MCID: ENC051
MIFTS: 26

Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1

Categories: Genetic diseases, Neuronal diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Encephalopathy, Lethal, Due to Defective Mitochondrial...

MalaCards integrated aliases for Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1:

Name: Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1 54
Encephalopahty, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 71 13
Encephalopathy Due to Defective Mitochondrial and Peroxisomal Fission 1 71 29
Encephalopathy, Lethal, Due to Defective Mitochondrial and Peroxisomal Fission 69
Encephalopahty, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1 71
Lethal Encephalopathy Due to Mitochondrial and Peroxisomal Fission Defect 56
Empf1 71
Empf 71

Characteristics:

Orphanet epidemiological data:

56
lethal encephalopathy due to mitochondrial and peroxisomal fission defect
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal dominant
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
variable features
onset in first days of life
some patients may have onset in mid-childhood
some patients may not have biochemical evidence of mitochondrial or peroxisomal dysfunction on standard screening


HPO:

32
encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1:
Mortality/Aging death in infancy
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Encephalopathy, Lethal, Due to Defective Mitochondrial...

UniProtKB/Swiss-Prot : 71 Encephalopathy due to defective mitochondrial and peroxisomal fission 1: A rare autosomal dominant systemic disorder resulting in lack of neurologic development and death in infancy. After birth, infants present in the first week of life with poor feeding and neurologic impairment, including hypotonia, little spontaneous movement, no tendon reflexes, no response to light stimulation, and poor visual fixation. Other features include mildly elevated plasma concentration of very-long-chain fatty acids, lactic acidosis, microcephaly, deep- set eyes, optic atrophy and hypoplasia, and an abnormal gyral pattern in both frontal lobes associated with dysmyelination.

MalaCards based summary : Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1, also known as encephalopahty, lethal, due to defective mitochondrial peroxisomal fission, is related to encephalopathy due to defective mitochondrial and peroxisomal fission 2 and pulmonary fibrosis, and has symptoms including failure to thrive, optic atrophy and horizontal nystagmus. An important gene associated with Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1 is DNM1L (Dynamin 1 Like). Affiliated tissues include eye and skeletal muscle.

OMIM : 54
Encephalopathy due to defective mitochondrial and peroxisomal fission-1 is characterized by delayed psychomotor development and hypotonia that may lead to death in childhood. Many patients develop refractory seizures, consistent with an epileptic encephalopathy, and thereafter show neurologic decline. The age at onset, features, and severity are variable, and some patients may not have clinical evidence of mitochondrial or peroxisomal dysfunction (summary by Sheffer et al., 2016; Fahrner et al., 2016). (614388)

Related Diseases for Encephalopathy, Lethal, Due to Defective Mitochondrial...

Diseases in the Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1 family:

Lethal Encephalopathy Due to Defective Mitochondrial Peroxisomal Fission

Diseases related to Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1 via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 encephalopathy due to defective mitochondrial and peroxisomal fission 2 10.9
2 pulmonary fibrosis 9.9

Symptoms & Phenotypes for Encephalopathy, Lethal, Due to Defective Mitochondrial...

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive
poor feeding

Muscle Soft Tissue:
hypotonia
skeletal muscle biopsy shows elongated mitochondria
abnormal mitochondrial concentric cristae
increased dense granules in mitochondria
subsarcolemmal mitochondrial aggregates
more
Head And Neck- Head:
microcephaly

Prenatal Manifestations- Movement:
decreased fetal movement

Metabolic Features:
lactic acidosis (in some patients)

Neurologic- Central Nervous System:
hypotonia
delayed psychomotor development
seizures (in some patients)
cerebral atrophy
pyramidal signs
more
Head And Neck- Eyes:
nystagmus
strabismus
oculomotor apraxia
optic atrophy (patient a)
poor visual fixation
more
Neurologic- Peripheral Nervous System:
areflexia

Laboratory- Abnormalities:
defect in mitochondrial fission
defect in peroxisomal fission
increased serum and csf lactate (in some patients)
fibroblasts show decreased peroxisomes arranged in rows
fibroblasts show elongated, tangled, tubular mitochondria

Head And Neck- Face:
pointed chin (patient a)


Clinical features from OMIM:

614388

Human phenotypes related to Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1:

32 (show all 12)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 optic atrophy 32 HP:0000648
3 horizontal nystagmus 32 HP:0000666
4 microcephaly 32 HP:0000252
5 encephalopathy 32 HP:0001298
6 lactic acidosis 32 HP:0003128
7 areflexia 32 HP:0001284
8 pointed chin 32 HP:0000307
9 feeding difficulties 32 HP:0011968
10 decreased fetal movement 32 HP:0001558
11 muscular hypotonia 32 HP:0001252
12 deeply set eye 32 HP:0000490

UMLS symptoms related to Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1:


abnormal pyramidal signs

Drugs & Therapeutics for Encephalopathy, Lethal, Due to Defective Mitochondrial...

Search Clinical Trials , NIH Clinical Center for Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1

Genetic Tests for Encephalopathy, Lethal, Due to Defective Mitochondrial...

Genetic tests related to Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1:

id Genetic test Affiliating Genes
1 Encephalopathy Due to Defective Mitochondrial and Peroxisomal Fission 1 29

Anatomical Context for Encephalopathy, Lethal, Due to Defective Mitochondrial...

MalaCards organs/tissues related to Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1:

39
Eye, Skeletal Muscle

Publications for Encephalopathy, Lethal, Due to Defective Mitochondrial...

Variations for Encephalopathy, Lethal, Due to Defective Mitochondrial...

UniProtKB/Swiss-Prot genetic disease variations for Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1:

71
id Symbol AA change Variation ID SNP ID
1 DNM1L p.Ala395Asp VAR_063704 rs121908531
2 DNM1L p.Gly362Ser VAR_076317
3 DNM1L p.Arg403Cys VAR_076318 rs863223953

ClinVar genetic disease variations for Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 DNM1L NM_012062.4(DNM1L): c.1184C> A (p.Ala395Asp) single nucleotide variant Pathogenic rs121908531 GRCh37 Chromosome 12, 32884052: 32884052
2 DNM1L NM_012062.4(DNM1L): c.1207C> T (p.Arg403Cys) single nucleotide variant Pathogenic rs863223953 GRCh38 Chromosome 12, 32731362: 32731362
3 DNM1L NM_005690.4(DNM1L): c.1337G> T (p.Cys446Phe) single nucleotide variant Likely pathogenic rs879253874 GRCh37 Chromosome 12, 32884426: 32884426
4 DNM1L NM_012062.4(DNM1L): c.1085G> A (p.Gly362Asp) single nucleotide variant Pathogenic rs879255685 GRCh37 Chromosome 12, 32883953: 32883953
5 DNM1L NM_012062.4(DNM1L): c.1084G> A (p.Gly362Ser) single nucleotide variant Pathogenic rs886037861 GRCh37 Chromosome 12, 32883952: 32883952
6 DNM1L NM_001278464.1(DNM1L): c.261dupA (p.Trp88Metfs) duplication Pathogenic rs879255686 GRCh37 Chromosome 12, 32858769: 32858769
7 DNM1L NM_012062.4(DNM1L): c.346_347delGA (p.Glu116Lysfs) deletion Pathogenic rs879255687 GRCh38 Chromosome 12, 32708201: 32708202
8 DNM1L NM_012062.4(DNM1L): c.106A> G (p.Ser36Gly) single nucleotide variant Pathogenic rs879255688 GRCh37 Chromosome 12, 32854352: 32854352
9 DNM1L NM_012062.4(DNM1L): c.1048G> A (p.Gly350Arg) single nucleotide variant Pathogenic rs879255689 GRCh37 Chromosome 12, 32875536: 32875536
10 DNM1L NM_012063.3(DNM1L): c.1135G> A (p.Glu379Lys) single nucleotide variant Likely pathogenic rs1057518694 GRCh37 Chromosome 12, 32884003: 32884003

Expression for Encephalopathy, Lethal, Due to Defective Mitochondrial...

Search GEO for disease gene expression data for Encephalopathy, Lethal, Due to Defective Mitochondrial Peroxisomal Fission 1.

Pathways for Encephalopathy, Lethal, Due to Defective Mitochondrial...

GO Terms for Encephalopathy, Lethal, Due to Defective Mitochondrial...

Sources for Encephalopathy, Lethal, Due to Defective Mitochondrial...

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