HLD5
MCID: LKD009
MIFTS: 38

Leukodystrophy, Hypomyelinating, 5 (HLD5)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 5

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 5:

Name: Leukodystrophy, Hypomyelinating, 5 58 54 76 13
Hypomyelination and Congenital Cataract 25 54 26 30 6 41 74
Hld5 58 12 54 76
Hypomyelination-Congenital Cataract Syndrome 12 60
Hypomyelinating Leukodystrophy 5 12 15
Hcc 26 76
Hypomyelination and Congenital Cataract: Hcc 58
Hypomyelination with Congenital Cataract 76
Hypomyelination - Congenital Cataract 54

Characteristics:

Orphanet epidemiological data:

60
hypomyelination-congenital cataract syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
variable severity


HPO:

33
leukodystrophy, hypomyelinating, 5:
Onset and clinical course variable expressivity infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leukodystrophy, Hypomyelinating, 5

NIH Rare Diseases : 54 Hypomyelination and congenitalcataract is a very rare disease characterized by cloudy coverings of the eye that are present at birth (congenital cataracts) and neurologic impairment that becomes apparent after the first year of life. The neurologic impairment is progressive and presents as ataxia and spasticity. Affected individuals may lose the ability to walk. Signs and symptoms may vary but can include loss of sensation in the hands and feet (peripheral neuropathy), curvature of the spine (scoliosis), difficulty speaking (dysarthria), seizures, and moderate intellectual disability. Hypomyelination and congenital cataract is caused by a change (mutation ) in the FAM126A gene and is inherited in an autosomal recessive manner. Diagnosis of hypomyelination and congenital cataract is based on clinical findings of muscle weakness and cataracts, and a brain MRI that indicates a loss of the myelin surrounding the neurons. The diagnosis can be confirmed by genetic testing of the FAM126A gene. Treatment is focused on relieving symptoms of the condition and may include physical therapy, special education, and medication to treat seizures.

MalaCards based summary : Leukodystrophy, Hypomyelinating, 5, also known as hypomyelination and congenital cataract, is related to leukodystrophy and hepatocellular carcinoma, and has symptoms including abnormal pyramidal signs, action tremor and cerebellar signs. An important gene associated with Leukodystrophy, Hypomyelinating, 5 is FAM126A (Family With Sequence Similarity 126 Member A). Affiliated tissues include eye, brain and testes, and related phenotypes are global developmental delay and intellectual disability, moderate

Disease Ontology : 12 A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of congenital cataract, progressive neurologic impairment, and diffuse myelin deficiency that has material basis in homozygous mutation in the FAM126A gene on chromosome 7p15.

Genetics Home Reference : 26 Hypomyelination and congenital cataract is an inherited condition that affects the nervous system and the eyes. This disease is one of a group of genetic disorders called leukoencephalopathies. Leukoencephalopathies involve abnormalities of the brain's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. Hypomyelination and congenital cataract is caused by a reduced ability to form myelin (hypomyelination). Additionally, people with this disorder are typically born with a clouding of the lens (cataract) in both eyes.

UniProtKB/Swiss-Prot : 76 Leukodystrophy, hypomyelinating, 5: A hypomyelinating leukodystrophy associated with congenital cataract. It is clinically characterized by congenital cataract, progressive neurologic impairment, and diffuse myelin deficiency. Affected individuals experience progressive pyramidal and cerebellar dysfunction, muscle weakness and wasting prevailingly in the lower limbs. Mental deficiency ranges from mild to moderate. HLD5 shows clinical variability, but features of hypomyelination combined with increased periventricular white matter water content are consistently observed.

