MCID: MTC088
MIFTS: 28

Mitochondrial Dna Depletion Syndrome 13

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

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 13

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 13:

Name: Mitochondrial Dna Depletion Syndrome 13 54 12 71 29 14 69
Mitochondrial Dna Depletion Syndrome, Encephalomyopathic Form with Variable Craniofacial Anomalies 56
Mtdna Depletion Syndrome, Encephalomyopathic Form with Variable Craniofacial Anomalies 56
Mtdps13 71

Characteristics:

Orphanet epidemiological data:

56
mitochondrial dna depletion syndrome, encephalomyopathic form with variable craniofacial anomalies
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
may result in early death
variable phenotype
onset at birth or early infancy


HPO:

32
mitochondrial dna depletion syndrome 13:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Mitochondrial Dna Depletion Syndrome 13

OMIM : 54
Mitochondrial DNA depletion syndrome-13 is an autosomal recessive disorder characterized by early infantile onset of encephalopathy, hypotonia, lactic acidosis, and severe global developmental delay. Cells derived from patient tissues show defects in mitochondrial oxidative phosphorylation and decreased mtDNA content (summary by Bonnen et al., 2013 and Gai et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). (615471)

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 13, also known as mitochondrial dna depletion syndrome, encephalomyopathic form with variable craniofacial anomalies, is related to fbxl4-related encephalomyopathic mitochondrial dna depletion syndrome and fbxl4-related mitochondrial dna depletion syndrome, encephalomyopathic form, and has symptoms including failure to thrive, scoliosis and nystagmus. An important gene associated with Mitochondrial Dna Depletion Syndrome 13 is FBXL4 (F-Box And Leucine Rich Repeat Protein 4). Affiliated tissues include skeletal muscle and liver.

UniProtKB/Swiss-Prot : 71 Mitochondrial DNA depletion syndrome 13: An autosomal recessive disorder characterized by early infantile onset of encephalopathy, hypotonia, lactic acidosis, and severe global developmental delay. Cells derived from patient tissues show defects in mitochondrial oxidative phosphorylation and decreased mtDNA content.

Related Diseases for Mitochondrial Dna Depletion Syndrome 13

Diseases related to Mitochondrial Dna Depletion Syndrome 13 via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 fbxl4-related encephalomyopathic mitochondrial dna depletion syndrome 11.4
2 fbxl4-related mitochondrial dna depletion syndrome, encephalomyopathic form 11.2

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 13

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive
poor growth

Head And Neck- Ears:
malformed ears
protruding ears

Abdomen- Gastroin testinal:
dysphagia
gastroesophageal reflux disease

Genitourinary- External Genitalia Male:
hypospadias

Head And Neck- Head:
microcephaly (in some patients)
plagiocephaly (in some patients)

Laboratory- Abnormalities:
increased serum lactate
increased serum alanine
increased serum ammonia
mitochondrial respiratory chain defects (skeletal muscle, fibroblasts)
depletion of mtdna (skeletal muscle, fibroblasts)
more
Skeletal- Spine:
scoliosis (in some patients)

Immunology:
recurrent infections (in some patients)

Head And Neck- Nose:
saddle nose

Genitourinary- Kidneys:
renal tubular acidosis (in some patients)

Muscle Soft Tissue:
hypotonia
muscle atrophy

Head And Neck- Eyes:
thick eyebrows
downslanting palpebral fissures
epicanthal folds
nystagmus (in some patients)
cataracts (in some patients)

Neurologic- Central Nervous System:
thin corpus callosum
white matter abnormalities
cerebral atrophy
seizures
encephalopathy
more
Head And Neck- Mouth:
everted lower lip

Metabolic Features:
lactic acidosis

Growth- Weight:
low birth weight

Head And Neck- Face:
narrow face
elongated face
dysmorphic facial features, variable (in some patients)

Hematology:
neutropenia (in some patients)

Cardiovascular- Heart:
hypertrophic cardiomyopathy (uncommon)
arrhythmia (uncommon)

Skeletal- Feet:
small feet (in some patients)


Clinical features from OMIM:

615471

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 13:

