HPABH4D
MCID: HYP365
MIFTS: 26

Hyperphenylalaninemia, Bh4-Deficient, D (HPABH4D)

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

Aliases & Classifications for Hyperphenylalaninemia, Bh4-Deficient, D

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

Name: Hyperphenylalaninemia, Bh4-Deficient, D 58 76 30 13 6 41
Hyperphenylalaninemia with Primapterinuria 58 60 76 74
Cadh Deficiency 58 76
Pcbd Deficiency 58 76
Hpabh4d 58 76
Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency 58
Hyperphenylalaninemia Tetrahydrobiopterin-Deficient Due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency 76
Hyperphenylalaninemia Due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency 60
Hyperphenylalaninemia Tetrahydrobiopterin-Deficient Due to Phs Deficiency 76
Hyperphenylalaninemia Due to Dehydratase Deficiency 60
Pterin-4 Alpha-Carbinolamine Dehydratase Deficiency 60
Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency 76
Phs Deficiency 76

Characteristics:

Orphanet epidemiological data:

60
pterin-4 alpha-carbinolamine dehydratase deficiency
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
defect in tetrahydrobiopterin (bh4) synthesis
generally mild phenotype
neurologic signs are present in the neonatal period only
neurologic signs may not be present
favorable response to bh4 therapy
diabetes mellitus develops in adolescence


HPO:

33
hyperphenylalaninemia, bh4-deficient, d:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 58 264070
MeSH 45 D010661
ICD10 via Orphanet 35 E70.1
UMLS via Orphanet 75 C1849700
Orphanet 60 ORPHA1578
MedGen 43 C1849700
UMLS 74 C1849700

Summaries for Hyperphenylalaninemia, Bh4-Deficient, D

OMIM : 58 Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) D is an autosomal recessive disorder characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported (Thony et al., 1998). Patients may also develop hypomagnesemia and nonautoimmune diabetes mellitus during puberty (summary by Ferre et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of BH4-deficient hyperphenylalaninemia, see HPABH4A (261640). (264070)

MalaCards based summary : Hyperphenylalaninemia, Bh4-Deficient, D, also known as hyperphenylalaninemia with primapterinuria, is related to hyperphenylalaninemia due to dehydratase deficiency and hyperphenylalaninemia, bh4-deficient, a. An important gene associated with Hyperphenylalaninemia, Bh4-Deficient, D is PCBD1 (Pterin-4 Alpha-Carbinolamine Dehydratase 1). The drug Aminolevulinic acid has been mentioned in the context of this disorder. Related phenotypes are muscular hypotonia and tremor

UniProtKB/Swiss-Prot : 76 Hyperphenylalaninemia, BH4-deficient, D: An autosomal recessive disease characterized by primapterinuria, a variant form of hyperphenylalaninemia defined by increased excretion of 7-substituted pterins in the urine. Patients with primapterinuria show an increased ratio of neopterin to biopterin in the urine, excretion of subnormal levels of biopterins, and normal levels of biogenic amines in cerebrospinal fluid. Neurologic signs are mild, present in the neonatal period only, and include hypotonia, delayed motor development and tremor.

Related Diseases for Hyperphenylalaninemia, Bh4-Deficient, D

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

Hyperphenylalaninemia, Bh4-Deficient, C Hyperphenylalaninemia, Bh4-Deficient, a
Hyperphenylalaninemia, Bh4-Deficient, D

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

# Related Disease Score Top Affiliating Genes
1 hyperphenylalaninemia due to dehydratase deficiency 11.5
2 hyperphenylalaninemia, bh4-deficient, a 11.2

Symptoms & Phenotypes for Hyperphenylalaninemia, Bh4-Deficient, D

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

33 (show all 7)
# Description HPO Frequency HPO Source Accession
1 muscular hypotonia 33 HP:0001252
2 tremor 33 HP:0001337
3 hypertonia 33 HP:0001276
4 motor delay 33 HP:0001270
5 generalized hypotonia 33 HP:0001290
6 hyperphenylalaninemia 33 HP:0004923
7 transient hyperphenylalaninemia 33 HP:0008297

Symptoms via clinical synopsis from OMIM:

58
Laboratory Abnormalities:
hyperphenylalaninemia
increased urinary 7-biopterin (primapterin)
increased urinary neopterin
low serum magnesium
increased urinary magnesium
more
Neurologic Central Nervous System:
hypotonia, mild, transient
hypertonia, mild, transient
delayed motor development, mild, transient
tremor, mild, transient endocrine : nonautoimmune diabetes mellitus, juvenile-onset

Clinical features from OMIM:

264070

Drugs & Therapeutics for Hyperphenylalaninemia, Bh4-Deficient, D

Drugs for Hyperphenylalaninemia, Bh4-Deficient, D (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Aminolevulinic acid Approved 106-60-5 137

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Longitudinal Study of the Porphyrias Recruiting NCT01561157

Search NIH Clinical Center for Hyperphenylalaninemia, Bh4-Deficient, D

Genetic Tests for Hyperphenylalaninemia, Bh4-Deficient, D

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

# Genetic test Affiliating Genes
1 Hyperphenylalaninemia, Bh4-Deficient, D 30 PCBD1

Anatomical Context for Hyperphenylalaninemia, Bh4-Deficient, D

Publications for Hyperphenylalaninemia, Bh4-Deficient, D

Articles related to Hyperphenylalaninemia, Bh4-Deficient, D:

# Title Authors Year
1
Recessive mutations in PCBD1 cause a new type of early-onset diabetes. ( 24848070 )
2014
2
Hyperphenylalaninemia with high levels of 7-biopterin is associated with mutations in the PCBD gene encoding the bifunctional protein pterin-4a-carbinolamine dehydratase and transcriptional coactivator (DCoH). ( 9585615 )
1998
3
Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a benign form of hyperphenylalaninemia. ( 9760199 )
1998
4
Characterization of the wild-type form of 4a-carbinolamine dehydratase and two naturally occurring mutants associated with hyperphenylalaninemia. ( 8618906 )
1995
5
Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism. ( 8352282 )
1993

Variations for Hyperphenylalaninemia, Bh4-Deficient, D

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

76
# Symbol AA change Variation ID SNP ID
1 PCBD1 p.Cys82Arg VAR_005528 rs104894177
2 PCBD1 p.Arg88Gln VAR_005529 rs115117837
3 PCBD1 p.Glu97Lys VAR_005530 rs397518416

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

6 (show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 PCBD1 NM_000281.3(PCBD1): c.259G> T (p.Glu87Ter) single nucleotide variant Pathogenic rs104894172 GRCh37 Chromosome 10, 72643763: 72643763
2 PCBD1 NM_000281.3(PCBD1): c.259G> T (p.Glu87Ter) single nucleotide variant Pathogenic rs104894172 GRCh38 Chromosome 10, 70884006: 70884006
3 PCBD1 NM_000281.3(PCBD1): c.244T> C (p.Cys82Arg) single nucleotide variant Pathogenic rs104894177 GRCh37 Chromosome 10, 72643778: 72643778
4 PCBD1 NM_000281.3(PCBD1): c.244T> C (p.Cys82Arg) single nucleotide variant Pathogenic rs104894177 GRCh38 Chromosome 10, 70884021: 70884021
5 PCBD1 NM_000281.3(PCBD1): c.236C> T (p.Thr79Ile) single nucleotide variant Pathogenic rs121913014 GRCh37 Chromosome 10, 72643786: 72643786
6 PCBD1 NM_000281.3(PCBD1): c.236C> T (p.Thr79Ile) single nucleotide variant Pathogenic rs121913014 GRCh38 Chromosome 10, 70884029: 70884029
7 PCBD1 NM_000281.3(PCBD1): c.292C> T (p.Gln98Ter) single nucleotide variant Pathogenic rs121913015 GRCh37 Chromosome 10, 72643730: 72643730
8 PCBD1 NM_000281.3(PCBD1): c.292C> T (p.Gln98Ter) single nucleotide variant Pathogenic rs121913015 GRCh38 Chromosome 10, 70883973: 70883973
9 PCBD1 NM_000281.3(PCBD1): c.213_215del (p.Asn71del) deletion not provided rs397518415 GRCh37 Chromosome 10, 72644910: 72644912
10 PCBD1 NM_000281.3(PCBD1): c.213_215del (p.Asn71del) deletion not provided rs397518415 GRCh38 Chromosome 10, 70885153: 70885155
11 PCBD1 NM_000281.3(PCBD1): c.289G> A (p.Glu97Lys) single nucleotide variant not provided rs397518416 GRCh37 Chromosome 10, 72643733: 72643733
12 PCBD1 NM_000281.3(PCBD1): c.289G> A (p.Glu97Lys) single nucleotide variant not provided rs397518416 GRCh38 Chromosome 10, 70883976: 70883976
13 PCBD1 NM_000281.4(PCBD1): c.263G> A (p.Arg88Gln) single nucleotide variant no interpretation for the single variant rs115117837 GRCh37 Chromosome 10, 72643759: 72643759
14 PCBD1 NM_000281.4(PCBD1): c.263G> A (p.Arg88Gln) single nucleotide variant no interpretation for the single variant rs115117837 GRCh38 Chromosome 10, 70884002: 70884002
15 PCBD1 NM_000281.4(PCBD1): c.79G> T (p.Glu27Ter) single nucleotide variant no interpretation for the single variant rs727505360 GRCh37 Chromosome 10, 72645611: 72645611
16 PCBD1 NM_000281.4(PCBD1): c.79G> T (p.Glu27Ter) single nucleotide variant no interpretation for the single variant rs727505360 GRCh38 Chromosome 10, 70885854: 70885854
17 PCBD1 NM_000281.3(PCBD1): c.205G> A (p.Val69Met) single nucleotide variant Uncertain significance rs200188190 GRCh38 Chromosome 10, 70885163: 70885163
18 PCBD1 NM_000281.3(PCBD1): c.205G> A (p.Val69Met) single nucleotide variant Uncertain significance rs200188190 GRCh37 Chromosome 10, 72644920: 72644920
19 PCBD1 NM_000281.3(PCBD1): c.313T> C (p.Ter105Gln) single nucleotide variant Pathogenic rs770334825 GRCh37 Chromosome 10, 72643709: 72643709
20 PCBD1 NM_000281.3(PCBD1): c.313T> C (p.Ter105Gln) single nucleotide variant Pathogenic rs770334825 GRCh38 Chromosome 10, 70883952: 70883952
21 PCBD1 NM_000281.3(PCBD1): c.179T> C (p.Leu60Pro) single nucleotide variant Uncertain significance rs768330993 GRCh37 Chromosome 10, 72644946: 72644946
22 PCBD1 NM_000281.3(PCBD1): c.179T> C (p.Leu60Pro) single nucleotide variant Uncertain significance rs768330993 GRCh38 Chromosome 10, 70885189: 70885189

Expression for Hyperphenylalaninemia, Bh4-Deficient, D

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

Pathways for Hyperphenylalaninemia, Bh4-Deficient, D

GO Terms for Hyperphenylalaninemia, Bh4-Deficient, D

Sources for Hyperphenylalaninemia, Bh4-Deficient, D

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