MCID: HMC020
MIFTS: 30

Homocystinuria, B6-Responsive and Nonresponsive Types

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

Aliases & Classifications for Homocystinuria, B6-Responsive and Nonresponsive Types

MalaCards integrated aliases for Homocystinuria, B6-Responsive and Nonresponsive Types:

Name: Homocystinuria, B6-Responsive and Nonresponsive Types 54 13
Homocystinuria Due to Cystathionine Beta-Synthase Deficiency 56 71
Cystathionine Beta-Synthase Deficiency 56 71
Homocystinuria with or Without Response to Pyridoxine 71
Cystathionine Beta-Synthase Deficiency Disease 69
Hyperhomocysteinemia Thrombotic Cbs-Related 71
Thrombosis, Hyperhomocysteinemic 54
Classic Homocystinuria 56
Cbs Deficiency 71
Cbsd 71

Characteristics:

Orphanet epidemiological data:

56
classic homocystinuria
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe); Age of onset: Childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
fifty-percent of individuals responsive to pyridoxine (vitamin b6)
pyridoxine responsive individuals often have milder manifestations than those not responsive
management of homocystinuria includes low methionine, cystine supplemented diet for pyridoxine nonresponders and pyridoxine supplementation for pyridoxine responders
treatment with betaine, especially for pyridoxine nonresponders
thromboembolism is the most common cause of death
frequency between 1 in 58,000 to 1 in 1,000,000


HPO:

32
homocystinuria, b6-responsive and nonresponsive types:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Homocystinuria, B6-Responsive and Nonresponsive Types

OMIM : 54
Classic homocystinuria is an autosomal recessive metabolic disorder of sulfur metabolism. The clinical features of untreated homocystinuria due to CBS deficiency usually manifest in the first or second decade of life and include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome (MFS; 154700), and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine. There are 2 main phenotypes of the classic disorder: a milder pyridoxine (vitamin B6)-responsive form, and a more severe pyridoxine-nonresponsive form. Pyridoxine is a cofactor for the CBS enzyme, and can aid in the conversion of homocysteine to cysteine (summary by Reish et al., 1995 and Testai and Gorelick, 2010). Some patients have been reported to have a milder form of homocystinuria, which is characterized by increased plasma homocysteine and increased risk for thrombotic events in young adulthood, but without the other skeletal, ocular, or nervous system manifestations observed in classic homocystinuria (Kelly et al., 2003). (236200)

MalaCards based summary : Homocystinuria, B6-Responsive and Nonresponsive Types, also known as homocystinuria due to cystathionine beta-synthase deficiency, is related to homocystinuria caused by cystathionine beta-synthase deficiency and homocystinuria due to cbs deficiency, and has symptoms including myopia, seizures and glaucoma. An important gene associated with Homocystinuria, B6-Responsive and Nonresponsive Types is CBS (Cystathionine-Beta-Synthase). Affiliated tissues include skin, liver and eye.

UniProtKB/Swiss-Prot : 71 Cystathionine beta-synthase deficiency: An enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria. The clinical features of untreated homocystinuria due to CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine.

Related Diseases for Homocystinuria, B6-Responsive and Nonresponsive Types

Diseases related to Homocystinuria, B6-Responsive and Nonresponsive Types via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 homocystinuria caused by cystathionine beta-synthase deficiency 12.5
2 homocystinuria due to cbs deficiency 12.2
3 homocystinuria 11.7
4 atherosclerosis 9.7
5 hepatitis 9.7
6 cerebritis 9.7
7 hyperhomocysteinemia 9.7

Graphical network of the top 20 diseases related to Homocystinuria, B6-Responsive and Nonresponsive Types:



Diseases related to Homocystinuria, B6-Responsive and Nonresponsive Types

Symptoms & Phenotypes for Homocystinuria, B6-Responsive and Nonresponsive Types

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Mouth:
high-arched palate

Head And Neck- Eyes:
myopia
glaucoma
ectopia lentis

Skeletal- Spine:
kyphoscoliosis
biconcave 'codfish' vertebrae

Neurologic- Behavioral Psychiatric Manifestations:
depression
psychiatric disorders
personality disorder

Abdomen- Pancreas:
pancreatitis

Skin Nails & Hair- Hair:
hypopigmentation
fine, brittle hair

Cardiovascular- Heart:
mitral valve prolapse
myocardial infarction

Skeletal:
generalized osteoporosis

Growth- Other:
occasional failure to thrive in infancy

Hematology:
thromboembolism (25%)

