HPABH4D
MCID: HYP365
MIFTS: 31

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 56 52 73 29 13 6
Hyperphenylalaninemia with Primapterinuria 56 52 58 73 71
Cadh Deficiency 56 52 73
Pcbd Deficiency 56 52 73
Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency 56 52
Hyperphenylalaninemia Due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency 52 58
Hyperphenylalaninemia Due to Dehydratase Deficiency 52 58
Pterin-4 Alpha-Carbinolamine Dehydratase Deficiency 52 58
Hpabh4d 56 73
Tetrahydrobiopterin -Deficient Hyperphenylalaninemia Due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency 52
Hyperphenylalaninemia Tetrahydrobiopterin-Deficient Due to Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency 73
Hyperphenylalaninemia Tetrahydrobiopterin-Deficient Due to Phs Deficiency 73
Pterin-4-Alpha-Carbinolamine Dehydratase Deficiency 73
Hyperphenylalaninemia, Bh4-Deficient, Type D 39
Dehydratase Deficiency 52
Phs Deficiency 73

Characteristics:

Orphanet epidemiological data:

58
pterin-4 alpha-carbinolamine dehydratase deficiency
Inheritance: Autosomal recessive; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

56
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:

31
hyperphenylalaninemia, bh4-deficient, d:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

OMIM 56 264070
MeSH 43 D010661
ICD10 via Orphanet 33 E70.1
UMLS via Orphanet 72 C1849700
Orphanet 58 ORPHA1578
MedGen 41 C1849700
UMLS 71 C1849700

Summaries for Hyperphenylalaninemia, Bh4-Deficient, D

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1578 Definition Dehydratase deficiency or pterin-4 alpha-carbinolamine dehydratase (PCD) is considered a transient and benign form of hyperphenylalaninemia due to tetrahydrobiopterin deficiency (see this term), characterized by muscular hypotonia , irritability (detected by EEG ), slow acquisition of psychomotor skills, age-dependent movement disorders, including dystonia and an accompanying excretion of 7-substituted pterins. Neurological developement is normal with dietary control of blood phenyalanine. PCD is inherited in an autosomal recessive manner. Visit the Orphanet disease page for more resources.

MalaCards based summary : Hyperphenylalaninemia, Bh4-Deficient, D, also known as hyperphenylalaninemia with primapterinuria, is related to aminolevulinic acid dehydratase deficiency porphyria and aminolevulinate dehydratase deficiency porphyria. An important gene associated with Hyperphenylalaninemia, Bh4-Deficient, D is PCBD1 (Pterin-4 Alpha-Carbinolamine Dehydratase 1). Affiliated tissues include testes, and related phenotypes are muscular hypotonia and hypertonia

OMIM : 56 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)

UniProtKB/Swiss-Prot : 73 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

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



Diseases related to Hyperphenylalaninemia, Bh4-Deficient, D

Symptoms & Phenotypes for Hyperphenylalaninemia, Bh4-Deficient, D

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

31 (showing 7, show less)
# Description HPO Frequency HPO Source Accession
1 muscular hypotonia 31 HP:0001252
2 hypertonia 31 HP:0001276
3 tremor 31 HP:0001337
4 motor delay 31 HP:0001270
5 generalized hypotonia 31 HP:0001290
6 hyperphenylalaninemia 31 HP:0004923
7 transient hyperphenylalaninemia 31 HP:0008297

Symptoms via clinical synopsis from OMIM:

56
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

Search Clinical Trials , 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 29 PCBD1

Anatomical Context for Hyperphenylalaninemia, Bh4-Deficient, D

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

40
Testes

Publications for Hyperphenylalaninemia, Bh4-Deficient, D

Articles related to Hyperphenylalaninemia, Bh4-Deficient, D:

(showing 12, show less)
# Title Authors PMID Year
1
Recessive mutations in PCBD1 cause a new type of early-onset diabetes. 6 56
24848070 2014
2
Mutations in the pterin-4alpha-carbinolamine dehydratase (PCBD) gene cause a benign form of hyperphenylalaninemia. 56 6
9760199 1998
3
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). 6 56
9585615 1998
4
Mutation in the 4a-carbinolamine dehydratase gene leads to mild hyperphenylalaninemia with defective cofactor metabolism. 6 56
8352282 1993
5
Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting. 61 56
24204001 2014
6
Characterization of the wild-type form of 4a-carbinolamine dehydratase and two naturally occurring mutants associated with hyperphenylalaninemia. 6
8618906 1995
7
Suspected pterin-4a-carbinolamine dehydratase deficiency: hyperphenylalaninaemia due to inhibition of phenylalanine hydroxylase by tetrahydro-7-biopterin. 56
1405480 1992
8
Hyperphenylalaninaemia presumably due to carbinolamine dehydratase deficiency: loading tests with pterin derivatives. 56
1405481 1992
9
A new variant of biopterin deficiency. 56
3200274 1988
10
New variant of hyperphenylalaninaemia with excretion of 7-substituted pterins. 56
3234449 1988
11
Primapterin, anapterin, and 6-oxo-primapterin, three new 7-substituted pterins identified in a patient with hyperphenylalaninemia. 56
3382399 1988
12
Neonatal hyperphenylalaninaemia presumably caused by a new variant of biopterin synthetase deficiency. 56
3366132 1988

