OPLAHD
MCID: 5XP001
MIFTS: 30

5-Oxoprolinase Deficiency (OPLAHD)

Categories: Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for 5-Oxoprolinase Deficiency

MalaCards integrated aliases for 5-Oxoprolinase Deficiency:

Name: 5-Oxoprolinase Deficiency 57 20 58 72 36 29 13 6 39 70
Oxoprolinuria Due to 5-Oxoprolinase Deficiency 57 20
Oxoprolinuria Due to Oxoprolinase Deficiency 58 72
Oplahd 57 72
5-Alpha-Oxoprolinase Deficiency 20

Characteristics:

Orphanet epidemiological data:

58
5-oxoprolinase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
some patients are clinically unaffected.


HPO:

31
5-oxoprolinase deficiency:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

OMIM® 57 260005
KEGG 36 H02313
MeSH 44 D000592
MESH via Orphanet 45 C535322
ICD10 via Orphanet 33 E72.8
UMLS via Orphanet 71 C0268525
Orphanet 58 ORPHA33572
MedGen 41 C0268525
UMLS 70 C0268525

Summaries for 5-Oxoprolinase Deficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 33572 Definition A very heterogeneous condition characterized by 5-oxoprolinuria. Epidemiology It has been detected in eight patients worldwide. All affected patients have been identified because of 5-oxoprolinuria. Clinical description Symptoms reported in individual patients include renal stone formation, enterocolitis, intellectual deficiency, neonatal hypoglycemia, microcytic anemia and microcephaly. Etiology 5-Oxoprolinase catalyses a step in the gamma-glutamyl cycle (glutathione metabolism). Diagnostic methods The diagnosis is based on the finding of 5-oxoprolinuria and on the low activity of 5-oxoprolinase. Differential diagnosis Other causes of 5-oxoprolinuria include glutathione synthetase deficiency (see this term), diet (certain infant formulas and tomato juice), severe burns, Stevens-Johnson syndrome (see this term), inborn errors of metabolism not involving the gamma-glutamyl cycle, e.g. X-linked ornithine trancarbamylase deficiency, urea cycle defects, or tyrosinemia, as well as homocystinuria (see these terms), drug metabolism (paracetamol, vigabatrin, flucloxacillin, netilmicin), prematurity, malnutrition, pregnancy and nephropatic cystinosis. Genetic counseling The disease is transmitted as an autosomal recessive trait. Management and treatment No specific treatment has been proposed or tested. Prognosis The prognosis is difficult to predict as only eight patients with different clinical symptoms have been described.

MalaCards based summary : 5-Oxoprolinase Deficiency, also known as oxoprolinuria due to 5-oxoprolinase deficiency, is related to glutathione synthetase deficiency and nephrolithiasis, calcium oxalate, and has symptoms including vomiting, abdominal pain and diarrhea. An important gene associated with 5-Oxoprolinase Deficiency is OPLAH (5-Oxoprolinase, ATP-Hydrolysing), and among its related pathways/superpathways is Glutathione metabolism. Related phenotypes are vomiting and abdominal pain

OMIM® : 57 5-Oxoprolinuria can be caused by genetic defects in either of 2 enzymes involved in the gamma-glutamyl cycle of glutathione metabolism: glutathione synthetase (GSS; 601002) or 5-oxoprolinase (OPLAH; 614243). GSS deficiency (266130) is best characterized as an inborn error of glutathione metabolism, but there is debate as to whether OPLAH deficiency represents a disorder or simply a biochemical condition with no adverse clinical effects because patients lack a consistent clinical picture apart from 5-oxoprolinuria (summary by Calpena et al., 2013). (260005) (Updated 05-Apr-2021)

KEGG : 36 5-Oxoprolinase deficiency is an extremely rare disorder of the gamma-glutamyl cycle, that represents the primary pathway for glutathione synthesis and degradation. Recently, the OPLAH mutation was reported in two siblings who suffered from 5-oxoprolinuria with a benign clinical course.

UniProtKB/Swiss-Prot : 72 5-oxoprolinase deficiency: A disorder characterized by calcium oxalate/carbonate urolithiasis, and excessive urinary 5-oxo-L-proline. Affected individuals have recurrent episodes of vomiting, diarrhea, and abdominal pain.

