MCID: CLS049
MIFTS: 41

Classic Phenylketonuria

Categories: Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Classic Phenylketonuria

MalaCards integrated aliases for Classic Phenylketonuria:

Name: Classic Phenylketonuria 58 6
Classical Phenylketonuria 71 32
Phenylketonuria Classical 54
Classic Pku 58

Characteristics:

Orphanet epidemiological data:

58
classic phenylketonuria
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Classic Phenylketonuria

MalaCards based summary : Classic Phenylketonuria, also known as classical phenylketonuria, is related to phenylketonuria and hyperphenylalaninemia, bh4-deficient, a, and has symptoms including dry skin An important gene associated with Classic Phenylketonuria is PAH (Phenylalanine Hydroxylase), and among its related pathways/superpathways are Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism and Folate biosynthesis. Affiliated tissues include cortex and hypothalamus, and related phenotypes are global developmental delay and intellectual disability, severe

Related Diseases for Classic Phenylketonuria

Graphical network of the top 20 diseases related to Classic Phenylketonuria:



Diseases related to Classic Phenylketonuria

Symptoms & Phenotypes for Classic Phenylketonuria

Human phenotypes related to Classic Phenylketonuria:

58 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
2 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
3 growth delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001510
4 hypopigmentation of hair 58 31 hallmark (90%) Very frequent (99-80%) HP:0005599
5 hypopigmentation of the skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0001010
6 hyperphenylalaninemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0004923
7 nausea and vomiting 58 31 frequent (33%) Frequent (79-30%) HP:0002017
8 depressivity 58 31 frequent (33%) Frequent (79-30%) HP:0000716
9 tremor 58 31 frequent (33%) Frequent (79-30%) HP:0001337
10 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
11 hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0001276
12 autism 58 31 frequent (33%) Frequent (79-30%) HP:0000717
13 attention deficit hyperactivity disorder 58 31 frequent (33%) Frequent (79-30%) HP:0007018
14 eczema 58 31 frequent (33%) Frequent (79-30%) HP:0000964
15 memory impairment 58 31 frequent (33%) Frequent (79-30%) HP:0002354
16 seizure 31 frequent (33%) HP:0001250
17 hyperreflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001347
18 cerebral calcification 58 31 occasional (7.5%) Occasional (29-5%) HP:0002514
19 self-injurious behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0100716
20 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
21 motor deterioration 58 31 occasional (7.5%) Occasional (29-5%) HP:0002333
22 lack of skin elasticity 58 31 occasional (7.5%) Occasional (29-5%) HP:0100679
23 paraplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0010550
24 hemiplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002301
25 seizures 58 Frequent (79-30%)
26 behavioral abnormality 58 Very frequent (99-80%)
27 mental deterioration 58 Frequent (79-30%)

UMLS symptoms related to Classic Phenylketonuria:


dry skin

Drugs & Therapeutics for Classic Phenylketonuria

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Nutrition Status of Adult and Adolescent Patients With Classical Phenylketonuria (PKU) and Hyperphenylalaninemia Completed NCT01879995
2 The Effects of Sapropterin Dihydrochloride Supplementation on in Vivo Redox Status in Patients With Classical Phenylketonuria Withdrawn NCT01650909

Search NIH Clinical Center for Classic Phenylketonuria

Genetic Tests for Classic Phenylketonuria

Anatomical Context for Classic Phenylketonuria

MalaCards organs/tissues related to Classic Phenylketonuria:

40
Cortex, Hypothalamus

Publications for Classic Phenylketonuria

Articles related to Classic Phenylketonuria:

(show top 50) (show all 361)
# Title Authors PMID Year
1
Identification of three novel PKU mutations among Chinese: evidence for recombination or recurrent mutation at the PAH locus. 54 61 6
1349576 1992
2
Aberrant splicing of phenylalanine hydroxylase mRNA: the major cause for phenylketonuria in parts of southern Europe. 6 61 54
1769645 1991
3
Mutation detection in phenylketonuria by using chemical cleavage of mismatch: importance of using probes from both normal and patient samples. 61 6 54
2063869 1991
4
Identification of a novel phenylketonuria (PKU) mutation in the Chinese: further evidence for multiple origins of PKU in Asia. 61 54 6
1998345 1991
5
Two distinct mutations at a single BamHI site in phenylketonuria. 6 54 61
1671881 1991
6
Time and space clusters of the French-Canadian M1V phenylketonuria mutation in France. 61 6
1609797 1992
7
In vitro and in vivo correlations for I65T and M1V mutations at the phenylalanine hydroxylase locus. 61 6
1301201 1992
8
Founder effect of a prevalent phenylketonuria mutation in the Oriental population. 61 6
2006152 1991
9
Two mutations within the coding sequence of the phenylalanine hydroxylase gene. 6 61
1975559 1990
10
GT to AT transition at a splice donor site causes skipping of the preceding exon in phenylketonuria. 6 61
3615198 1987
11
A comprehensive study of phenylalanine hydroxylase gene mutations in the Iranian phenylketonuria patients. 6
30389586 2019
12
[Mutational spectrum of phenylalanine hydroxylase gene and identification of novel mutations in patients with hyperphenylalaninemia in Jiangsu province]. 6
24078561 2013
13
Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability. 6
18538294 2008
14
Phenylalanine hydroxylase deficiency exhibits mutation heterogeneity in two large old order Amish settlements. 6
17630668 2007
15
Molecular and phenotypic characteristics of patients with phenylketonuria in Serbia and Montenegro. 6
16879198 2006
16
Genetic diversity within the R408W phenylketonuria mutation lineages in Europe. 6
12655548 2003
17
A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria. 6
11214902 2001
18
Large heterozygous deletion masquerading as homozygous missense mutation: a pitfall in diagnostic mutation analysis. 6
10472529 1999
19
Maternal phenylketonuria in two Sicilian families identified by maternal blood phenylalanine level screening and identification of a new phenylalanine hydroxylase gene mutation (P407L) 6
9950317 1999
20
A molecular survey of phenylketonuria in Iceland: identification of a founding mutation and evidence of predominant Norse settlement. 6
9450182 1997
21
Prediction of multiple hypermutable codons in the human PAH gene: codon 280 contains recurrent mutations in Quebec and other populations. 6
9101291 1997
22
Phenylketonuria in Spanish Gypsies: prevalence of the IVS10nt546 mutation on haplotype 34. 6
8990013 1997
23
PKU mutation G46S is associated with increased aggregation and degradation of the phenylalanine hydroxylase enzyme. 6
8829656 1996
24
Evidence in Latin America of recurrence of V388M, a phenylketonuria mutation with high in vitro residual activity. 6
7668259 1995
25
The PKU mutation S349P causes complete loss of catalytic activity in the recombinant phenylalanine hydroxylase enzyme. 6
7860062 1995
26
Mutation analysis of phenylketonuria in south and central Portugal: prevalence of V388M mutation. 6
7581408 1995
27
Gypsy phenylketonuria: a point mutation of the phenylalanine hydroxylase gene in Gypsy families from Slovakia. 6
8116675 1994
28
Geographical distribution of the P281L mutation at the phenylalanine hydroxylase locus: possible origin in southeastern Europe. 6
7807961 1994
29
The phenylketonuria G272X haplotype 7 mutation in European populations. 6
8370573 1993
30
Presence of the Mediterranean PKU mutation IVS10 in Latin America. 6
8401510 1993
31
Phenylketonuria: variable phenotypic outcomes of the R261Q mutation and maternal PKU in the offspring of a healthy homozygote. 6
8487271 1993
32
Molecular analysis of contiguous exons of the phenylalanine hydroxylase gene: identification of a new PKU mutation. 6
8097261 1993
33
Rapid and efficient PCR/StyI test for identification of common mutation R408W in phenylketonuria patients. 6
8445621 1993
34
A missense mutation, S349P, completely inactivates phenylalanine hydroxylase in north African Jews with phenylketonuria. 6
8095248 1993
35
Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria. 6
8098245 1993
36
Novel phenylketonuria mutation detected by analysis of ectopically transcribed phenylalanine hydroxylase mRNA from lymphoblast. 6
1360590 1992
37
A new 15 bp deletion in exon 11 of the phenylalanine hydroxylase gene in phenylketonuria. 6
1363837 1992
38
A new PKU mutation associated with haplotype 12. 6
1363838 1992
39
Identification of a missense phenylketonuria mutation at codon 408 in Chinese. 6
1355066 1992
40
Mutation analysis of phenylketonuria in Spain: prevalence of two Mediterranean mutations. 6
1601425 1992
41
PKU mutations R408Q and F299C in Norway: haplotype associations, geographic distributions and phenotype characteristics. 6
1312992 1992
42
Five mutations at the PAH locus account for almost 90% of PKU mutations in French-Canadians from eastern Quebec. 6
1301193 1992
43
A de novo phenylketonuria mutation: ATG (Met) to ATA (Ile) in the start codon of the phenylalanine hydroxylase gene. 6
1301947 1992
44
Illegitimate transcription of phenylalanine hydroxylase for detection of mutations in patients with phenylketonuria. 6
1301202 1992
45
Silent mutations in the phenylalanine hydroxylase gene as an aid to the diagnosis of phenylketonuria. 6
1682495 1991
46
A frameshift mutation in exon 2 of the phenylalanine hydroxylase gene linked to RFLP haplotype 1. 6
1682235 1991
47
The identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria. 6
1679030 1991
48
Single-strand conformation polymorphism for detection of mutations and base substitutions in phenylketonuria. 6
2035532 1991
49
Missense mutations prevalent in Orientals with phenylketonuria: molecular characterization and clinical implications. 6
2071149 1991
50
A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria. 6
1709636 1991

