HPANBH4
MCID: HYP722
MIFTS: 23

Hyperphenylalaninemia, Mild, Non-Bh4-Deficient (HPANBH4)

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

Aliases & Classifications for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

MalaCards integrated aliases for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient:

Name: Hyperphenylalaninemia, Mild, Non-Bh4-Deficient 57 72 29 6 39
Hpanbh4 57 72
Non-Phenylketonuric Non-Bh4-Deficiency Hyperphenylalaninemia 58
Hyperphenylalaninemia Due to Dnajc12 Deficiency 58

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
variable age at onset
variable neurologic features
favorable response to treatment with neurotransmitter precursors and bh4 supplementation
favorable response to l-dopa treatment in those with parkinsonism
no defect in bh4 metabolism


HPO:

31
hyperphenylalaninemia, mild, non-bh4-deficient:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

OMIM® : 57 Mild non-BH4-deficient hyperphenylalaninemia (HPANBH4) is an autosomal recessive disorder characterized by increased serum phenylalanine (HPA) usually detected by newborn screening and associated with highly variable neurologic defects, including movement abnormalities, such as dystonia, and variably impaired intellectual development. Laboratory analysis shows dopamine and serotonin deficiencies in the cerebrospinal fluid, and normal tetrahydrobiopterin (BH4) metabolism. Evidence suggests that treatment with BH4 and neurotransmitter precursors can lead to clinical improvement or even prevent the neurologic defects if started in infancy (summary by Anikster et al., 2017). The phenotype is highly variable: some patients may present with later onset of juvenile or young adult nonprogressive dopa-responsive parkinsonism reminiscent of early-onset Parkinson disease (168600). These patients benefit from treatment with L-dopa (summary by Straniero et al., 2017). In a review of HPA, Blau et al. (2018) noted that molecular screening for DNAJC12 mutations should be mandatory in patients in whom deficiencies of PAH (612349) and BH4 metabolism have been excluded. (617384) (Updated 05-Apr-2021)

MalaCards based summary : Hyperphenylalaninemia, Mild, Non-Bh4-Deficient, is also known as hpanbh4. An important gene associated with Hyperphenylalaninemia, Mild, Non-Bh4-Deficient is DNAJC12 (DnaJ Heat Shock Protein Family (Hsp40) Member C12). Related phenotypes are nystagmus and global developmental delay

UniProtKB/Swiss-Prot : 72 Hyperphenylalaninemia, mild, non-BH4-deficient: An autosomal recessive disorder characterized by increased serum phenylalanine, normal BH4 metabolism, and highly variable neurologic defects, including movement abnormalities and intellectual disability.

Related Diseases for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

Symptoms & Phenotypes for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

Human phenotypes related to Hyperphenylalaninemia, Mild, Non-Bh4-Deficient:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 nystagmus 31 very rare (1%) HP:0000639
2 global developmental delay 31 very rare (1%) HP:0001263
3 delayed speech and language development 31 very rare (1%) HP:0000750
4 intellectual disability, mild 31 very rare (1%) HP:0001256
5 attention deficit hyperactivity disorder 31 very rare (1%) HP:0007018
6 muscular hypotonia of the trunk 31 very rare (1%) HP:0008936
7 parkinsonism 31 very rare (1%) HP:0001300
8 limb hypertonia 31 very rare (1%) HP:0002509
9 oculogyric crisis 31 very rare (1%) HP:0010553
10 hypertonia 31 HP:0001276
11 broad-based gait 31 HP:0002136
12 generalized hypotonia 31 HP:0001290
13 bradykinesia 31 HP:0002067

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
nystagmus
oculogyric crises

Neurologic Behavioral Psychiatric Manifestations:
anxiety
autistic features
depression

Laboratory Abnormalities:
increased serum phenylalanine
decreased dopamine and serotonin metabolites in the cerebrospinal fluid

Neurologic Central Nervous System:
tremor
intellectual disability, mild
dystonia
broad-based gait
rigidity
more
Muscle Soft Tissue:
hypotonia

Clinical features from OMIM®:

617384 (Updated 05-Apr-2021)

Drugs & Therapeutics for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

Search Clinical Trials , NIH Clinical Center for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

Genetic Tests for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

Genetic tests related to Hyperphenylalaninemia, Mild, Non-Bh4-Deficient:

# Genetic test Affiliating Genes
1 Hyperphenylalaninemia, Mild, Non-Bh4-Deficient 29 DNAJC12

Anatomical Context for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

Publications for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

Articles related to Hyperphenylalaninemia, Mild, Non-Bh4-Deficient:

# Title Authors PMID Year
1
DNAJC12-associated developmental delay, movement disorder, and mild hyperphenylalaninemia identified by whole-exome sequencing re-analysis. 57 6
30139987 2018
2
DNAJC12 and dopa-responsive nonprogressive parkinsonism. 57 6
28892570 2017
3
Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability. 57 6
28132689 2017
4
Dopa-responsive, nonprogressive juvenile parkinsonism: report of a case. 57 6
9159748 1997
5
Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia. 6
32333439 2020
6
DNAJC12 deficiency: A new strategy in the diagnosis of hyperphenylalaninemias. 57
29174366 2018
7
Heterogeneous clinical spectrum of DNAJC12-deficient hyperphenylalaninemia: from attention deficit to severe dystonia and intellectual disability. 6
28794131 2017
8
Beneficial Effect of BH4 Treatment in a 15-Year-Old Boy with Biallelic Mutations in DNAJC12. 61
29380259 2018

Variations for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

ClinVar genetic disease variations for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient:

6 (show all 14)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DNAJC12 NM_021800.3(DNAJC12):c.215G>C (p.Arg72Pro) SNV Pathogenic 393302 rs1035794099 GRCh37: 10:69571364-69571364
GRCh38: 10:67811606-67811606
2 DNAJC12 NM_021800.3(DNAJC12):c.158-2A>T SNV Pathogenic 393303 rs775029664 GRCh37: 10:69571423-69571423
GRCh38: 10:67811665-67811665
3 DNAJC12 NM_021800.3(DNAJC12):c.298-2A>C SNV Pathogenic 870653 GRCh37: 10:69565547-69565547
GRCh38: 10:67805789-67805789
4 DNAJC12 NM_021800.3(DNAJC12):c.502+1G>C SNV Pathogenic 870654 GRCh37: 10:69565340-69565340
GRCh38: 10:67805582-67805582
5 DNAJC12 NM_021800.3(DNAJC12):c.309G>T (p.Trp103Cys) SNV Pathogenic 870656 GRCh37: 10:69565534-69565534
GRCh38: 10:67805776-67805776
6 DNAJC12 NM_021800.3(DNAJC12):c.58_59del (p.Gly20fs) Deletion Pathogenic 636261 rs1589052989 GRCh37: 10:69597711-69597712
GRCh38: 10:67837953-67837954
7 DNAJC12 NM_021800.3(DNAJC12):c.214C>T (p.Arg72Ter) SNV Pathogenic 694073 rs569240271 GRCh37: 10:69571365-69571365
GRCh38: 10:67811607-67811607
8 DNAJC12 NM_021800.3(DNAJC12):c.187A>T (p.Lys63Ter) SNV Pathogenic 694074 rs761235755 GRCh37: 10:69571392-69571392
GRCh38: 10:67811634-67811634
9 DNAJC12 NM_021800.3(DNAJC12):c.79-2A>G SNV Pathogenic 694075 rs1277990552 GRCh37: 10:69583152-69583152
GRCh38: 10:67823394-67823394
10 DNAJC12 NM_021800.3(DNAJC12):c.596G>T (p.Ter199Leu) SNV Pathogenic 694072 rs1273776043 GRCh37: 10:69556875-69556875
GRCh38: 10:67797117-67797117
11 DNAJC12 NM_021800.3(DNAJC12):c.298-968_503-2603del Deletion Pathogenic 393301 GRCh37: 10:69559570-69566512
GRCh38: 10:67799812-67806754
12 DNAJC12 NM_021800.3(DNAJC12):c.85del (p.Gln29fs) Deletion Pathogenic 694071 rs770562664 GRCh37: 10:69583144-69583144
GRCh38: 10:67823386-67823386
13 DNAJC12 NM_021800.3(DNAJC12):c.524G>A (p.Trp175Ter) SNV Pathogenic 870655 GRCh37: 10:69556947-69556947
GRCh38: 10:67797189-67797189
14 DNAJC12 NM_021800.3(DNAJC12):c.124C>T (p.His42Tyr) SNV Uncertain significance 802579 rs1055578473 GRCh37: 10:69583105-69583105
GRCh38: 10:67823347-67823347

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

72
# Symbol AA change Variation ID SNP ID
1 DNAJC12 p.Arg72Pro VAR_078797 rs103579409

Expression for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

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

Pathways for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

GO Terms for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

Sources for Hyperphenylalaninemia, Mild, Non-Bh4-Deficient

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