Related Diseases for 5-Oxoprolinase Deficiency

Diseases related to 5-Oxoprolinase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 glutathione synthetase deficiency 11.2
2 nephrolithiasis, calcium oxalate 10.1
3 enterocolitis 10.1
4 rett syndrome 10.1
5 autosomal recessive disease 10.1
6 urolithiasis 10.1
7 microcephaly 10.1
8 diarrhea 10.1
9 nephrolithiasis 10.1
10 encephalopathy 10.1
11 disorder of the gamma-glutamyl cycle 10.1

Graphical network of the top 20 diseases related to 5-Oxoprolinase Deficiency:



Diseases related to 5-Oxoprolinase Deficiency

Symptoms & Phenotypes for 5-Oxoprolinase Deficiency

Human phenotypes related to 5-Oxoprolinase Deficiency:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 vomiting 31 HP:0002013
2 abdominal pain 31 HP:0002027
3 diarrhea 31 HP:0002014
4 prolinuria 31 HP:0003137
5 enterocolitis 31 HP:0004387
6 calcium oxalate nephrolithiasis 31 HP:0008672
7 reduced 5-oxoprolinase level 31 HP:0040142
8 increased level of l-pyroglutamic acid in urine 31 HP:0410132

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Abdomen Gastrointestinal:
vomiting
diarrhea
enterocolitis

Genitourinary Kidneys:
calcium oxalate/carbonate urolithiasis

Abdomen:
abdominal pain

Laboratory Abnormalities:
excessive urinary 5-oxo-l-proline
5-oxoprolinase deficiency

Clinical features from OMIM®:

260005 (Updated 05-Apr-2021)

UMLS symptoms related to 5-Oxoprolinase Deficiency:


vomiting; abdominal pain; diarrhea

Drugs & Therapeutics for 5-Oxoprolinase Deficiency

Search Clinical Trials , NIH Clinical Center for 5-Oxoprolinase Deficiency

Genetic Tests for 5-Oxoprolinase Deficiency

Genetic tests related to 5-Oxoprolinase Deficiency:

# Genetic test Affiliating Genes
1 5-Oxoprolinase Deficiency 29 OPLAH

Anatomical Context for 5-Oxoprolinase Deficiency

Publications for 5-Oxoprolinase Deficiency

Articles related to 5-Oxoprolinase Deficiency:

(show all 19)
# Title Authors PMID Year
1
Unravelling 5-oxoprolinuria (pyroglutamic aciduria) due to bi-allelic OPLAH mutations: 20 new mutations in 14 families. 57 6 61
27477828 2016
2
5-Oxoprolinase deficiency: report of the first human OPLAH mutation. 57 6 61
21651516 2012
3
5-Oxoprolinuria in Heterozygous Patients for 5-Oxoprolinase (OPLAH) Missense Changes. 57 6
23430506 2013
4
5-Oxoprolinuria associated with 5-oxoprolinase deficiency; further evidence that this is a benign disorder. 61 57
8127060 1993
5
5-oxoprolinuria due to hereditary 5-oxoprolinase deficiency in two brothers--a new inborn error of the gamma-glutamyl cycle. 61 57
6113726 1981
6
Pyroglutamic aciduria (5-oxoprolinuria) without glutathione synthetase deficiency and with decreased pyroglutamate hydrolase activity. 57
6790862 1981
7
Acetaminophen Use Concomitant with Long-Lasting Flucloxacillin Therapy: A Dangerous Combination. 61
32665925 2020
8
Five Chinese patients with 5-oxoprolinuria due to glutathione synthetase and 5-oxoprolinase deficiencies. 61
25851806 2015
9
New insights into the genetics of 5-oxoprolinase deficiency and further evidence that it is a benign biochemical condition. 61
25129617 2015
10
Pyroglutamic acid-induced metabolic acidosis: a case report. 61
24694265 2014
11
Coma, metabolic acidosis, and methemoglobinemia in a patient with acetaminophen toxicity. 61
24077426 2013
12
Inborn errors in the metabolism of glutathione. 61
17397529 2007
13
A newborn infant with generalized glutathione synthetase deficiency. 61
15074378 2004
14
Clinical, biochemical, and molecular characterization of patients with glutathione synthetase deficiency. 61
10450861 1999
15
5-Oxoprolinuria in patients with and without defects in the gamma-glutamyl cycle. 61
10094443 1999
16
Patients with genetic defects in the gamma-glutamyl cycle. 61
9679548 1998
17
[5-Oxoprolinase deficiency]. 61
9590071 1998
18
Growth failure, encephalopathy, and endocrine dysfunctions in two siblings, one with 5-oxoprolinase deficiency. 61
9453376 1997
19
5-Oxoprolinase deficiency associated with severe psychomotor developmental delay, failure to thrive, microcephaly and microcytic anaemia. 61
7542714 1995