Variations for Classic Phenylketonuria

ClinVar genetic disease variations for Classic Phenylketonuria:

6 (show top 50) (show all 741)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PAH NM_000277.3(PAH):c.977G>A (p.Trp326Ter) SNV Pathogenic 579 rs62514959 12:103238202-103238202 12:102844424-102844424
2 PAH PAH, SER349ARG Variation Pathogenic 606
3 PAH NM_000277.3(PAH):c.842+2T>A SNV Pathogenic 614 rs62514955 12:103246591-103246591 12:102852813-102852813
4 PAH NM_000277.3(PAH):c.1092_1106del (p.Leu365_Leu369del) Deletion Pathogenic 620 rs62516097 12:103237517-103237531 12:102843739-102843753
5 PAH NM_000277.3(PAH):c.1076C>G (p.Ser359Ter) SNV Pathogenic 626 rs5030854 12:103237547-103237547 12:102843769-102843769
6 PAH NM_000277.3(PAH):c.136G>A (p.Gly46Ser) SNV Pathogenic 629 rs74603784 12:103306601-103306601 12:102912823-102912823
7 PAH NM_000277.3(PAH):c.1129del (p.Tyr377fs) Deletion Pathogenic 634 rs62642941 12:103237494-103237494 12:102843716-102843716
8 PAH NM_000277.3(PAH):c.1220C>T (p.Pro407Leu) SNV Pathogenic 635 rs62644473 12:103234273-103234273 12:102840495-102840495
9 PAH NM_000277.1(PAH):c.913_1199del (p.Ile306Leufs) Deletion Pathogenic 637 12:102840516-102851686
10 PAH NM_000277.3(PAH):c.3G>A (p.Met1Ile) SNV Pathogenic 622 rs62514893 12:103310906-103310906 12:102917128-102917128
11 PAH NM_000277.3(PAH):c.1066-2A>T SNV Pathogenic 120258 rs281865447 12:103237559-103237559 12:102843781-102843781
12 PAH NM_000277.3(PAH):c.169G>T (p.Glu57Ter) SNV Pathogenic 120268 rs140945592 12:103288696-103288696 12:102894918-102894918
13 PAH NM_000277.3(PAH):c.196G>T (p.Glu66Ter) SNV Pathogenic 120270 rs281865454 12:103288669-103288669 12:102894891-102894891
14 PAH NM_000277.3(PAH):c.350del (p.Thr117fs) Deletion Pathogenic 120274 rs281865428 12:103288515-103288515 12:102894737-102894737
15 PAH NM_000277.3(PAH):c.442-2A>C SNV Pathogenic 120276 rs281865448 12:103260443-103260443 12:102866665-102866665
16 PAH NM_000277.3(PAH):c.837del (p.Glu280fs) Deletion Pathogenic 120288 rs281865429 12:103246598-103246598 12:102852820-102852820
17 PAH NM_000277.3(PAH):c.912+2T>C SNV Pathogenic 120292 rs281865449 12:103245463-103245463 12:102851685-102851685
18 PAH NM_000277.3(PAH):c.916del (p.Ile306fs) Deletion Pathogenic 120296 rs281865456 12:103240726-103240726 12:102846948-102846948
19 PAH NM_000277.3(PAH):c.927_928CT[2] (p.Leu311fs) Microsatellite Pathogenic 120297 rs281865430 12:103240710-103240711 12:102846932-102846933
20 PAH NM_000277.3(PAH):c.155del (p.Leu52fs) Deletion Pathogenic 120310 rs281865165 12:103306582-103306582 12:102912804-102912804
21 PAH NM_000277.3(PAH):c.847A>T (p.Ile283Phe) SNV Pathogenic 102876 rs62517168 12:103245530-103245530 12:102851752-102851752
22 PAH NM_000277.3(PAH):c.168+1G>A SNV Pathogenic 102604 rs62514898 12:103306568-103306568 12:102912790-102912790
23 PAH NM_000277.3(PAH):c.578_579CT[1] (p.Leu194fs) Microsatellite Pathogenic 102741 rs62508587 12:103249039-103249040 12:102855261-102855262
24 PAH NM_000277.3(PAH):c.694C>T (p.Gln232Ter) SNV Pathogenic 102788 rs62507348 12:103248926-103248926 12:102855148-102855148
25 PAH NM_000277.3(PAH):c.357del (p.Trp120fs) Deletion Pathogenic 197125 rs794727619 12:103271324-103271324 12:102877546-102877546
26 PAH NM_000277.3(PAH):c.648C>G (p.Tyr216Ter) SNV Pathogenic 102769 rs62509013 12:103248972-103248972 12:102855194-102855194
27 PAH NM_000277.3(PAH):c.168+5G>C SNV Pathogenic 102606 rs62507288 12:103306564-103306564 12:102912786-102912786
