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Mitochondrial complex 1 deficiency, nuclear type 18(MC1DN18)

MedGen UID:
1648321
Concept ID:
C4748790
Disease or Syndrome
Synonym: MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 18
 
Gene (location): NDUFAF3 (3p21.31)
 
Monarch Initiative: MONDO:0032623
OMIM®: 618240

Definition

Mitochondrial complex I deficiency nuclear type 18 (MC1DN18) is an autosomal recessive disorder of the oxidative phosphorylation (OXPHOS) system. Affected individuals present with lactic acidemia soon after birth. Clinical features may include hypertonia or hypotonia, poor feeding, respiratory problems, leukomalacia, and seizures. Death occurs by 6 months of age (Saada et al., 2009). For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. [from OMIM]

Clinical features

From HPO
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Hydroureter
MedGen UID:
101073
Concept ID:
C0521620
Anatomical Abnormality
The distention of the ureter with urine.
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.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
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.
Increased CSF lactate
MedGen UID:
257904
Concept ID:
C1167918
Finding
Increased concentration of lactate in the cerebrospinal fluid.
Reduced eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
A reduced frequency or duration of eye contact.
Myoclonic seizure
MedGen UID:
1385980
Concept ID:
C4317123
Sign or Symptom
A myoclonic seizure is a type of motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
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.
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.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
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

Prognosis

Thompson K, Mai N, Oláhová M, Scialó F, Formosa LE, Stroud DA, Garrett M, Lax NZ, Robertson FM, Jou C, Nascimento A, Ortez C, Jimenez-Mallebrera C, Hardy SA, He L, Brown GK, Marttinen P, McFarland R, Sanz A, Battersby BJ, Bonnen PE, Ryan MT, Chrzanowska-Lightowlers ZM, Lightowlers RN, Taylor RW
EMBO Mol Med 2018 Nov;10(11) doi: 10.15252/emmm.201809060. PMID: 30201738Free PMC Article

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