Variations for Hyperphenylalaninemia, Bh4-Deficient, D

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

6 (showing 21, show less) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PCBD1 NM_000281.4(PCBD1):c.313T>C (p.Ter105Gln)SNV Pathogenic 428616 rs770334825 10:72643709-72643709 10:70883952-70883952
2 PCBD1 NM_000281.4(PCBD1):c.272del (p.Asn91fs)deletion Pathogenic 802585 10:72643750-72643750 10:70883993-70883993
3 PCBD1 NM_000281.4(PCBD1):c.244T>C (p.Cys82Arg)SNV Pathogenic 16796 rs104894177 10:72643778-72643778 10:70884021-70884021
4 PCBD1 NM_000281.4(PCBD1):c.236C>T (p.Thr79Ile)SNV Pathogenic 16797 rs121913014 10:72643786-72643786 10:70884029-70884029
5 PCBD1 NM_000281.4(PCBD1):c.292C>T (p.Gln98Ter)SNV Pathogenic 16799 rs121913015 10:72643730-72643730 10:70883973-70883973
6 PCBD1 NM_000281.4(PCBD1):c.259G>T (p.Glu87Ter)SNV Likely pathogenic 16795 rs104894172 10:72643763-72643763 10:70884006-70884006
7 PCBD1 NM_000281.4(PCBD1):c.*116C>TSNV Uncertain significance 300343 rs544135564 10:72643591-72643591 10:70883834-70883834
8 PCBD1 NM_000281.4(PCBD1):c.*107C>TSNV Uncertain significance 879954 10:72643600-72643600 10:70883843-70883843
9 PCBD1 NM_000281.4(PCBD1):c.179T>C (p.Leu60Pro)SNV Uncertain significance 533871 rs768330993 10:72644946-72644946 10:70885189-70885189
10 PCBD1 NM_000281.4(PCBD1):c.-27C>GSNV Uncertain significance 300349 rs573430589 10:72648317-72648317 10:70888560-70888560
11 PCBD1 NM_000281.4(PCBD1):c.*29G>ASNV Uncertain significance 300346 rs539645507 10:72643678-72643678 10:70883921-70883921
12 PCBD1 NM_000281.4(PCBD1):c.205G>A (p.Val69Met)SNV Uncertain significance 300347 rs200188190 10:72644920-72644920 10:70885163-70885163
13 PCBD1 NM_000281.4(PCBD1):c.-15G>CSNV Uncertain significance 300348 rs886047114 10:72648305-72648305 10:70888548-70888548
14 PCBD1 NM_000281.4(PCBD1):c.*114G>ASNV Likely benign 300344 rs562433724 10:72643593-72643593 10:70883836-70883836
15 PCBD1 NM_000281.4(PCBD1):c.263G>A (p.Arg88Gln)SNV Likely benign 242621 rs115117837 10:72643759-72643759 10:70884002-70884002
16 PCBD1 NM_000281.4(PCBD1):c.204C>T (p.Asn68=)SNV Likely benign 722191 10:72644921-72644921 10:70885164-70885164
17 PCBD1 NM_000281.4(PCBD1):c.*253T>ASNV Benign 300342 rs77029400 10:72643454-72643454 10:70883697-70883697
18 PCBD1 NM_000281.4(PCBD1):c.*36G>ASNV Benign 300345 rs9712 10:72643671-72643671 10:70883914-70883914
19 PCBD1 NM_000281.4(PCBD1):c.79G>T (p.Glu27Ter)SNV no interpretation for the single variant 242620 rs727505360 10:72645611-72645611 10:70885854-70885854
20 PCBD1 NM_000281.4(PCBD1):c.210_212CAA[1] (p.Asn71del)short repeat not provided 91906 rs397518415 10:72644910-72644912 10:70885153-70885155
21 PCBD1 NM_000281.4(PCBD1):c.289G>A (p.Glu97Lys)SNV not provided 91907 rs397518416 10:72643733-72643733 10:70883976-70883976

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

73 (showing 3, show less)
# 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

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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