MCID: HYP368
MIFTS: 30

Hyperphenylalaninemia, Bh4-Deficient, C

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases

Aliases & Classifications for Hyperphenylalaninemia, Bh4-Deficient, C

MalaCards integrated aliases for Hyperphenylalaninemia, Bh4-Deficient, C:

Name: Hyperphenylalaninemia, Bh4-Deficient, C 54 71 13
Dihydropteridine Reductase Deficiency 50 24 56 71 29
Quinoid Dihydropteridine Reductase Deficiency 50 24 71
Dhpr Deficiency 50 24 71
Qdpr Deficiency 50 24 71
Hyperphenylalaninemia Due to Dihydropteridine Reductase Deficiency 50 56
Phenylketonuria Type 2 50 56
Pku Type 2 50 56
Hpabh4c 24 71
Hyperphenylalaninemia Tetrahydrobiopterin-Deficient Due to Dhpr Deficiency 71
Hyperphenylalaninemia, Bh-4-Deficient, C 50
Bh4-Deficient Hyperphenylalaninemia C 24
Quinoid Dihydropteridine Reductase 13
Phenylketonuria Ii 69

Characteristics:

Orphanet epidemiological data:

56
dihydropteridine reductase deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
variable severity
defect in tetrahydrobiopterin (bh4) synthesis
treatment with bh4 is effective
neurotransmitter treatment with l-dopa and serotonin or precursors is effective
early treatment can reduce neurologic symptoms
progressive neurologic deterioration if untreated
diurnal fluctuation of neurologic symptoms


HPO:

32
hyperphenylalaninemia, bh4-deficient, c:
Onset and clinical course variable expressivity infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hyperphenylalaninemia, Bh4-Deficient, C

NIH Rare Diseases : 50 dihydropteridine reductase deficiency (dhpr) is a severe form of hyperphenylalaninemia (high levels of the amino acidphenylalanine in the blood) due to impaired renewal of a substance known as tetrahydrobiopterin (bh4). tetrahydrobiopterin normally helps process several amino acids, including phenylalanine, and it is also involved in the production of neurotransmitters. if little or no tetrahydrobiopterin is available to help process phenylalanine, this amino acid can build up in the blood and other tissues and the levels of neurotransmitters (dopamine, serotonin) and folate in cerebrospinal fluid are also decreased. this results in neurological symptoms such as psychomotor delay, low muscle tone (hypotonia), seizures, abnormal movements, too much salivation, and swallowing difficulties. dhpr deficiency is caused by mutations in the qdpr gene. it is inherited in an autosomal recessive manner. treatment should be started as soon as possible and includes bh4 supplementation usually combined with a diet without phenylalanine, folate supplementation, and specific medications to restore the levels of neurotransmitters in the brain. last updated: 12/28/2015

MalaCards based summary : Hyperphenylalaninemia, Bh4-Deficient, C, also known as dihydropteridine reductase deficiency, is related to hyperphenylalaninemia, bh4-deficient, a and hyperphenylalaninemia, and has symptoms including dysphagia, microcephaly and global developmental delay. An important gene associated with Hyperphenylalaninemia, Bh4-Deficient, C is QDPR (Quinoid Dihydropteridine Reductase). Affiliated tissues include brain.

UniProtKB/Swiss-Prot : 71 Hyperphenylalaninemia, BH4-deficient, C: Rare autosomal recessive disorder characterized by hyperphenylalaninemia and severe neurologic symptoms (malignant hyperphenylalaninemia) including axial hypotonia and truncal hypertonia, abnormal thermogenesis, and microcephaly. These signs are attributable to depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases that use BH-4 as cofactor. Patients do not respond to phenylalanine-restricted diet. HPABH4C is lethal if untreated.

Description from OMIM: 261630

Related Diseases for Hyperphenylalaninemia, Bh4-Deficient, C

Diseases in the Hyperphenylalaninemia, Bh4-Deficient, C family:

Hyperphenylalaninemia, Bh4-Deficient, D Hyperphenylalaninemia, Bh4-Deficient, a
Hyperphenylalaninemia, Bh4-Deficient, B

Diseases related to Hyperphenylalaninemia, Bh4-Deficient, C via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 hyperphenylalaninemia, bh4-deficient, a 10.8
2 hyperphenylalaninemia 10.3
3 phenylketonuria 10.2
4 neuroblastoma 9.9
5 leukemia 9.9
6 lymphoblastic leukemia 9.9
7 mild hyperphenylalaninemia 9.9

Graphical network of the top 20 diseases related to Hyperphenylalaninemia, Bh4-Deficient, C:



Diseases related to Hyperphenylalaninemia, Bh4-Deficient, C

Symptoms & Phenotypes for Hyperphenylalaninemia, Bh4-Deficient, C

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
mental retardation
dystonia
tremor
choreoathetosis
seizures
more
Neurologic- Behavioral Psychiatric Manifestations:
irritability