32 (show all 42)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 scoliosis 32 occasional (7.5%) HP:0002650
3 nystagmus 32 occasional (7.5%) HP:0000639
4 dysphagia 32 HP:0002015
5 dystonia 32 occasional (7.5%) HP:0001332
6 ataxia 32 occasional (7.5%) HP:0001251
7 recurrent infections 32 occasional (7.5%) HP:0002719
8 neutropenia 32 occasional (7.5%) HP:0001875
9 choreoathetosis 32 occasional (7.5%) HP:0001266
10 cerebral atrophy 32 HP:0002059
11 seizures 32 HP:0001250
12 microcephaly 32 HP:0000252
13 hypospadias 32 HP:0000047
14 encephalopathy 32 HP:0001298
15 global developmental delay 32 HP:0001263
16 hypertrophic cardiomyopathy 32 occasional (7.5%) HP:0001639
17 lactic acidosis 32 HP:0003128
18 increased serum lactate 32 HP:0002151
19 gastroesophageal reflux 32 HP:0002020
20 hypoplasia of the corpus callosum 32 HP:0002079
21 cataract 32 occasional (7.5%) HP:0000518
22 cerebellar atrophy 32 occasional (7.5%) HP:0001272
23 renal tubular acidosis 32 occasional (7.5%) HP:0001947
24 delayed myelination 32 HP:0012448
25 arrhythmia 32 occasional (7.5%) HP:0011675
26 plagiocephaly 32 occasional (7.5%) HP:0001357
27 narrow face 32 HP:0000275
28 leukodystrophy 32 HP:0002415
29 downslanted palpebral fissures 32 HP:0000494
30 epicanthus 32 HP:0000286
31 muscular hypotonia 32 HP:0001252
32 small for gestational age 32 HP:0001518
33 growth delay 32 HP:0001510
34 elevated hepatic transaminases 32 occasional (7.5%) HP:0002910
35 everted lower lip vermilion 32 HP:0000232
36 mitochondrial respiratory chain defects 32 HP:0200125
37 thick eyebrow 32 HP:0000574
38 skeletal muscle atrophy 32 HP:0003202
39 short foot 32 occasional (7.5%) HP:0001773
40 concave nasal ridge 32 HP:0011120
41 protruding ear 32 HP:0000411
42 hyperalaninemia 32 HP:0003348

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 13:


seizures

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 13

Search Clinical Trials , NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 13

Genetic Tests for Mitochondrial Dna Depletion Syndrome 13

Genetic tests related to Mitochondrial Dna Depletion Syndrome 13:

id Genetic test Affiliating Genes
1 Mitochondrial Dna Depletion Syndrome 13 (encephalomyopathic Type) 29

Anatomical Context for Mitochondrial Dna Depletion Syndrome 13

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 13:

39
Skeletal Muscle, Liver

Publications for Mitochondrial Dna Depletion Syndrome 13

Articles related to Mitochondrial Dna Depletion Syndrome 13:

id Title Authors Year
1
A novel mutation in FBXL4 in a Norwegian child with encephalomyopathic mitochondrial DNA depletion syndrome 13. ( 27182039 )
2016

Variations for Mitochondrial Dna Depletion Syndrome 13

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 13:

71
id Symbol AA change Variation ID SNP ID
1 FBXL4 p.Ile205Thr VAR_070858
2 FBXL4 p.Arg482Trp VAR_070859 rs398123061
3 FBXL4 p.Ile551Asn VAR_070860
4 FBXL4 p.Asp565Gly VAR_070861 rs398123062
5 FBXL4 p.Gly568Ala VAR_070862 rs398123060
6 FBXL4 p.Gln597Pro VAR_070863 rs201989042
7 FBXL4 p.Leu481Pro VAR_076547 rs772037717

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 13:

6 (show top 50) (show all 53)
id Gene Variation Type Significance SNP ID Assembly Location
1 FBXL4 NM_012160.4(FBXL4): c.1555C> T (p.Gln519Ter) single nucleotide variant Pathogenic rs398123059 GRCh37 Chromosome 6, 99323438: 99323438
2 FBXL4 NM_012160.4(FBXL4): c.1303C> T (p.Arg435Ter) single nucleotide variant Pathogenic rs201889294 GRCh37 Chromosome 6, 99347158: 99347158
3 FBXL4 NM_012160.4(FBXL4): c.1703G> C (p.Gly568Ala) single nucleotide variant Pathogenic/Likely pathogenic rs398123060 GRCh37 Chromosome 6, 99322317: 99322317
4 FBXL4 NM_012160.4(FBXL4): c.1444C> T (p.Arg482Trp) single nucleotide variant Pathogenic/Likely pathogenic rs398123061 GRCh37 Chromosome 6, 99323549: 99323549
5 FBXL4 NM_012160.4(FBXL4): c.1694A> G (p.Asp565Gly) single nucleotide variant Pathogenic/Likely pathogenic rs398123062 GRCh37 Chromosome 6, 99323299: 99323299
6 FBXL4 NM_012160.4(FBXL4): c.64C> T (p.Arg22Ter) single nucleotide variant Pathogenic rs200440128 GRCh37 Chromosome 6, 99374801: 99374801
7 FBXL4 NM_012160.4(FBXL4): c.1442T> C (p.Leu481Pro) single nucleotide variant Likely pathogenic rs772037717 GRCh38 Chromosome 6, 98875675: 98875675
8 FBXL4 NM_001278716.1(FBXL4): c.1546_1563del18 (p.Pro516_Ser521del) deletion Likely pathogenic rs878853112 GRCh37 Chromosome 6, 99323430: 99323447
9 FBXL4 NM_012160.4(FBXL4): c.1641_1642delTG (p.Cys547Terfs) deletion Pathogenic rs765882664 GRCh37 Chromosome 6, 99323351: 99323352
10 FBXL4 NM_012160.4(FBXL4): c.618_621dupACTG (p.Glu208Thrfs) duplication Pathogenic rs886041625 GRCh37 Chromosome 6, 99365487: 99365490
11 FBXL4 NM_012160.4(FBXL4): c.419T> C (p.Val140Ala) single nucleotide variant Pathogenic/Likely pathogenic rs1057519447 GRCh37 Chromosome 6, 99374446: 99374446
12 FBXL4 NM_012160.4(FBXL4): c.1304G> A (p.Arg435Gln) single nucleotide variant Likely pathogenic rs754142863 GRCh37 Chromosome 6, 99347157: 99347157
13 FBXL4 NM_012160.4(FBXL4): c.1838T> A (p.Val613Glu) single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 99322182: 99322182
14 FBXL4 NM_001278716.1(FBXL4): c.1836delA (p.Val613Cysfs) deletion Likely pathogenic rs751656896 GRCh37 Chromosome 6, 99322184: 99322184
15 FBXL4 NM_012160.4(FBXL4): c.1790A> C (p.Gln597Pro) single nucleotide variant Likely pathogenic rs201989042 GRCh38 Chromosome 6, 98874354: 98874354
16 FBXL4 NM_012160.4(FBXL4): c.1772A> G (p.Asp591Gly) single nucleotide variant Likely pathogenic rs747618415 GRCh38 Chromosome 6, 98874372: 98874372
17 FBXL4 NM_012160.4(FBXL4): c.1750T> C (p.Cys584Arg) single nucleotide variant Likely pathogenic GRCh38 Chromosome 6, 98874394: 98874394
18 FBXL4 NM_012160.4(FBXL4): c.1698A> G (p.Ile566Met) single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 99323295: 99323295
19 FBXL4 NM_012160.4(FBXL4): c.1687C> T (p.Gln563Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 6, 99323306: 99323306
20 FBXL4 NM_012160.4(FBXL4): c.1652T> A (p.Ile551Asn) single nucleotide variant Pathogenic GRCh38 Chromosome 6, 98875465: 98875465
21 FBXL4 NM_001278716.1(FBXL4): c.1648_1649delGA (p.Asp550Hisfs) deletion Pathogenic GRCh38 Chromosome 6, 98875468: 98875469
22 FBXL4 NM_012160.4(FBXL4): c.1622C> T (p.Thr541Ile) single nucleotide variant Likely pathogenic GRCh38 Chromosome 6, 98875495: 98875495
23 FBXL4 NM_012160.4(FBXL4): c.1586C> A (p.Ala529Glu) single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 99323407: 99323407
24 FBXL4 NM_012160.4(FBXL4): c.1540T> G (p.Trp514Gly) single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 99323453: 99323453
25 FBXL4 NM_012160.4(FBXL4): c.1411G> A (p.Ala471Thr) single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 99323582: 99323582