Description from OMIM: 610532
GeneReviews: NBK2587

Related Diseases for Leukodystrophy, Hypomyelinating, 5

Diseases in the Hypomyelinating Leukodystrophy family:

Leukodystrophy, Hypomyelinating, 3 Leukodystrophy, Hypomyelinating, 2
Leukodystrophy, Hypomyelinating, 5 Leukodystrophy, Hypomyelinating, 4
Leukodystrophy, Hypomyelinating, 6 Leukodystrophy, Hypomyelinating, 9
Leukodystrophy, Hypomyelinating, 10 Leukodystrophy, Hypomyelinating, 11
Leukodystrophy, Hypomyelinating, 12 Leukodystrophy, Hypomyelinating, 13
Leukodystrophy, Hypomyelinating, 14 Leukodystrophy, Hypomyelinating, 15
Leukodystrophy, Hypomyelinating, 16 Leukodystrophy, Hypomyelinating, 17

Diseases related to Leukodystrophy, Hypomyelinating, 5 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 78)
# Related Disease Score Top Affiliating Genes
1 leukodystrophy 28.7 FAM126A PLP1 TUBB4A
2 hepatocellular carcinoma 12.2
3 childhood hepatocellular carcinoma 11.9
4 fibrolamellar carcinoma 11.7
5 linear skin defects with multiple congenital anomalies 1 11.2
6 thyroid carcinoma, hurthle cell 11.2
7 cardiomyopathy, infantile histiocytoid 11.1
8 adult hepatocellular carcinoma 11.1
9 combined hepatocellular carcinoma and cholangiocarcinoma 11.1
10 benign childhood occipital epilepsy, panayiotopoulos type 10.7
11 hepatitis 10.7
12 liver cirrhosis 10.6
13 hepatitis c 10.5
14 liver disease 10.5
15 hepatitis c virus 10.4
16 hepatitis b 10.4
17 fatty liver disease 10.3
18 nonalcoholic fatty liver disease 10.3
19 viral hepatitis 10.2
20 cholangiocarcinoma 10.2
21 thrombosis 10.2
22 hypoxia 10.2
23 microphthalmia 10.0
24 tetanus 10.0
25 portal vein thrombosis 10.0
26 intrahepatic cholangiocarcinoma 10.0
27 multiple sclerosis 10.0
28 tetralogy of fallot 10.0
29 autoimmune hepatitis 10.0
30 adenocarcinoma 10.0
31 vaccinia 10.0
32 adenoma 10.0
33 nonalcoholic steatohepatitis 10.0
34 rapidly involuting congenital hemangioma 10.0
35 breast cancer 9.8
36 diaphragmatic hernia, congenital 9.8
37 ovarian cancer 9.8
38 retinoblastoma 9.8
39 pancreatic cancer 9.8
40 polycythemia vera 9.8
41 body mass index quantitative trait locus 11 9.8
42 immunodysregulation, polyendocrinopathy, and enteropathy, x-linked 9.8
43 horns in sheep 9.8
44 polydactyly 9.8
45 body mass index quantitative trait locus 1 9.8
46 gastrointestinal stromal tumor 9.8
47 body mass index quantitative trait locus 10 9.8
48 body mass index quantitative trait locus 14 9.8
49 fatty liver disease, nonalcoholic 1 9.8
50 body mass index quantitative trait locus 18 9.8

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 5:



Diseases related to Leukodystrophy, Hypomyelinating, 5

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 5

Human phenotypes related to Leukodystrophy, Hypomyelinating, 5:

60 33 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 60 33 hallmark (90%) Very frequent (99-80%) HP:0001263
2 intellectual disability, moderate 60 33 hallmark (90%) Very frequent (99-80%) HP:0002342
3 cerebral hypomyelination 60 33 hallmark (90%) Very frequent (99-80%) HP:0006808
4 abnormal pyramidal sign 33 hallmark (90%) HP:0007256
5 developmental cataract 33 hallmark (90%) HP:0000519
6 abnormal cerebellum morphology 33 hallmark (90%) HP:0001317
7 intellectual disability 33 HP:0001249
8 seizures 33 HP:0001250
9 dysarthria 33 HP:0001260
10 hyperreflexia 33 HP:0001347
11 scoliosis 33 HP:0002650
12 abnormal pyramidal signs 60 Very frequent (99-80%)
13 babinski sign 33 HP:0003487
14 intention tremor 33 HP:0002080
15 decreased motor nerve conduction velocity 33 HP:0003431
16 motor delay 33 HP:0001270
17 abnormality of the cerebellum 60 Very frequent (99-80%)
18 lower limb muscle weakness 33 HP:0007340
19 polyneuropathy 33 HP:0001271
20 leukodystrophy 33 HP:0002415
21 lower limb amyotrophy 33 HP:0007210
22 muscular hypotonia of the trunk 33 HP:0008936
23 congenital cataract 60 Very frequent (99-80%)
24 loss of ability to walk 33 HP:0006957
25 onion bulb formation 33 HP:0003383
26 cerebral white matter atrophy 33 HP:0012762
27 truncal titubation 33 HP:0030147

