MCID: HYP111
MIFTS: 39

Hyperprolinemia

Categories: Blood diseases, Genetic diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hyperprolinemia

MalaCards integrated aliases for Hyperprolinemia:

Name: Hyperprolinemia 12 75 53 25 37 29 55 6 72
Proline Oxidase Deficiency 53 25
Pyrroline-5-Carboxylate Dehydrogenase Deficiency 25
Pyrroline Carboxylate Dehydrogenase Deficiency 25
Proline Dehydrogenase Deficiency 72
Proline Hydrogenase Deficiency 53
Hyperprolinemia Type 1 53
Hyperprolinemia Type 2 72
Prolinemia 25

Classifications:



External Ids:

Disease Ontology 12 DOID:0080541
KEGG 37 H00190
UMLS 72 C0268528 C0268529 C2931835

Summaries for Hyperprolinemia

Genetics Home Reference : 25 Hyperprolinemia is an excess of a particular protein building block (amino acid), called proline, in the blood. This condition generally occurs when proline is not broken down properly by the body. There are two inherited forms of hyperprolinemia, called type I and type II. People with hyperprolinemia type I often do not show any symptoms, although they have proline levels in their blood between 3 and 10 times the normal level. Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems. Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This form of the disorder has signs and symptoms that vary in severity, and is more likely than type I to involve seizures or intellectual disability. Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of lactic acid in the blood (lactic acidemia) may have hyperprolinemia as well, because lactic acid inhibits the breakdown of proline.

MalaCards based summary : Hyperprolinemia, also known as proline oxidase deficiency, is related to schizoaffective disorder and digeorge syndrome, and has symptoms including seizures An important gene associated with Hyperprolinemia is PRODH (Proline Dehydrogenase 1), and among its related pathways/superpathways are Arginine and proline metabolism and Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism. Affiliated tissues include liver, brain and cortex.

Disease Ontology : 12 An amno acid metabolic disorder that is characterized by the excess of proline in the blood.

NIH Rare Diseases : 53 Hyperprolinemia is when there is an excess of a particular protein building block (amino acid), called proline, in the blood. This condition generally occurs when proline is not broken down properly by the body. There are two inherited forms: hyperprolinemia type 1 and hyperprolinemia type 2. People with hyperprolinemia type I often do not show any symptoms, although they have proline levels in their blood between 3 and 10 times the normal level. Less commonly, affected individuals can experience seizures, intellectual disability, or other neurological or psychiatric problems. Hyperprolinemia is caused by mutations in the PRODH gene and is inherited in an autosomal recessive pattern.

KEGG : 37
Hyperprolinemia (HP) is a phenotype present in two distinct, autosomal recessive metabolic disorders caused by defects in the l-proline catabolic pathway. Hyperprolinemia type I (HPI) and type II (HPII) are caused by deficiencies in proline dehydrogenase (PRODH) and P5C dehydrogenase (P5CDH; also known as ALDH4A1), respectively. Patients with HPI may exhibit an increase in plasma proline level in absence of urinary pyrroline-5-carboxylate (P5C) while those with HPII have elevated levels of P5C and proline in plasma, urine, and cerebrospinal fluid. Some patients have neurological, renal, and/or auditory defects.

Wikipedia : 75 Hyperprolinemia is a condition which occurs when the amino acid proline is not broken down properly by... more...

Related Diseases for Hyperprolinemia

Diseases in the Hyperprolinemia family:

Hyperprolinemia, Type I Hyperprolinemia, Type Ii

Diseases related to Hyperprolinemia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 41)
# Related Disease Score Top Affiliating Genes
1 schizoaffective disorder 29.7 PRODH COMT
2 digeorge syndrome 29.4 PRODH COMT
3 velocardiofacial syndrome 29.3 PRODH COMT
4 psychotic disorder 29.2 PRODH COMT
5 bipolar disorder 29.2 PRODH COMT
6 hyperprolinemia, type ii 12.8
7 hyperprolinemia, type i 12.8
8 iminoglycinuria 10.3
9 autosomal recessive disease 10.3
10 major affective disorder 8 10.3
11 major affective disorder 9 10.3
12 schizophrenia 10.2
13 hydroxyprolinemia 10.2
14 schizophrenia 4 10.2
15 liver disease 10.2
16 aniridia 1 10.0
17 hyperglycinuria 10.0
18 telecanthus 10.0
19 craniosynostosis with fibular aplasia 10.0
20 dicarboxylic aminoaciduria 10.0
21 multiple acyl-coa dehydrogenase deficiency 10.0
22 coffin-lowry syndrome 10.0
23 branchiootic syndrome 1 10.0
24 riboflavin deficiency 10.0
25 alacrima, achalasia, and mental retardation syndrome 10.0
26 global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies 10.0
27 thalassemia 10.0
28 visual epilepsy 10.0
29 alcoholic hepatitis 10.0
30 alcoholic liver cirrhosis 10.0
31 status epilepticus 10.0
32 epilepsy 10.0
33 liver cirrhosis 10.0
34 inherited metabolic disorder 10.0
35 pyridoxine deficiency anemia 10.0
36 learning disability 10.0
37 aminoaciduria 10.0
38 childhood-onset schizophrenia 10.0
39 encephalopathy 10.0
40 seizure disorder 10.0
41 chromosomal deletion syndrome 9.6 PRODH COMT