Growth- Other:
poor feeding in infancy

Metabolic Features:
hyperthermia, episodic

Head And Neck- Head:
microcephaly

Abdomen- Gastroin testinal:
swallowing difficulties

Head And Neck- Mouth:
hypersalivation

Laboratory- Abnormalities:
hyperphenylalaninemia
decreased homovanillic acid (hva) and 5-hydroxyindoleacetic acid (5hiaa) in csf
increased biopterin in urine and csf
decreased or absent dihydropteridine reductase activity


Clinical features from OMIM:

261630

Human phenotypes related to Hyperphenylalaninemia, Bh4-Deficient, C:

56 32 (show all 17)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphagia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002015
2 microcephaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0000252
3 global developmental delay 56 32 hallmark (90%) Very frequent (99-80%) HP:0001263
4 intellectual disability 56 32 hallmark (90%) Very frequent (99-80%) HP:0001249
5 dystonia 32 HP:0001332
6 myoclonus 32 HP:0001336
7 tremor 32 HP:0001337
8 choreoathetosis 32 HP:0001266
9 seizures 32 HP:0001250
10 hypertonia 32 HP:0001276
11 irritability 32 HP:0000737
12 progressive neurologic deterioration 32 HP:0002344
13 muscular hypotonia 32 HP:0001252
14 hyperphenylalaninemia 32 HP:0004923
15 cerebral calcification 32 HP:0002514
16 episodic fever 32 HP:0001954
17 excessive salivation 32 HP:0003781

UMLS symptoms related to Hyperphenylalaninemia, Bh4-Deficient, C:


seizures, tremor

Drugs & Therapeutics for Hyperphenylalaninemia, Bh4-Deficient, C

Search Clinical Trials , NIH Clinical Center for Hyperphenylalaninemia, Bh4-Deficient, C

Genetic Tests for Hyperphenylalaninemia, Bh4-Deficient, C

Genetic tests related to Hyperphenylalaninemia, Bh4-Deficient, C:

id Genetic test Affiliating Genes
1 Dihydropteridine Reductase Deficiency 29
2 Bh4-Deficient Hyperphenylalaninemia C 24 QDPR

Anatomical Context for Hyperphenylalaninemia, Bh4-Deficient, C

MalaCards organs/tissues related to Hyperphenylalaninemia, Bh4-Deficient, C:

39
Brain

Publications for Hyperphenylalaninemia, Bh4-Deficient, C

Variations for Hyperphenylalaninemia, Bh4-Deficient, C

UniProtKB/Swiss-Prot genetic disease variations for Hyperphenylalaninemia, Bh4-Deficient, C:

71 (show all 16)
id Symbol AA change Variation ID SNP ID
1 QDPR p.Gly23Asp VAR_006960 rs104893863
2 QDPR p.Trp36Arg VAR_006961 rs104893865
3 QDPR p.Leu74Pro VAR_006962
4 QDPR p.Trp108Gly VAR_006963 rs104893864
5 QDPR p.Pro145Leu VAR_006965
6 QDPR p.Tyr150Cys VAR_006966 rs104893866
7 QDPR p.Gly151Ser VAR_006967
8 QDPR p.His158Tyr VAR_006968 rs750201480
9 QDPR p.Gly170Ser VAR_006969 rs769460415
10 QDPR p.Phe212Cys VAR_006970
11 QDPR p.Leu14Pro VAR_008121 rs756639609
12 QDPR p.Gly17Val VAR_008122
13 QDPR p.Gly17Arg VAR_021767 rs757483045
14 QDPR p.Gly18Asp VAR_021768
15 QDPR p.Gln66Arg VAR_021769
16 QDPR p.Gly149Arg VAR_021770

ClinVar genetic disease variations for Hyperphenylalaninemia, Bh4-Deficient, C:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 QDPR QDPR, 3-BP INS, 390ACT insertion Pathogenic
2 QDPR NM_000320.2(QDPR): c.68G> A (p.Gly23Asp) single nucleotide variant Pathogenic rs104893863 GRCh37 Chromosome 4, 17513610: 17513610
3 QDPR NM_000320.2(QDPR): c.322T> G (p.Trp108Gly) single nucleotide variant Pathogenic rs104893864 GRCh37 Chromosome 4, 17503456: 17503456
4 QDPR NM_000320.2(QDPR): c.106T> C (p.Trp36Arg) single nucleotide variant Pathogenic rs104893865 GRCh37 Chromosome 4, 17510986: 17510986
5 QDPR QDPR, IVS3, A-G, 152-BP INS insertion Pathogenic
6 QDPR NM_000320.2(QDPR): c.449A> G (p.Tyr150Cys) single nucleotide variant Pathogenic rs104893866 GRCh37 Chromosome 4, 17493951: 17493951
7 QDPR NM_000320.2(QDPR): c.270G> A (p.Trp90Ter) single nucleotide variant Pathogenic rs104893867 GRCh37 Chromosome 4, 17506027: 17506027

Expression for Hyperphenylalaninemia, Bh4-Deficient, C

Search GEO for disease gene expression data for Hyperphenylalaninemia, Bh4-Deficient, C.

Pathways for Hyperphenylalaninemia, Bh4-Deficient, C

GO Terms for Hyperphenylalaninemia, Bh4-Deficient, C

Sources for Hyperphenylalaninemia, Bh4-Deficient, C

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70 UMLS via Orphanet
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