Neurologic- Central Nervous System:
mental retardation
seizures
cerebrovascular accident

Laboratory- Abnormalities:
homocystinuria
methioninuria
cystathionine beta-synthase deficiency

Chest- Ribs Sternum Clavicles And Scapulae:
pectus carinatum
pectus excavatum

Abdomen- External Features:
inguinal hernia

Skin Nails & Hair- Skin:
hypopigmentation
livedo reticularis
malar flush

Head And Neck- Teeth:
crowded teeth

Skeletal- Limbs:
arachnodactyly
dolichostenomelia
limited joint mobility

Growth- Height:
normal to tall stature

Abdomen- Liver:
fatty changes in liver


Clinical features from OMIM:

236200

Human phenotypes related to Homocystinuria, B6-Responsive and Nonresponsive Types:

56 32 (show top 50) (show all 61)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 myopia 56 32 Frequent (79-30%) HP:0000545
2 seizures 56 32 Occasional (29-5%) HP:0001250
3 glaucoma 56 32 Occasional (29-5%) HP:0000501
4 pectus carinatum 56 32 Frequent (79-30%) HP:0000768
5 intellectual disability 56 32 Very frequent (99-80%) HP:0001249
6 pectus excavatum 56 32 Frequent (79-30%) HP:0000767
7 high palate 56 32 Occasional (29-5%) HP:0000218
8 arachnodactyly 56 32 Very frequent (99-80%) HP:0001166
9 ectopia lentis 56 32 Very frequent (99-80%) HP:0001083
10 dental crowding 56 32 Very frequent (99-80%) HP:0000678
11 disproportionate tall stature 56 32 Very frequent (99-80%) HP:0001519
12 failure to thrive 32 occasional (7.5%) HP:0001508
13 scoliosis 56 Frequent (79-30%)
14 sparse scalp hair 56 Frequent (79-30%)
15 optic atrophy 56 Occasional (29-5%)
16 retinal detachment 56 Occasional (29-5%)
17 hepatomegaly 56 Occasional (29-5%)
18 thromboembolism 32 HP:0001907
19 homocystinuria 32 HP:0002156
20 hernia 56 Occasional (29-5%)
21 kyphosis 56 Frequent (79-30%)
22 brittle hair 32 HP:0002299
23 kyphoscoliosis 32 HP:0002751
24 osteoporosis 56 Very frequent (99-80%)
25 genu valgum 56 Frequent (79-30%)
26 depression 32 HP:0000716
27 cutis marmorata 32 HP:0000965
28 inguinal hernia 32 HP:0000023
29 pancreatitis 32 HP:0001733
30 cataract 56 Occasional (29-5%)
31 recurrent fractures 56 Very frequent (99-80%)
32 psychosis 56 Occasional (29-5%)
33 hypertension 56 Frequent (79-30%)
34 amblyopia 56 Frequent (79-30%)
35 hepatic steatosis 32 HP:0001397
36 joint stiffness 56 Frequent (79-30%)
37 stroke 32 HP:0001297
38 venous thrombosis 56 Frequent (79-30%)
39 pulmonary embolism 56 Frequent (79-30%)
40 mitral valve prolapse 32 HP:0001634
41 tall stature 32 HP:0000098
42 myocardial infarction 32 HP:0001658
43 arterial thrombosis 56 Frequent (79-30%)
44 generalized osteoporosis 32 HP:0040160
45 arteriovenous malformation 56 Frequent (79-30%)
46 urticaria 56 Occasional (29-5%)
47 anorexia 56 Occasional (29-5%)
48 intracranial hemorrhage 56 Occasional (29-5%)
49 cerebral ischemia 56 Frequent (79-30%)
50 elevated hepatic transaminases 56 Occasional (29-5%)

UMLS symptoms related to Homocystinuria, B6-Responsive and Nonresponsive Types:


seizures

Drugs & Therapeutics for Homocystinuria, B6-Responsive and Nonresponsive Types

Search Clinical Trials , NIH Clinical Center for Homocystinuria, B6-Responsive and Nonresponsive Types

Genetic Tests for Homocystinuria, B6-Responsive and Nonresponsive Types

Anatomical Context for Homocystinuria, B6-Responsive and Nonresponsive Types

MalaCards organs/tissues related to Homocystinuria, B6-Responsive and Nonresponsive Types:

