJ, Turnbull DM, Lawless C
Bone 2022 May;158:116371. Epub 2022 Feb 19 doi: 10.1016/j.bone.2022.116371. PMID: 35192969
Feichtinger RG, Oláhová M, Kishita Y, Garone C, Kremer LS, Yagi M, Uchiumi T, Jourdain AA, Thompson K, D'Souza AR, Kopajtich R, Alston CL, Koch J, Sperl W, Mastantuono E, Strom TM, Wortmann SB, Meitinger T, Pierre G, Chinnery PF, Chrzanowska-Lightowlers ZM, Lightowlers RN, DiMauro S, Calvo SE, Mootha VK, Moggio M, Sciacco M, Comi GP, Ronchi D, Murayama K, Ohtake A, Rebelo-Guiomar P, Kohda M, Kang D, Mayr JA, Taylor RW, Okazaki Y, Minczuk M, Prokisch H
Am J Hum Genet 2017 Oct 5;101(4):525-538. Epub 2017 Sep 21 doi: 10.1016/j.ajhg.2017.08.015. PMID: 28942965Free PMC Article
Salminen A, Kaarniranta K, Kauppinen A, Ojala J, Haapasalo A, Soininen H, Hiltunen M
Prog Neurobiol 2013 Jul-Aug;106-107:33-54. Epub 2013 Jul 1 doi: 10.1016/j.pneurobio.2013.06.002. PMID: 23827971
Ritov VB, Menshikova EV, Azuma K, Wood R, Toledo FG, Goodpaster BH, Ruderman NB, Kelley DE
Am J Physiol Endocrinol Metab 2010 Jan;298(1):E49-58. Epub 2009 Nov 3 doi: 10.1152/ajpendo.00317.2009. PMID: 19887598Free PMC Article

Diagnosis

Paez HG, Ferrandi PJ, Pitzer CR, Mohamed JS, Alway SE
FASEB J 2023 Aug;37(8):e23050. doi: 10.1096/fj.202202029R. PMID: 37389860
Hipps D, Dobson PF, Warren C, McDonald D, Fuller A, Filby A, Bulmer D, Laude A, Russell O, Deehan DJ, Turnbull DM, Lawless C
Bone 2022 May;158:116371. Epub 2022 Feb 19 doi: 10.1016/j.bone.2022.116371. PMID: 35192969
Moss T, May M, Flanagan-Steet H, Caylor R, Jiang YH, McDonald M, Friez M, McConkie-Rosell A, Steet R
Cold Spring Harb Mol Case Stud 2021 Jun;7(3) Epub 2021 Jun 11 doi: 10.1101/mcs.a006081. PMID: 34117073Free PMC Article
Szarek E, Ball ER, Imperiale A, Tsokos M, Faucz FR, Giubellino A, Moussallieh FM, Namer IJ, Abu-Asab MS, Pacak K, Taïeb D, Carney JA, Stratakis CA
Endocr Relat Cancer 2015 Jun;22(3):345-52. Epub 2015 Mar 25 doi: 10.1530/ERC-15-0069. PMID: 25808178Free PMC Article
Wollheim CB
Diabetologia 2000 Mar;43(3):265-77. doi: 10.1007/s001250050044. PMID: 10768087

Therapy

Carraway MS, Suliman HB, Jones WS, Chen CW, Babiker A, Piantadosi CA
Circ Res 2010 Jun 11;106(11):1722-30. Epub 2010 Apr 15 doi: 10.1161/CIRCRESAHA.109.214353. PMID: 20395592Free 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
Hipps D, Dobson PF, Warren C, McDonald D, Fuller A, Filby A, Bulmer D, Laude A, Russell O, Deehan DJ, Turnbull DM, Lawless C
Bone 2022 May;158:116371. Epub 2022 Feb 19 doi: 10.1016/j.bone.2022.116371. PMID: 35192969
Fam HK, Choi K, Fougner L, Lim CJ, Boerkoel CF
Sci Rep 2018 Mar 9;8(1):4304. doi: 10.1038/s41598-018-22547-8. PMID: 29523818Free PMC Article
Lee WJ, Ahn HM, Na Y, Wadhwa R, Hong J, Yun CO
Sci Rep 2017 Oct 11;7(1):12957. doi: 10.1038/s41598-017-13485-y. PMID: 29021584Free PMC Article
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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