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
dysarthria
hyperreflexia
intention tremor
truncal titubation
delayed motor development
more
Skeletal Spine:
scoliosis, progressive

Muscle Soft Tissue:
weakness and wasting of the lower limbs

Neurologic Peripheral Nervous System:
peripheral neuropathy
decreased motor nerve conduction velocities
sural nerve biopsy shows decrease in myelinated fibers
loss of myelin
abnormal folding of the myelin sheath
more
Head And Neck Eyes:
cataracts, usually congenital

Clinical features from OMIM:

610532

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 5:


abnormal pyramidal signs, action tremor, cerebellar signs

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 5

Search Clinical Trials , NIH Clinical Center for Leukodystrophy, Hypomyelinating, 5

Genetic Tests for Leukodystrophy, Hypomyelinating, 5

Genetic tests related to Leukodystrophy, Hypomyelinating, 5:

# Genetic test Affiliating Genes
1 Hypomyelination and Congenital Cataract 30 FAM126A

Anatomical Context for Leukodystrophy, Hypomyelinating, 5

MalaCards organs/tissues related to Leukodystrophy, Hypomyelinating, 5:

42
Eye, Brain, Testes, Cerebellum

Publications for Leukodystrophy, Hypomyelinating, 5

Articles related to Leukodystrophy, Hypomyelinating, 5:

# Title Authors Year
1
Novel FAM126A mutations in hypomyelination and congenital cataract disease. ( 23998934 )
2013
2
Hypomyelination and congenital cataract: identification of novel mutations in two unrelated families. ( 22749724 )
2013
3
Hyccin, the molecule mutated in the leukodystrophy hypomyelination and congenital cataract (HCC), is a neuronal protein. ( 22461884 )
2012
4
Hypomyelination and congenital cataract: broadening the clinical phenotype. ( 21911699 )
2011
5
Hypomyelination and congenital cataract: neuroimaging features of a novel inherited white matter disorder. ( 17974614 )
2008
6
Phenotypic characterization of hypomyelination and congenital cataract. ( 17683097 )
2007
7
Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract. ( 16951682 )
2006
8
Hypomyelination and Congenital Cataract ( 20301737 )
1993

Variations for Leukodystrophy, Hypomyelinating, 5

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 5:

76
# Symbol AA change Variation ID SNP ID
1 FAM126A p.Leu53Pro VAR_030647 rs72549407
2 FAM126A p.Cys57Arg VAR_075100

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 5:

6 (show top 50) (show all 183)
# Gene Variation Type Significance SNP ID Assembly Location
1 FAM126A NM_032581.3(FAM126A): c.51+1G> A single nucleotide variant Pathogenic rs72549405 GRCh37 Chromosome 7, 23030679: 23030679
2 FAM126A NM_032581.3(FAM126A): c.51+1G> A single nucleotide variant Pathogenic rs72549405 GRCh38 Chromosome 7, 22991060: 22991060
3 FAM126A NM_032581.3(FAM126A): c.414+1G> T single nucleotide variant Pathogenic rs72549406 GRCh37 Chromosome 7, 23016959: 23016959
4 FAM126A NM_032581.3(FAM126A): c.414+1G> T single nucleotide variant Pathogenic rs72549406 GRCh38 Chromosome 7, 22977340: 22977340
5 FAM126A NM_032581.3(FAM126A): c.158T> C (p.Leu53Pro) single nucleotide variant Pathogenic rs72549407 GRCh37 Chromosome 7, 23018063: 23018063
6 FAM126A NM_032581.3(FAM126A): c.158T> C (p.Leu53Pro) single nucleotide variant Pathogenic rs72549407 GRCh38 Chromosome 7, 22978444: 22978444
7 FAM126A FAM126A, 4-KB DEL deletion Pathogenic
8 FAM126A FAM126A: c.627-439_831+348del deletion Pathogenic GRCh37 Chromosome 7, 23000506: 23004589
9 FAM126A FAM126A: c.627-439_831+348del deletion Pathogenic GRCh38 Chromosome 7, 22960887: 22964970
10 FAM126A NM_032581.3(FAM126A): c.624A> G (p.Ser208=) single nucleotide variant Benign rs3735231 GRCh37 Chromosome 7, 23015831: 23015831
11 FAM126A NM_032581.3(FAM126A): c.624A> G (p.Ser208=) single nucleotide variant Benign rs3735231 GRCh38 Chromosome 7, 22976212: 22976212
12 FAM126A NM_032581.3(FAM126A): c.414+1G> C single nucleotide variant not provided rs72549406 GRCh37 Chromosome 7, 23016959: 23016959
13 FAM126A NM_032581.3(FAM126A): c.414+1G> C single nucleotide variant not provided rs72549406 GRCh38 Chromosome 7, 22977340: 22977340
14 FAM126A NM_032581.3(FAM126A): c.*4278_*4279insGT insertion Benign rs35708583 GRCh38 Chromosome 7, 22941310: 22941311
15 FAM126A NM_032581.3(FAM126A): c.*4278_*4279insGT insertion Benign rs35708583 GRCh37 Chromosome 7, 22980929: 22980930
16 FAM126A NM_032581.3(FAM126A): c.*4221G> C single nucleotide variant Uncertain significance rs539079827 GRCh38 Chromosome 7, 22941368: 22941368
17 FAM126A NM_032581.3(FAM126A): c.*4221G> C single nucleotide variant Uncertain significance rs539079827 GRCh37 Chromosome 7, 22980987: 22980987
18 FAM126A NM_032581.3(FAM126A): c.*3753C> T single nucleotide variant Uncertain significance rs186672766 GRCh38 Chromosome 7, 22941836: 22941836
19 FAM126A NM_032581.3(FAM126A): c.*3753C> T single nucleotide variant Uncertain significance rs186672766 GRCh37 Chromosome 7, 22981455: 22981455
20 FAM126A NM_032581.3(FAM126A): c.*3001A> G single nucleotide variant Benign rs2286495 GRCh38 Chromosome 7, 22942588: 22942588
21 FAM126A NM_032581.3(FAM126A): c.*3001A> G single nucleotide variant Benign rs2286495 GRCh37 Chromosome 7, 22982207: 22982207
22 FAM126A NM_032581.3(FAM126A): c.*2976G> T single nucleotide variant Likely benign rs17725943 GRCh38 Chromosome 7, 22942613: 22942613
23 FAM126A NM_032581.3(FAM126A): c.*2976G> T single nucleotide variant Likely benign rs17725943 GRCh37 Chromosome 7, 22982232: 22982232
24 FAM126A NM_032581.3(FAM126A): c.*2905T> C single nucleotide variant Uncertain significance rs546858657 GRCh38 Chromosome 7, 22942684: 22942684
25 FAM126A NM_032581.3(FAM126A): c.*2905T> C single nucleotide variant Uncertain significance rs546858657 GRCh37 Chromosome 7, 22982303: 22982303
26 FAM126A NM_032581.3(FAM126A): c.*2108G> A single nucleotide variant Uncertain significance rs549000863 GRCh38 Chromosome 7, 22943481: 22943481
27 FAM126A NM_032581.3(FAM126A): c.*2108G> A single nucleotide variant Uncertain significance rs549000863 GRCh37 Chromosome 7, 22983100: 22983100
28 FAM126A NM_032581.3(FAM126A): c.*1506T> A single nucleotide variant Benign rs4607514 GRCh37 Chromosome 7, 22983702: 22983702