Graphical network of the top 20 diseases related to Hyperprolinemia:



Diseases related to Hyperprolinemia

Symptoms & Phenotypes for Hyperprolinemia

UMLS symptoms related to Hyperprolinemia:


seizures

Drugs & Therapeutics for Hyperprolinemia

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Vitamin-D Treatment Targeted to Hyperprolinemia-Associated Schizophrenia. Withdrawn NCT02197286 Phase 2 Cholecalciferol;Placebo

Search NIH Clinical Center for Hyperprolinemia

Genetic Tests for Hyperprolinemia

Genetic tests related to Hyperprolinemia:

# Genetic test Affiliating Genes
1 Hyperprolinemia 29

Anatomical Context for Hyperprolinemia

MalaCards organs/tissues related to Hyperprolinemia:

41
Liver, Brain, Cortex, Skin, Testes

Publications for Hyperprolinemia

Articles related to Hyperprolinemia:

(show top 50) (show all 141)
# Title Authors PMID Year
1
Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome. 9 38
17135275 2007
2
Hyperprolinemia is not associated with childhood onset schizophrenia. 9 38
16389584 2006
3
Hyperprolinemia is a risk factor for schizoaffective disorder. 9 38
15494707 2005
4
PRODH mutations and hyperprolinemia in a subset of schizophrenic patients. 9 38
12217952 2002
5
Structural Biology of Proline Catabolic Enzymes. 38
28990412 2019
6
Proline oxidase controls proline, glutamate, and glutamine cellular concentrations in a U87 glioblastoma cell line. 38
29694413 2018
7
Structure, function, and mechanism of proline utilization A (PutA). 38
28712849 2017
8
A Genetic Analysis of the Caenorhabditis elegans Detoxification Response. 38
28428286 2017
9
Hyperprolinemia as a clue in the diagnosis of a patient with psychiatric manifestations. 38
28202261 2017
10
[Screening for amino acid metabolic disorders of newborns in Zhejiang province:prevalence, outcome and follow-up]. 38
29039163 2017
11
Selective Screening for Organic Acidurias and Amino Acidopathies in Pakistani Children. 38
28492150 2017
12
The 22q11 PRODH/DGCR6 deletion is frequent in hyperprolinemic subjects but is not a strong risk factor for ASD. 38
26978485 2016
13
Crosstalk Among Disrupted Glutamatergic and Cholinergic Homeostasis and Inflammatory Response in Mechanisms Elicited by Proline in Astrocytes. 38
25579384 2016
14
Hyperprolinemia in Type 2 Glutaric Aciduria and MADD-Like Profiles. 38
26409463 2016
15
SAXS fingerprints of aldehyde dehydrogenase oligomers. 38
26693506 2015
16
PRODH rs450046 and proline x COMT Val¹⁵⁸ Met interaction effects on intelligence and startle in adults with 22q11 deletion syndrome. 38
26068888 2015
17
Glutamatergic markers, age, intellectual functioning and psychosis in 22q11 deletion syndrome. 38
26055684 2015
18
Single amino acid polymorphism in aldehyde dehydrogenase gene superfamily. 38
25553455 2015
19
An interictal schizophrenia-like psychosis in an adult patient with 22q11.2 deletion syndrome. 38
25870791 2015
20
Hyperprolinemia induces DNA, protein and lipid damage in blood of rats: antioxidant protection. 38
24980685 2014
21
Biochemical and clinical features of hereditary hyperprolinemia. 38
24931297 2014
22
Long-term neuropsychiatric follow-up in hyperprolinemia type I. 38
24842239 2014
23