Variations for 5-Oxoprolinase Deficiency

ClinVar genetic disease variations for 5-Oxoprolinase Deficiency:

6 (show all 50)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 OPLAH NM_017570.5(OPLAH):c.969C>A (p.Ser323Arg) SNV Pathogenic 39635 rs398122906 GRCh37: 8:145113032-145113032
GRCh38: 8:144058129-144058129
2 OPLAH NM_017570.5(OPLAH):c.493C>T (p.Gln165Ter) SNV Pathogenic 856398 GRCh37: 8:145113770-145113770
GRCh38: 8:144058867-144058867
3 OPLAH NM_017570.5(OPLAH):c.2557C>T (p.Arg853Ter) SNV Pathogenic 572337 rs543486699 GRCh37: 8:145109593-145109593
GRCh38: 8:144054690-144054690
4 OPLAH NM_017570.5(OPLAH):c.2608dup (p.His870fs) Duplication Pathogenic 31133 rs781956288 GRCh37: 8:145109541-145109542
GRCh38: 8:144054638-144054639
5 OPLAH NM_017570.5(OPLAH):c.587+1G>A SNV Pathogenic 861806 GRCh37: 8:145113675-145113675
GRCh38: 8:144058772-144058772
6 OPLAH NM_017570.5(OPLAH):c.2987dup (p.Arg997fs) Duplication Pathogenic 955289 GRCh37: 8:145107916-145107917
GRCh38: 8:144053013-144053014
7 OPLAH NM_017570.5(OPLAH):c.1336_1337del (p.Ser446fs) Deletion Pathogenic 1029474 GRCh37: 8:145112436-145112437
GRCh38: 8:144057533-144057534
8 OPLAH NM_017570.5(OPLAH):c.3250C>T (p.Gln1084Ter) SNV Pathogenic 1033427 GRCh37: 8:145107405-145107405
GRCh38: 8:144052502-144052502
9 OPLAH NM_017570.5(OPLAH):c.3509dup (p.Arg1171fs) Duplication Pathogenic 1033428 GRCh37: 8:145106929-145106930
GRCh38: 8:144052028-144052029
10 OPLAH NM_017570.5(OPLAH):c.659C>T (p.Ser220Leu) SNV Likely pathogenic 1048076 GRCh37: 8:145113523-145113523
GRCh38: 8:144058620-144058620
11 OPLAH NM_017570.5(OPLAH):c.3265G>A (p.Val1089Ile) SNV Conflicting interpretations of pathogenicity 39636 rs185836803 GRCh37: 8:145107390-145107390
GRCh38: 8:144052487-144052487
12 OPLAH NM_017570.5(OPLAH):c.1424C>T (p.Ala475Val) SNV Uncertain significance 570470 rs374935079 GRCh37: 8:145112222-145112222
GRCh38: 8:144057319-144057319
13 OPLAH NM_017570.5(OPLAH):c.2473G>A (p.Gly825Arg) SNV Uncertain significance 578462 rs11777194 GRCh37: 8:145109753-145109753
GRCh38: 8:144054850-144054850
14 OPLAH NM_017570.5(OPLAH):c.2230C>T (p.Arg744Cys) SNV Uncertain significance 587493 rs371837669 GRCh37: 8:145110709-145110709
GRCh38: 8:144055806-144055806
15 OPLAH NM_017570.5(OPLAH):c.3352G>C (p.Glu1118Gln) SNV Uncertain significance 634613 rs1426386645 GRCh37: 8:145107181-145107181
GRCh38: 8:144052278-144052278
16 OPLAH NM_017570.5(OPLAH):c.1340C>T (p.Pro447Leu) SNV Uncertain significance 643594 rs782808832 GRCh37: 8:145112433-145112433
GRCh38: 8:144057530-144057530
17 OPLAH NM_017570.5(OPLAH):c.2669G>C (p.Gly890Ala) SNV Uncertain significance 650875 rs781927871 GRCh37: 8:145109481-145109481