39
Skin, Liver, Eye

Publications for Homocystinuria, B6-Responsive and Nonresponsive Types

Variations for Homocystinuria, B6-Responsive and Nonresponsive Types

UniProtKB/Swiss-Prot genetic disease variations for Homocystinuria, B6-Responsive and Nonresponsive Types:

71 (show top 50) (show all 104)
id Symbol AA change Variation ID SNP ID
1 CBS p.Pro78Arg VAR_002171 rs786204608
2 CBS p.Pro88Ser VAR_002172
3 CBS p.Lys102Asn VAR_002173 rs786204609
4 CBS p.Ala114Val VAR_002174 rs121964964
5 CBS p.Arg125Gln VAR_002175 rs781444670
6 CBS p.Glu131Asp VAR_002176
7 CBS p.Glu144Lys VAR_002177 rs121964966
8 CBS p.Pro145Leu VAR_002178 rs121964963
9 CBS p.Cys165Tyr VAR_002179
10 CBS p.Val168Met VAR_002180 rs121964970
11 CBS p.Arg224His VAR_002181 rs761647392
12 CBS p.Glu239Lys VAR_002182
13 CBS p.Thr257Met VAR_002183 rs758236584
14 CBS p.Ile278Thr VAR_002184 rs5742905
15 CBS p.Pro290Leu VAR_002185 rs760912339
16 CBS p.Gly307Ser VAR_002186 rs121964962
17 CBS p.Ala331Val VAR_002187
18 CBS p.Arg336Cys VAR_002188 rs398123151
19 CBS p.Arg369His VAR_002189 rs11700812
20 CBS p.Val371Met VAR_002190 rs372010465
21 CBS p.Lys384Glu VAR_002191 rs121964967
22 CBS p.Asp444Asn VAR_002192 rs28934891
23 CBS p.Val454Glu VAR_002193
24 CBS p.Leu539Ser VAR_002194 rs121964968
25 CBS p.Pro49Leu VAR_008049 rs148865119
26 CBS p.Arg58Trp VAR_008050 rs555959266
27 CBS p.Gly85Arg VAR_008051 rs863223435
28 CBS p.Lys102Gln VAR_008052 rs34040148
29 CBS p.Gly116Arg VAR_008053 rs760214620
30 CBS p.Arg121Cys VAR_008054 rs775992753
31 CBS p.Arg121His VAR_008055 rs770095972
32 CBS p.Arg121Leu VAR_008056 rs770095972
33 CBS p.Arg125Trp VAR_008057
34 CBS p.Met126Val VAR_008058
35 CBS p.Glu128Asp VAR_008059
36 CBS p.Gly139Arg VAR_008060 rs121964965
37 CBS p.Gly148Arg VAR_008061 rs755952006
38 CBS p.Gly151Arg VAR_008062 rs373782713
39 CBS p.Ile152Met VAR_008064
40 CBS p.Ala155Thr VAR_008065
41 CBS p.Glu176Lys VAR_008066
42 CBS p.Val180Ala VAR_008067
43 CBS p.Thr191Met VAR_008068 rs121964973
44 CBS p.Asp198Val VAR_008069
45 CBS p.Ala226Thr VAR_008070
46 CBS p.Asp234Asn VAR_008071 rs773734233
47 CBS p.Thr262Met VAR_008072 rs149119723
48 CBS p.Arg266Gly VAR_008073
49 CBS p.Arg266Lys VAR_008074 rs28934275
50 CBS p.Glu302Lys VAR_008076 rs779270933

ClinVar genetic disease variations for Homocystinuria, B6-Responsive and Nonresponsive Types:

6 (show all 48)
id Gene Variation Type Significance SNP ID Assembly Location
1 CBS NM_000071.2(CBS): c.919G> A (p.Gly307Ser) single nucleotide variant Pathogenic rs121964962 GRCh37 Chromosome 21, 44483098: 44483098
2 CBS NM_000071.2(CBS): c.341C> T (p.Ala114Val) single nucleotide variant Pathogenic/Likely pathogenic rs121964964 GRCh37 Chromosome 21, 44486463: 44486463
3 CBS NM_000071.2(CBS): c.833T> C (p.Ile278Thr) single nucleotide variant Pathogenic rs5742905 GRCh37 Chromosome 21, 44483184: 44483184
4 CBS NM_000071.2(CBS): c.430G> A (p.Glu144Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121964966 GRCh37 Chromosome 21, 44486374: 44486374
5 CBS NM_000071.2(CBS): c.797G> A (p.Arg266Lys) single nucleotide variant Pathogenic rs121964969 GRCh37 Chromosome 21, 44484041: 44484041
6 CBS NM_000071.2(CBS): c.1330G> A (p.Asp444Asn) single nucleotide variant Pathogenic rs28934891 GRCh37 Chromosome 21, 44478972: 44478972
7 CBS NM_000071.2(CBS): c.1224-2A> C single nucleotide variant Pathogenic rs375846341 GRCh37 Chromosome 21, 44479080: 44479080
8 CBS NM_000071.2(CBS): c.1265C> T (p.Pro422Leu) single nucleotide variant Pathogenic rs28934892 GRCh37 Chromosome 21, 44479037: 44479037
9 CBS NM_000071.2(CBS): c.1397C> T (p.Ser466Leu) single nucleotide variant Pathogenic rs121964971 GRCh37 Chromosome 21, 44478325: 44478325
10 CBS NM_000071.2(CBS): c.1058C> T (p.Thr353Met) single nucleotide variant Pathogenic/Likely pathogenic rs121964972 GRCh37 Chromosome 21, 44480638: 44480638
11 CBS NM_000071.2(CBS): c.1006C> T (p.Arg336Cys) single nucleotide variant Pathogenic rs398123151 GRCh37 Chromosome 21, 44482454: 44482454
12 CBS NM_000071.2(CBS): c.1566delG (p.Lys523Serfs) deletion Likely pathogenic rs786204466 GRCh37 Chromosome 21, 44474080: 44474080
13 CBS NM_000071.2(CBS): c.1358+1G> A single nucleotide variant Likely pathogenic rs786204679 GRCh38 Chromosome 21, 43058833: 43058833
14 CBS NM_000071.2(CBS): c.1136G> A (p.Arg379Gln) single nucleotide variant Pathogenic/Likely pathogenic rs763036586 GRCh37 Chromosome 21, 44480560: 44480560
15 CBS NM_000071.2(CBS): c.1039G> A (p.Gly347Ser) single nucleotide variant Pathogenic/Likely pathogenic rs771298943 GRCh37 Chromosome 21, 44482421: 44482421
16 CBS NM_000071.2(CBS): c.770C> T (p.Thr257Met) single nucleotide variant Pathogenic/Likely pathogenic rs758236584 GRCh37 Chromosome 21, 44484068: 44484068
17 CBS NM_000071.2(CBS): c.689delT (p.Leu230Argfs) deletion Pathogenic/Likely pathogenic rs775351239 GRCh37 Chromosome 21, 44485360: 44485360
18 CBS NM_000071.2(CBS): c.667-14_667-7del8 deletion Pathogenic/Likely pathogenic rs764160782 GRCh37 Chromosome 21, 44485389: 44485396
19 CBS NM_000071.2(CBS): c.362G> A (p.Arg121His) single nucleotide variant Likely pathogenic rs770095972 GRCh38 Chromosome 21, 43066332: 43066332
20 CBS NM_000071.2(CBS): c.346G> A (p.Gly116Arg) single nucleotide variant Likely pathogenic rs760214620 GRCh37 Chromosome 21, 44486458: 44486458
21 CBS NM_000071.2(CBS): c.306G> C (p.Lys102Asn) single nucleotide variant Likely pathogenic rs786204609 GRCh37 Chromosome 21, 44488629: 44488629
22 CBS NM_000071.2(CBS): c.302T> C (p.Leu101Pro) single nucleotide variant Likely pathogenic rs786204757 GRCh37 Chromosome 21, 44488633: 44488633
23 CBS NM_000071.2(CBS): c.233C> G (p.Pro78Arg) single nucleotide variant Likely pathogenic rs786204608 GRCh37 Chromosome 21, 44488702: 44488702
24 CBS NM_000071.2(CBS): c.1218delG (p.Lys406Asnfs) deletion Pathogenic rs794727083 GRCh37 Chromosome 21, 44479341: 44479341