Vitamin D insufficiency and schizophrenia risk: evaluation of hyperprolinemia as a mediator of association. 38
24787057 2014
24
Long-term clinical outcome, therapy and mild mitochondrial dysfunction in hyperprolinemia. 38
24173411 2014
25
Analysis of 26 amino acids in human plasma by HPLC using AQC as derivatizing agent and its application in metabolic laboratory. 38
24515597 2014
26
Proline-induced changes in acetylcholinesterase activity and gene expression in zebrafish brain: reversal by antipsychotic drugs. 38
23867765 2013
27
Structural determinants of oligomerization of δ(1)-pyrroline-5-carboxylate dehydrogenase: identification of a hexamerization hot spot. 38
23747974 2013
28
Improving patient tolerability in immunoglobulin treatment: focus on stabilizer effects. 38
23730887 2013
29
Cytoskeleton of cortical astrocytes as a target to proline through oxidative stress mechanisms. 38
23142028 2013
30
Pyridoxine and pyridoxalphosphate-dependent epilepsies. 38
23622403 2013
31
Identification of PRODH mutations in Korean neonates with type I hyperprolinemia. 38
23462603 2013
32
Long-term proline exposure alters nucleotide catabolism and ectonucleotidase gene expression in zebrafish brain. 38
22669495 2012
33
The three-dimensional structural basis of type II hyperprolinemia. 38
22516612 2012
34
Behavioral changes induced by long-term proline exposure are reversed by antipsychotics in zebrafish. 38
22019856 2012
35
Functional specialization in proline biosynthesis of melanoma. 38
23024808 2012
36
Evidence that hyperprolinemia alters glutamatergic homeostasis in rat brain: neuroprotector effect of guanosine. 38
21935728 2012
37
Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver. 38
21882227 2012
38
Physical exercise reverses cognitive impairment in rats subjected to experimental hyperprolinemia. 38
21792675 2011
39
Evidence for association of hyperprolinemia with schizophrenia and a measure of clinical outcome. 38
21645996 2011
40
Behavioral and neurochemical effects of proline. 38
21643764 2011
41
Role of antioxidants on Na(+),K (+)-ATPase activity and gene expression in cerebral cortex of hyperprolinemic rats. 38
21509571 2011
42
Drosophila delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDh) is required for proline breakdown and mitochondrial integrity-Establishing a fly model for human type II hyperprolinemia. 38
21168532 2011
43
Type I hyperprolinemia: genotype/phenotype correlations. 38
20524212 2010
44
Proline impairs energy metabolism in cerebral cortex of young rats. 38
20437088 2010
45
Human aldehyde dehydrogenase genes: alternatively spliced transcriptional variants and their suggested nomenclature. 38
19823103 2009
46
Vitamin B6 dependent seizures. 38
19760909 2009
47
Gamma glutamyl semialdehyde dehydrogenase: simulations on native and mutant forms support the importance of outer shell lysines. 38
19000660 2009
48
Comparative aspects of tissue glutamine and proline metabolism. 38
18806120 2008
49
Effects of chronic proline administration on lipid contents of rat brain. 38
18573634 2008
50
Inborn errors of proline metabolism. 38
18806117 2008

Variations for Hyperprolinemia

ClinVar genetic disease variations for Hyperprolinemia:

6 (show top 50) (show all 71)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ALDH4A1 NM_170726.3(ALDH4A1): c.1098G> A (p.Gly366=) single nucleotide variant Conflicting interpretations of pathogenicity rs147471420 1:19203949-19203949 1:18877455-18877455
2 ALDH4A1 NM_170726.3(ALDH4A1): c.678+3G> A single nucleotide variant Conflicting interpretations of pathogenicity rs138788183 1:19209615-19209615 1:18883121-18883121
3 ALDH4A1 NM_170726.3(ALDH4A1): c.1162T> C (p.Phe388Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs41273175 1:19203725-19203725 1:18877231-18877231
4 ALDH4A1 NM_170726.3(ALDH4A1): c.1086G> C (p.Pro362=) single nucleotide variant Conflicting interpretations of pathogenicity rs41310410 1:19203961-19203961 1:18877467-18877467
5 ALDH4A1 NM_170726.3(ALDH4A1): c.1631C> T (p.Pro544Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs72953172 1:19199400-19199400 1:18872906-18872906
6 ALDH4A1 NM_170726.3(ALDH4A1): c.413C> T (p.Pro138Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs139640415 1:19212007-19212007 1:18885513-18885513
7 ALDH4A1 NM_170726.3(ALDH4A1): c.-4C> A single nucleotide variant Uncertain significance rs9426797 1:19229021-19229021 1:18902527-18902527
8 ALDH4A1 NM_170726.3(ALDH4A1): c.-7A> G single nucleotide variant Uncertain significance rs9426679 1:19229024-19229024 1:18902530-18902530
9 ALDH4A1 NM_170726.3(ALDH4A1): c.*160C> T single nucleotide variant Uncertain significance rs115664776 1:19198166-19198166 1:18871672-18871672
10 ALDH4A1 NM_170726.3(ALDH4A1): c.*186A> C single nucleotide variant Uncertain significance rs886045701 1:19198140-19198140 1:18871646-18871646
11 ALDH4A1 NM_170726.3(ALDH4A1): c.*35C> T single nucleotide variant Uncertain significance rs2230710 1:19199304-19199304 1:18872810-18872810
12 ALDH4A1 NM_170726.3(ALDH4A1): c.41+169C> A single nucleotide variant Uncertain significance rs886045705 1:19199129-19199129 1:18872635-18872635
13 ALDH4A1 NM_170726.3(ALDH4A1): c.41+182G> A single nucleotide variant Uncertain significance rs553318512 1:19199116-19199116 1:18872622-18872622
14 ALDH4A1 NM_170726.3(ALDH4A1): c.*12del deletion Uncertain significance rs774289867 1:19199327-19199327 1:18872833-18872833
15 ALDH4A1 NM_170726.3(ALDH4A1): c.41+231C> T single nucleotide variant Uncertain significance rs41273171 1:19199067-19199067 1:18872573-18872573
16 ALDH4A1 NM_170726.3(ALDH4A1): c.42-409G> A single nucleotide variant Uncertain significance rs567528405 1:19198693-19198693 1:18872199-18872199
17 ALDH4A1 NM_170726.3(ALDH4A1): c.42-365G> A single nucleotide variant Uncertain significance rs886045704 1:19198649-19198649 1:18872155-18872155
18 ALDH4A1 NM_170726.3(ALDH4A1): c.41+81T> C single nucleotide variant Uncertain significance rs2230712 1:19199217-19199217 1:18872723-18872723
19 ALDH4A1 NM_170726.3(ALDH4A1): c.41+423G> A single nucleotide variant Uncertain significance rs536186688 1:19198875-19198875 1:18872381-18872381
20 ALDH4A1 NM_170726.3(ALDH4A1): c.1073A> G (p.His358Arg) single nucleotide variant Uncertain significance rs145243354 1:19203974-19203974 1:18877480-18877480
21 ALDH4A1 NM_003748.3(ALDH4A1): c.-169dupT duplication Uncertain significance rs551988232 1:19229186-19229186 1:18902692-18902692
22 ALDH4A1 NM_003748.3(ALDH4A1): c.-65G> C single nucleotide variant Uncertain significance rs878956441 1:19229082-19229082 1:18902588-18902588
23 ALDH4A1 NM_003748.3(ALDH4A1): c.-37C> A single nucleotide variant Uncertain significance rs886045708 1:19229054-19229054 1:18902560-18902560
24 ALDH4A1 NM_170726.3(ALDH4A1): c.433G> A (p.Ala145Thr) single nucleotide variant Uncertain significance rs113846237 1:19211987-19211987 1:18885493-18885493
25 ALDH4A1 NM_170726.3(ALDH4A1): c.446T> A (p.Val149Glu) single nucleotide variant Uncertain significance rs886045706 1:19211974-19211974 1:18885480-18885480
26 ALDH4A1 NM_170726.3(ALDH4A1): c.648C> T (p.Gly216=) single nucleotide variant Uncertain significance rs139340058 1:19209648-19209648 1:18883154-18883154
27 ALDH4A1 NM_003748.3(ALDH4A1): c.-39G> T single nucleotide variant Uncertain significance rs112566606 1:19229056-19229056 1:18902562-18902562
28 ALDH4A1 NM_170726.3(ALDH4A1): c.-24G> A single nucleotide variant Uncertain significance rs886045707 1:19229041-19229041 1:18902547-18902547