GRCh38: 8:144054578-144054578
18 OPLAH NM_017570.5(OPLAH):c.1972C>T (p.Arg658Trp) SNV Uncertain significance 652843 rs782702109 GRCh37: 8:145111299-145111299
GRCh38: 8:144056396-144056396
19 OPLAH NM_017570.5(OPLAH):c.430C>T (p.Arg144Cys) SNV Uncertain significance 657572 rs782533601 GRCh37: 8:145113916-145113916
GRCh38: 8:144059013-144059013
20 OPLAH NM_017570.5(OPLAH):c.3518G>A (p.Arg1173His) SNV Uncertain significance 661332 rs782094303 GRCh37: 8:145106921-145106921
GRCh38: 8:144052020-144052020
21 OPLAH NM_017570.5(OPLAH):c.1372G>A (p.Val458Met) SNV Uncertain significance 735200 rs144920839 GRCh37: 8:145112401-145112401
GRCh38: 8:144057498-144057498
22 OPLAH NM_017570.5(OPLAH):c.1850T>C (p.Met617Thr) SNV Uncertain significance 1033426 GRCh37: 8:145111421-145111421
GRCh38: 8:144056518-144056518
23 OPLAH NM_017570.5(OPLAH):c.1438C>T (p.Pro480Ser) SNV Uncertain significance 1008355 GRCh37: 8:145112208-145112208
GRCh38: 8:144057305-144057305
24 OPLAH NM_017570.5(OPLAH):c.1258C>T (p.Pro420Ser) SNV Uncertain significance 580604 rs1564292461 GRCh37: 8:145112515-145112515
GRCh38: 8:144057612-144057612
25 OPLAH NM_017570.5(OPLAH):c.843C>G (p.Ser281Arg) SNV Uncertain significance 835652 GRCh37: 8:145113248-145113248
GRCh38: 8:144058345-144058345
26 OPLAH NM_017570.5(OPLAH):c.2973C>G (p.Asp991Glu) SNV Uncertain significance 844739 GRCh37: 8:145107931-145107931
GRCh38: 8:144053028-144053028
27 OPLAH NM_017570.5(OPLAH):c.1909C>T (p.Arg637Trp) SNV Uncertain significance 853743 GRCh37: 8:145111362-145111362
GRCh38: 8:144056459-144056459
28 OPLAH NM_017570.5(OPLAH):c.2654A>G (p.Lys885Arg) SNV Uncertain significance 963409 GRCh37: 8:145109496-145109496
GRCh38: 8:144054593-144054593
29 OPLAH NM_017570.5(OPLAH):c.1680T>G (p.Asp560Glu) SNV Uncertain significance 851753 GRCh37: 8:145111877-145111877
GRCh38: 8:144056974-144056974
30 OPLAH NM_017570.5(OPLAH):c.1939G>A (p.Glu647Lys) SNV Uncertain significance 966758 GRCh37: 8:145111332-145111332
GRCh38: 8:144056429-144056429
31 OPLAH NM_017570.5(OPLAH):c.135C>T (p.Asp45=) SNV Uncertain significance 946293 GRCh37: 8:145114801-145114801
GRCh38: 8:144059898-144059898
32 OPLAH NM_017570.5(OPLAH):c.272G>A (p.Arg91Gln) SNV Uncertain significance 958883 GRCh37: 8:145114593-145114593
GRCh38: 8:144059690-144059690
33 OPLAH NM_017570.5(OPLAH):c.1806G>A (p.Ser602=) SNV Uncertain significance 965734 GRCh37: 8:145111559-145111559
GRCh38: 8:144056656-144056656
34 OPLAH NM_017570.5(OPLAH):c.2096+8G>A SNV Likely benign 789619 rs372984548 GRCh37: 8:145111042-145111042
GRCh38: 8:144056139-144056139