29 FAM126A NM_032581.3(FAM126A): c.*1506T> A single nucleotide variant Benign rs4607514 GRCh38 Chromosome 7, 22944083: 22944083
30 FAM126A NM_032581.3(FAM126A): c.*515A> T single nucleotide variant Uncertain significance rs549927461 GRCh37 Chromosome 7, 22984693: 22984693
31 FAM126A NM_032581.3(FAM126A): c.*515A> T single nucleotide variant Uncertain significance rs549927461 GRCh38 Chromosome 7, 22945074: 22945074
32 FAM126A NM_032581.3(FAM126A): c.*435_*436delCTinsTG indel Uncertain significance rs71527512 GRCh38 Chromosome 7, 22945153: 22945154
33 FAM126A NM_032581.3(FAM126A): c.*435_*436delCTinsTG indel Uncertain significance rs71527512 GRCh37 Chromosome 7, 22984772: 22984773
34 FAM126A NM_032581.3(FAM126A): c.*384A> G single nucleotide variant Benign rs2286494 GRCh38 Chromosome 7, 22945205: 22945205
35 FAM126A NM_032581.3(FAM126A): c.*384A> G single nucleotide variant Benign rs2286494 GRCh37 Chromosome 7, 22984824: 22984824
36 FAM126A NM_032581.3(FAM126A): c.1515A> G (p.Gln505=) single nucleotide variant Uncertain significance rs373948210 GRCh38 Chromosome 7, 22945640: 22945640
37 FAM126A NM_032581.3(FAM126A): c.1515A> G (p.Gln505=) single nucleotide variant Uncertain significance rs373948210 GRCh37 Chromosome 7, 22985259: 22985259
38 FAM126A NM_032581.3(FAM126A): c.991+11C> T single nucleotide variant Uncertain significance rs141187440 GRCh38 Chromosome 7, 22960245: 22960245
39 FAM126A NM_032581.3(FAM126A): c.991+11C> T single nucleotide variant Uncertain significance rs141187440 GRCh37 Chromosome 7, 22999864: 22999864
40 FAM126A NM_032581.3(FAM126A): c.626+5A> G single nucleotide variant Uncertain significance rs778280191 GRCh38 Chromosome 7, 22976205: 22976205
41 FAM126A NM_032581.3(FAM126A): c.626+5A> G single nucleotide variant Uncertain significance rs778280191 GRCh37 Chromosome 7, 23015824: 23015824
42 FAM126A NM_032581.3(FAM126A): c.-29+4A> T single nucleotide variant Uncertain significance rs886062213 GRCh37 Chromosome 7, 23053540: 23053540
43 FAM126A NM_032581.3(FAM126A): c.-29+4A> T single nucleotide variant Uncertain significance rs886062213 GRCh38 Chromosome 7, 23013921: 23013921
44 FAM126A NM_032581.3(FAM126A): c.-111G> A single nucleotide variant Likely benign rs183608311 GRCh37 Chromosome 7, 23053626: 23053626
45 FAM126A NM_032581.3(FAM126A): c.-111G> A single nucleotide variant Likely benign rs183608311 GRCh38 Chromosome 7, 23014007: 23014007
46 FAM126A NM_032581.3(FAM126A): c.*3878C> T single nucleotide variant Uncertain significance rs886062197 GRCh38 Chromosome 7, 22941711: 22941711
47 FAM126A NM_032581.3(FAM126A): c.*3878C> T single nucleotide variant Uncertain significance rs886062197 GRCh37 Chromosome 7, 22981330: 22981330
48 FAM126A NM_032581.3(FAM126A): c.*3804A> C single nucleotide variant Benign rs34683819 GRCh38 Chromosome 7, 22941785: 22941785
49 FAM126A NM_032581.3(FAM126A): c.*3804A> C single nucleotide variant Benign rs34683819 GRCh37 Chromosome 7, 22981404: 22981404
50 FAM126A NM_032581.3(FAM126A): c.*3266C> T single nucleotide variant Likely benign rs75393023 GRCh38 Chromosome 7, 22942323: 22942323

Expression for Leukodystrophy, Hypomyelinating, 5

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 5.

Pathways for Leukodystrophy, Hypomyelinating, 5

GO Terms for Leukodystrophy, Hypomyelinating, 5

Cellular components related to Leukodystrophy, Hypomyelinating, 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 myelin sheath GO:0043209 8.62 PLP1 TUBB4A

Biological processes related to Leukodystrophy, Hypomyelinating, 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 myelination GO:0042552 8.62 FAM126A PLP1

Sources for Leukodystrophy, Hypomyelinating, 5

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59 OMIM via Orphanet
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