29 ALDH4A1 NM_170726.3(ALDH4A1): c.490G> C (p.Ala164Pro) single nucleotide variant Uncertain significance rs369957092 1:19209886-19209886 1:18883392-18883392
30 ALDH4A1 NM_170726.3(ALDH4A1): c.800C> A (p.Pro267His) single nucleotide variant Uncertain significance rs141843191 1:19208260-19208260 1:18881766-18881766
31 ALDH4A1 NM_003748.3(ALDH4A1): c.-73C> T single nucleotide variant Uncertain significance rs559524012 1:19229090-19229090 1:18902596-18902596
32 ALDH4A1 NM_170726.3(ALDH4A1): c.584C> T (p.Thr195Met) single nucleotide variant Uncertain significance rs72936434 1:19209792-19209792 1:18883298-18883298
33 ALDH4A1 NM_170726.3(ALDH4A1): c.1369G> A (p.Val457Ile) single nucleotide variant Uncertain significance rs199828375 1:19201967-19201967 1:18875473-18875473
34 ALDH4A1 NM_170726.3(ALDH4A1): c.1261T> C (p.Cys421Arg) single nucleotide variant Uncertain significance rs149414160 1:19202886-19202886 1:18876392-18876392
35 ALDH4A1 NM_170726.3(ALDH4A1): c.1377G> C (p.Pro459=) single nucleotide variant Uncertain significance rs146222625 1:19201959-19201959 1:18875465-18875465
36 ALDH4A1 NM_170726.3(ALDH4A1): c.1082G> C (p.Trp361Ser) single nucleotide variant Uncertain significance rs763793413 1:19203965-19203965 1:18877471-18877471
37 ALDH4A1 NM_170726.3(ALDH4A1): c.1681T> A (p.Tyr561Asn) single nucleotide variant Uncertain significance rs528211463 1:19199350-19199350 1:18872856-18872856
38 ALDH4A1 NM_170726.3(ALDH4A1): c.1252G> C (p.Gly418Arg) single nucleotide variant Uncertain significance rs148586081 1:19202895-19202895 1:18876401-18876401
39 ALDH4A1 NM_170726.3(ALDH4A1): c.1381G> A (p.Asp461Asn) single nucleotide variant Uncertain significance rs377270740 1:19201955-19201955 1:18875461-18875461
40 ALDH4A1 NM_170726.3(ALDH4A1): c.421G> A (p.Ala141Thr) single nucleotide variant Uncertain significance rs377259750 1:19211999-19211999 1:18885505-18885505
41 ALDH4A1 NM_170726.3(ALDH4A1): c.135T> G (p.Pro45=) single nucleotide variant Uncertain significance rs147154947 1:19216527-19216527 1:18890033-18890033
42 ALDH4A1 NM_170726.3(ALDH4A1): c.102C> T (p.Asn34=) single nucleotide variant Uncertain significance rs148778436 1:19216560-19216560 1:18890066-18890066
43 ALDH4A1 NM_170726.3(ALDH4A1): c.-26G> T single nucleotide variant Uncertain significance rs536547354 1:19229043-19229043 1:18902549-18902549
44 ALDH4A1 NM_170726.3(ALDH4A1): c.*139G> T single nucleotide variant Uncertain significance rs886045702 1:19198187-19198187 1:18871693-18871693
45 ALDH4A1 NM_170726.3(ALDH4A1): c.42-336C> T single nucleotide variant Uncertain significance rs778905588 1:19198620-19198620 1:18872126-18872126
46 ALDH4A1 NM_170726.3(ALDH4A1): c.41+148G> A single nucleotide variant Uncertain significance rs11484737 1:19199150-19199150 1:18872656-18872656
47 ALDH4A1 NM_170726.3(ALDH4A1): c.*9C> T single nucleotide variant Uncertain significance rs138534161 1:19199330-19199330 1:18872836-18872836
48 ALDH4A1 NM_170726.3(ALDH4A1): c.*184C> G single nucleotide variant Uncertain significance rs7419135 1:19198142-19198142 1:18871648-18871648
49 ALDH4A1 NM_170726.3(ALDH4A1): c.42-111C> T single nucleotide variant Uncertain significance rs886045703 1:19198395-19198395 1:18871901-18871901
50 ALDH4A1 NM_170726.3(ALDH4A1): c.42-152C> T single nucleotide variant Uncertain significance rs148846466 1:19198436-19198436 1:18871942-18871942

Expression for Hyperprolinemia

Search GEO for disease gene expression data for Hyperprolinemia.

Pathways for Hyperprolinemia

Pathways related to Hyperprolinemia according to KEGG:

37
# Name Kegg Source Accession
1 Arginine and proline metabolism hsa00330

GO Terms for Hyperprolinemia

Biological processes related to Hyperprolinemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 proline catabolic process GO:0006562 9.26 PRODH ALDH4A1
2 4-hydroxyproline catabolic process GO:0019470 9.16 PRODH ALDH4A1
3 proline metabolic process GO:0006560 8.96 PRODH ALDH4A1
4 proline catabolic process to glutamate GO:0010133 8.62 PRODH ALDH4A1

Sources for Hyperprolinemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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