28 PAH NM_000277.3(PAH):c.1147C>T (p.Gln383Ter) SNV Pathogenic 370701 rs1037293795 12:103237476-103237476 12:102843698-102843698
29 PAH NM_000277.3(PAH):c.975C>G (p.Tyr325Ter) SNV Pathogenic 102921 rs62508573 12:103238204-103238204 12:102844426-102844426
30 PAH NM_000277.3(PAH):c.1065+1G>A SNV Pathogenic 102501 rs62516147 12:103238113-103238113 12:102844335-102844335
31 PAH NM_000277.3(PAH):c.1024del (p.Ala342fs) Deletion Pathogenic 102475 rs63581460 12:103238155-103238155 12:102844377-102844377
32 PAH NM_000277.3(PAH):c.558_559del (p.Trp187fs) Deletion Pathogenic 102734 rs62517207 12:103249061-103249062 12:102855283-102855284
33 PAH NM_000277.3(PAH):c.782G>C (p.Arg261Pro) SNV Pathogenic 102832 rs5030849 12:103246653-103246653 12:102852875-102852875
34 PAH NM_000277.3(PAH):c.498C>G (p.Tyr166Ter) SNV Pathogenic 371373 rs199475645 12:103260385-103260385 12:102866607-102866607
35 PAH NM_000277.3(PAH):c.398_401del (p.Asn133fs) Deletion Pathogenic 102663 rs199475605 12:103271280-103271283 12:102877502-102877505
36 PAH NC_000012.11:g.(?_103248894)_(103249130_?)del Deletion Pathogenic 458077 12:103248894-103249130
37 PAH NM_000277.3(PAH):c.737del (p.Ala246fs) Deletion Pathogenic 102814 rs199475666 12:103246698-103246698 12:102852920-102852920
38 PAH NM_000277.3(PAH):c.865G>A (p.Gly289Arg) SNV Pathogenic 458082 rs199475693 12:103245512-103245512 12:102851734-102851734
39 PAH NM_000277.3(PAH):c.553_706+647del Deletion Pathogenic 458079 12:103248267-103249067 12:102854489-102855289
40 PAH NM_000277.3(PAH):c.618C>G (p.Tyr206Ter) SNV Pathogenic 102763 rs62517201 12:103249002-103249002 12:102855224-102855224
41 PAH NM_000277.3(PAH):c.556del (p.Thr186fs) Deletion Pathogenic 102733 rs62507328 12:103249064-103249064 12:102855286-102855286
42 PAH NM_000277.3(PAH):c.592_613del (p.Tyr198fs) Deletion Pathogenic 102746 rs199475697 12:103249007-103249028 12:102855229-102855250
43 PAH NM_000277.3(PAH):c.839A>G (p.Glu280Gly) SNV Pathogenic 102866 rs62508734 12:103246596-103246596 12:102852818-102852818
44 PAH NM_000277.3(PAH):c.569T>C (p.Val190Ala) SNV Pathogenic 102740 rs62514919 12:103249051-103249051 12:102855273-102855273
45 PAH NM_000277.3(PAH):c.734T>A (p.Val245Glu) SNV Pathogenic 102811 rs76212747 12:103246701-103246701 12:102852923-102852923
46 PAH NM_000277.3(PAH):c.1340C>A (p.Ala447Asp) SNV Pathogenic 102595 rs76542238 12:103232972-103232972 12:102839194-102839194
47 PAH NM_000277.3(PAH):c.1199+1G>A SNV Pathogenic 102556 rs62509015 12:103237423-103237423 12:102843645-102843645
48 PAH NM_000277.3(PAH):c.707-12_711del Deletion Pathogenic 527863 rs1555204492 12:103246724-103246740 12:102852946-102852962
49 PAH NC_000012.12:g.(?_102854491)_(102855289_?)del Deletion Pathogenic 527864 12:103248269-103249067 12:102854491-102855289
50 PAH NC_000012.12:g.(?_102866576)_(102866683_?)del Deletion Pathogenic 527865 12:103260354-103260461 12:102866576-102866683

Expression for Classic Phenylketonuria

Search GEO for disease gene expression data for Classic Phenylketonuria.

Pathways for Classic Phenylketonuria

GO Terms for Classic Phenylketonuria

Biological processes related to Classic Phenylketonuria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular amino acid metabolic process GO:0006520 9.16 QDPR PTS
2 L-phenylalanine catabolic process GO:0006559 8.96 QDPR PAH
3 tetrahydrobiopterin biosynthetic process GO:0006729 8.62 QDPR PTS

Sources for Classic Phenylketonuria

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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....