35 OPLAH NM_017570.5(OPLAH):c.2792A>G (p.Gln931Arg) SNV Likely benign 790907 rs200702041 GRCh37: 8:145108191-145108191
GRCh38: 8:144053288-144053288
36 OPLAH NM_017570.5(OPLAH):c.2989C>T (p.Arg997Cys) SNV Likely benign 714717 rs200620019 GRCh37: 8:145107915-145107915
GRCh38: 8:144053012-144053012
37 OPLAH NM_017570.5(OPLAH):c.378T>G (p.Pro126=) SNV Likely benign 736214 rs1587567078 GRCh37: 8:145113968-145113968
GRCh38: 8:144059065-144059065
38 OPLAH NM_017570.5(OPLAH):c.171+6C>A SNV Likely benign 774252 rs117389174 GRCh37: 8:145114759-145114759
GRCh38: 8:144059856-144059856
39 OPLAH NM_017570.5(OPLAH):c.154C>T (p.Arg52Cys) SNV Likely benign 776394 rs182298526 GRCh37: 8:145114782-145114782
GRCh38: 8:144059879-144059879
40 OPLAH NM_017570.5(OPLAH):c.1502G>A (p.Arg501Gln) SNV Benign 779662 rs78071726 GRCh37: 8:145112144-145112144
GRCh38: 8:144057241-144057241
41 OPLAH NM_017570.5(OPLAH):c.1089-5C>T SNV Benign 779926 rs77001213 GRCh37: 8:145112831-145112831
GRCh38: 8:144057928-144057928
42 OPLAH NM_017570.5(OPLAH):c.471G>A (p.Thr157=) SNV Benign 785272 rs145079111 GRCh37: 8:145113792-145113792
GRCh38: 8:144058889-144058889
43 OPLAH NM_017570.5(OPLAH):c.3571C>T (p.Leu1191=) SNV Benign 776390 rs61740339 GRCh37: 8:145106868-145106868
GRCh38: 8:144051967-144051967
44 OPLAH NM_017570.5(OPLAH):c.2097-8C>T SNV Benign 776391 rs376189869 GRCh37: 8:145110850-145110850
GRCh38: 8:144055947-144055947
45 OPLAH NM_017570.5(OPLAH):c.805C>T (p.Arg269Cys) SNV Benign 776392 rs201078986 GRCh37: 8:145113286-145113286
GRCh38: 8:144058383-144058383
46 OPLAH NM_017570.5(OPLAH):c.402G>A (p.Leu134=) SNV Benign 776393 rs200748510 GRCh37: 8:145113944-145113944
GRCh38: 8:144059041-144059041
47 OPLAH NM_017570.5(OPLAH):c.2512-7C>A SNV Benign 718747 rs541135459 GRCh37: 8:145109645-145109645
GRCh38: 8:144054742-144054742
48 OPLAH NM_017570.5(OPLAH):c.2523G>A (p.Pro841=) SNV Benign 791681 rs187500280 GRCh37: 8:145109627-145109627
GRCh38: 8:144054724-144054724
49 OPLAH NM_017570.5(OPLAH):c.2964C>T (p.Asp988=) SNV Benign 529417 rs186192116 GRCh37: 8:145107940-145107940
GRCh38: 8:144053037-144053037
50 OPLAH NM_017570.5(OPLAH):c.3500_3501= (p.Gly1167=) Variation Benign 768272 GRCh37:
GRCh38: 8:144052037-144052038

Expression for 5-Oxoprolinase Deficiency

Search GEO for disease gene expression data for 5-Oxoprolinase Deficiency.

Pathways for 5-Oxoprolinase Deficiency

Pathways related to 5-Oxoprolinase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Glutathione metabolism hsa00480

GO Terms for 5-Oxoprolinase Deficiency

Sources for 5-Oxoprolinase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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