25 CBS NM_000071.2(CBS): c.374G> A (p.Arg125Gln) single nucleotide variant Pathogenic rs781444670 GRCh37 Chromosome 21, 44486430: 44486430
26 CBS NM_000071.2(CBS): c.785C> T (p.Thr262Met) single nucleotide variant Pathogenic/Likely pathogenic rs149119723 GRCh37 Chromosome 21, 44484053: 44484053
27 PKHD1 NM_138694.3(PKHD1): c.5023delG (p.Ala1675Profs) deletion Likely pathogenic rs797044607 GRCh37 Chromosome 6, 51889585: 51889585
28 CBS NM_000071.2(CBS): c.1111G> A (p.Val371Met) single nucleotide variant Pathogenic/Likely pathogenic rs372010465 GRCh37 Chromosome 21, 44480585: 44480585
29 CBS NM_000071.2(CBS): c.969G> A (p.Trp323Ter) single nucleotide variant Pathogenic rs863223432 GRCh37 Chromosome 21, 44482491: 44482491
30 CBS NM_000071.2(CBS): c.162G> A (p.Trp54Ter) single nucleotide variant Likely pathogenic rs199948079 GRCh37 Chromosome 21, 44492142: 44492142
31 CBS NM_000071.2(CBS): c.146C> T (p.Pro49Leu) single nucleotide variant Pathogenic/Likely pathogenic rs148865119 GRCh37 Chromosome 21, 44492158: 44492158
32 CBS NM_000071.2(CBS): c.28delG (p.Val10Trpfs) deletion Pathogenic/Likely pathogenic rs779250698 GRCh37 Chromosome 21, 44492276: 44492276
33 CBS NM_000071.2(CBS): c.1468-1G> A single nucleotide variant Likely pathogenic rs1057516895 GRCh38 Chromosome 21, 43056888: 43056888
34 CBS NM_000071.2(CBS): c.1321A> T (p.Lys441Ter) single nucleotide variant Likely pathogenic rs1057516645 GRCh38 Chromosome 21, 43058871: 43058871
35 CBS NM_000071.2(CBS): c.1007G> A (p.Arg336His) single nucleotide variant Likely pathogenic rs760417941 GRCh37 Chromosome 21, 44482453: 44482453
36 CBS NM_000071.2(CBS): c.959T> C (p.Val320Ala) single nucleotide variant Likely pathogenic rs781567152 GRCh38 Chromosome 21, 43062391: 43062391
37 CBS NM_000071.2(CBS): c.954+1G> A single nucleotide variant Pathogenic rs1057517373 GRCh37 Chromosome 21, 44483062: 44483062
38 CBS NM_000071.2(CBS): c.903C> G (p.Tyr301Ter) single nucleotide variant Likely pathogenic rs746575551 GRCh37 Chromosome 21, 44483114: 44483114
39 CBS NM_000071.2(CBS): c.738delG (p.Lys247Serfs) deletion Pathogenic/Likely pathogenic rs766453711 GRCh37 Chromosome 21, 44484100: 44484100
40 CBS NM_000071.2(CBS): c.707_708delCCinsGGTG (p.Thr236Argfs) indel Likely pathogenic rs1057517435 GRCh37 Chromosome 21, 44485341: 44485342
41 CBS NM_000071.2(CBS): c.676G> A (p.Ala226Thr) single nucleotide variant Likely pathogenic rs763835246 GRCh37 Chromosome 21, 44485373: 44485373
42 CBS NM_000071.2(CBS): c.467delT (p.Leu156Argfs) deletion Likely pathogenic rs767036273 GRCh37 Chromosome 21, 44485790: 44485790
43 CBS NM_000071.2(CBS): c.442G> A (p.Gly148Arg) single nucleotide variant Likely pathogenic rs755952006 GRCh38 Chromosome 21, 43066252: 43066252
44 CBS NM_000071.2(CBS): c.402delG (p.Thr135Argfs) deletion Likely pathogenic rs1057517083 GRCh37 Chromosome 21, 44486402: 44486402
45 CBS NM_000071.2(CBS): c.316+1G> A single nucleotide variant Likely pathogenic rs1057516256 GRCh37 Chromosome 21, 44488618: 44488618
46 CBS NM_000071.2(CBS): c.209+1G> C single nucleotide variant Likely pathogenic rs751464024 GRCh38 Chromosome 21, 43071984: 43071984
47 CBS NM_000071.2(CBS): c.18_36del19 (p.Glu9Alafs) deletion Likely pathogenic rs1057516552 GRCh37 Chromosome 21, 44492268: 44492286
48 CBS NM_000071.2(CBS): c.19dupC (p.Gln7Profs) duplication Pathogenic rs1057517198 GRCh37 Chromosome 21, 44492285: 44492285

Expression for Homocystinuria, B6-Responsive and Nonresponsive Types

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