6-pyruvoyl-tetrahydropterin synthase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: 6-&#64
PYRUVOYL-TETRAHYDROPTERIN SYNTHASE DEFICIENCY
PTS DEFICIENCY HYPERPHENYLALANINEMIA, BH4-DEFICIENT, DUE TO PARTIAL PTS DEFICIENCY, INCLUDED
HYPERPHENYLALANINEMIA, TETRAHYDROBIOPTERIN-DEFICIENT, DUE TO PTS DEFICIENCY
HPABH4A
Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency
Number of Symptoms 39
OrphanetNr: 13
OMIM Id: 261640
ICD-10: E70.1
UMLs: C0878676
MeSH: C535325
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
18060820 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Hyperphenylalaninemia
 -Rare genetic disease
 -Rare neurologic disease

Comment:

The patients are classified as affected by generalized (severe) or peripheral (mild) form of PTPS deficiency (PTPSd). In GTPCH, PCD and PTPS-deficient patients, blood Phe normalizes (<120 μmol/L) within 4–8 h after the BH4 (tetrahydrobiopterin) challenge, but patients with DHPR deficiency only show a moderate Phe reduction (51 % of initial blood levels) during the same time period. (PMID:22729819)

Symptom Information: Sort by abundance 

1
 (HPO:0003110) Abnormality of urine homeostasis 20059486 IBIS 9 / 7739
2
 (HPO:0003781) Excessive salivation 18060820 IBIS 15 / 7739
3
 (HPO:0000252) Microcephaly 18060820 IBIS 832 / 7739
4
 (HPO:0002172) Postural instability 18060820 IBIS 22 / 7739
5
 (HPO:0001300) Parkinsonism 20059486 IBIS 75 / 7739
6
 (HPO:0001332) Dystonia 16161143; 22729819 IBIS 197 / 7739
7
 (HPO:0002311) Incoordination 20059486; 22729819 IBIS 84 / 7739
8
 (HPO:0002921) Abnormality of the cerebrospinal fluid 20059486 IBIS 6 / 7739
9
 (HPO:0010553) Oculogyric crisis 20059486 IBIS 5 / 7739
10
 (HPO:0001266) Choreoathetosis 16161143; 18060820 IBIS 57 / 7739
11
 (HPO:0001249) Intellectual disability 20059486 IBIS 1089 / 7739
12
 (HPO:0002063) Rigidity 20059486 IBIS 92 / 7739
13
 (HPO:0001270) Motor delay 20059486 IBIS 322 / 7739
14
 (HPO:0001250) Seizures 22729819 IBIS 1245 / 7739
15
 (HPO:0002015) Dysphagia 16850690 IBIS 301 / 7739
16
 (HPO:0006887) Intellectual disability, progressive 20059486 IBIS 68 / 7739
17
 (HPO:0001337) Tremor 20059486 IBIS 200 / 7739
18
 (HPO:0000737) Irritability 18060820 IBIS 93 / 7739
19
 (HPO:0001251) Ataxia 18060820 IBIS 413 / 7739
20
 (HPO:0002344) Progressive neurologic deterioration 20059486 IBIS 27 / 7739
21
 (HPO:0002360) Sleep disturbance 20059486 IBIS 113 / 7739
22
 (HPO:0002329) Drowsiness 18060820 IBIS 19 / 7739
23
 (HPO:0001347) Hyperreflexia 18060820 IBIS 363 / 7739
24
 (HPO:0002066) Gait ataxia 18060820 IBIS 327 / 7739
25
 (HPO:0001276) Hypertonia 22729819 IBIS 317 / 7739
26
 (HPO:0002071) Abnormality of extrapyramidal motor function 16767663 IBIS 76 / 7739
27
 (HPO:0002375) Hypokinesia 18060820; 20059486 IBIS 25 / 7739
28
 (HPO:0001263) Global developmental delay 20059486 IBIS 853 / 7739
29
 (HPO:0000870) Prolactin excess 20059486 IBIS 10 / 7739
30
 (HPO:0002033) Poor suck 18060820 IBIS 37 / 7739
31
 (HPO:0001518) Small for gestational age 18060820; 22729819 IBIS 107 / 7739
32
 (HPO:0002045) Hypothermia 18060820 IBIS 27 / 7739
33
 (HPO:0001954) Episodic fever 18060820 IBIS 27 / 7739
34
 (HPO:0004923) Hyperphenylalaninemia Very frequent [IBIS] 22729819 IBIS 7 / 7739
35
 (HPO:0008936) Muscular hypotonia of the trunk 18060820; 20059486 IBIS 77 / 7739
36
 (HPO:0001252) Muscular hypotonia 22729819 IBIS 990 / 7739
37
 (OMIM) Decreased or absent PTS activity 20059486; 22729819; 3276524 IBIS 1 / 7739
38
 (OMIM) Increased neopterin in urine and CSF 20059486 IBIS 1 / 7739
39
 (OMIM) Decreased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) in CSF 20059486 IBIS 3 / 7739

Associated genes:

PTS;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4. BH4 is a cofactor for phenylalanine hydroxylase ...
Clinical Description OMIM Kaufman et al. (1978) studied a boy with what appeared to be classic phenylketonuria who showed neurologic abnormalities, including hypotonia and delayed motor development, despite good dietary control of blood levels of phenylalanine from the age of 25 ...
Molecular genetics OMIM Thony et al. (1994) identified mutations in the PTS gene (e.g., 612719.0001) in patients with BH4-deficient hyperphenylalaninemia.

Oppliger et al. (1997) identified 4 novel mutations in 4 Italian families with PTS deficiency.

Thony and ...
Population genetics OMIM Liu et al. (1998) identified 7 single-base mutations in Chinese cases of PTS-deficient hyperphenylalaninemia. In all, 38 PTS mutant alleles from 19 unrelated Chinese families were studied. Two common mutations, N52S (612719.0004) and P87S (612719.0005), accounted for 71% ...