26 FBXL4 NM_012160.4(FBXL4): c.1389+3_1389+6del deletion Pathogenic GRCh37 Chromosome 6, 99328423: 99328426
27 FBXL4 NM_012160.4(FBXL4): c.1360C> T (p.Gln454Ter) single nucleotide variant Likely pathogenic rs750973870 GRCh37 Chromosome 6, 99328458: 99328458
28 FBXL4 NM_012160.4(FBXL4): c.1317G> A (p.Glu439=) single nucleotide variant Pathogenic GRCh37 Chromosome 6, 99347144: 99347144
29 FBXL4 NM_012160.4(FBXL4): c.1304G> T (p.Arg435Leu) single nucleotide variant Likely pathogenic rs754142863 GRCh37 Chromosome 6, 99347157: 99347157
30 FBXL4 NM_012160.4(FBXL4): c.1288C> T (p.Arg430Ter) single nucleotide variant Likely pathogenic rs758395213 GRCh37 Chromosome 6, 99347173: 99347173
31 FBXL4 NM_012160.4(FBXL4): c.1232G> A (p.Cys411Tyr) single nucleotide variant Likely pathogenic rs773850151 GRCh37 Chromosome 6, 99347229: 99347229
32 FBXL4 NM_012160.4(FBXL4): c.1229C> T (p.Ser410Phe) single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 99347232: 99347232
33 FBXL4 NM_012160.4(FBXL4): c.1210C> T (p.Gln404Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 6, 98899375: 98899375
34 FBXL4 NM_001278716.1(FBXL4): c.1067delG (p.Gly356Alafs) deletion Pathogenic GRCh38 Chromosome 6, 98905462: 98905462
35 FBXL4 NM_012160.4(FBXL4): c.903T> A (p.Cys301Ter) single nucleotide variant Likely pathogenic rs775768793 GRCh38 Chromosome 6, 98905626: 98905626
36 FBXL4 NM_012160.4(FBXL4): c.859-1G> T single nucleotide variant Pathogenic rs368965675 GRCh38 Chromosome 6, 98905671: 98905671
37 FBXL4 NM_012160.4(FBXL4): c.858+5G> C single nucleotide variant Likely pathogenic GRCh38 Chromosome 6, 98917369: 98917369
38 FBXL4 NM_012160.4(FBXL4): c.858+1G> T single nucleotide variant Pathogenic GRCh38 Chromosome 6, 98917373: 98917373
39 FBXL4 NM_012160.4(FBXL4): c.662A> T (p.Asp221Val) single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 99365446: 99365446
40 FBXL4 NM_012160.4(FBXL4): c.661G> C (p.Asp221His) single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 99365447: 99365447
41 FBXL4 NM_012160.4(FBXL4): c.616C> T (p.Arg206Ter) single nucleotide variant Pathogenic rs964532159 GRCh38 Chromosome 6, 98917616: 98917616
42 FBXL4 NM_012160.4(FBXL4): c.614T> C (p.Ile205Thr) single nucleotide variant Likely pathogenic GRCh38 Chromosome 6, 98917618: 98917618
43 FBXL4 NM_012160.4(FBXL4): c.513-1G> A single nucleotide variant Pathogenic GRCh37 Chromosome 6, 99365596: 99365596
44 FBXL4 NM_012160.4(FBXL4): c.445G> A (p.Gly149Arg) single nucleotide variant Likely pathogenic GRCh37 Chromosome 6, 99374420: 99374420
45 FBXL4 NM_012160.4(FBXL4): c.417_418insA (p.Val140Serfs) insertion Likely pathogenic rs761902417 GRCh37 Chromosome 6, 99374447: 99374448
46 FBXL4 NM_012160.4(FBXL4): c.415_416insTT (p.Ala139Valfs) insertion Likely pathogenic rs767543583 GRCh37 Chromosome 6, 99374449: 99374450
47 FBXL4 NM_012160.4(FBXL4): c.370C> T (p.Gln124Ter) single nucleotide variant Likely pathogenic rs761974928 GRCh37 Chromosome 6, 99374495: 99374495
48 FBXL4 NM_001278716.1(FBXL4): c.326delG (p.Ser109Metfs) deletion Pathogenic rs761215749 GRCh37 Chromosome 6, 99374539: 99374539
49 FBXL4 NM_012160.4(FBXL4): c.316C> T (p.Gln106Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 6, 99374549: 99374549
50 FBXL4 NM_012160.4(FBXL4): c.292C> T (p.Arg98Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 6, 99374573: 99374573

Expression for Mitochondrial Dna Depletion Syndrome 13

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 13.

Pathways for Mitochondrial Dna Depletion Syndrome 13

GO Terms for Mitochondrial Dna Depletion Syndrome 13

Sources for Mitochondrial Dna Depletion Syndrome 13

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