GTP cyclohydrolase I deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: GTP CYCLOHYDROLASE I DEFICIENCY DYSTONIA, DOPA-RESPONSIVE, WITH OR WITHOUT HYPERPHENYLALANINEMIA, AUTOSOMAL RECESSIVE, INCLUDED
HYPERPHENYLALANINEMIA, TETRAHYDROBIOPTERIN-DEFICIENT, DUE TO GTP CYCLOHYDROLASE I DEFICIENCY
HPABH4B
Hyperphenylalaninemia due to GTP cyclohydrolase deficiency
GTPCH deficiency
Number of Symptoms 37
OrphanetNr: 2102
OMIM Id: 233910
ICD-10: E70.1
E79.8
UMLs: C0268467
MeSH:
MedDRA:
Snomed: 23447005

Prevalence, inheritance and age of onset:

Prevalence: 17 cases
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

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

Comment:

The phenotypic spectrum of GTPCH type I deficiency can be regarded as a continuum between the milder dominant and the severe recessive forms (PMID: 18276179). 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 20818608 IBIS 9 / 7739
2
 (HPO:0002307) Drooling 18276179 IBIS 43 / 7739
3
 (HPO:0000253) Progressive microcephaly 18276179 IBIS 37 / 7739
4
 (HPO:0000496) Abnormality of eye movement 18276179 IBIS 79 / 7739
5
 (HPO:0010553) Oculogyric crisis 18276179 IBIS 5 / 7739
6
 (HPO:0001250) Seizures 22729819; 18276179 IBIS 1245 / 7739
7
 (HPO:0001263) Global developmental delay 22729819; 18276179 IBIS 853 / 7739
8
 (HPO:0002179) Opisthotonus 22473768 IBIS 35 / 7739
9
 (HPO:0001332) Dystonia 15303002; 12552057 IBIS 197 / 7739
10
 (HPO:0002344) Progressive neurologic deterioration 18276179; 22729819 IBIS 27 / 7739
11
 (HPO:0001336) Myoclonus 22473768 IBIS 115 / 7739
12
 (HPO:0001270) Motor delay 20818608; 18276179 IBIS 322 / 7739
13
 (HPO:0002487) Hyperkinesis 15303002 IBIS 7 / 7739
14
 (HPO:0004372) Reduced consciousness/confusion 22473768 IBIS 73 / 7739
15
 (HPO:0002063) Rigidity 15303002 IBIS 92 / 7739
16
 (HPO:0002548) Parkinsonism with favorable response to dopaminergic medication 15303002; 20818608; 18276179 IBIS 13 / 7739
17
 (HPO:0001337) Tremor 20818608; 18276179 IBIS 200 / 7739
18
 (HPO:0002191) Progressive spasticity 18276179 IBIS 12 / 7739
19
 (HPO:0003785) Decreased CSF homovanillic acid 20818608 IBIS 7 / 7739
20
 (HPO:0002921) Abnormality of the cerebrospinal fluid 20818608; 18276179; 22473768 IBIS 6 / 7739
21
 (HPO:0002360) Sleep disturbance 18276179 IBIS 113 / 7739
22
 (HPO:0001249) Intellectual disability 22473768 IBIS 1089 / 7739
23
 (HPO:0002509) Limb hypertonia 20818608 IBIS 13 / 7739
24
 (HPO:0100543) Cognitive impairment 22473768 IBIS 230 / 7739
25
 (HPO:0008872) Feeding difficulties in infancy 18276179 IBIS 153 / 7739
26
 (HPO:0002033) Poor suck 18276179 IBIS 37 / 7739
27
 (HPO:0004923) Hyperphenylalaninemia 22729819; 18276179 IBIS 7 / 7739
28
 (HPO:0008297) Transient hyperphenylalaninemia 18276179 IBIS 4 / 7739
29
 (HPO:0006829) Severe muscular hypotonia 22729819 IBIS 29 / 7739
30
 (HPO:0008936) Muscular hypotonia of the trunk 20818608 IBIS 77 / 7739
31
 (OMIM) Decreased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) in CSF 20818608; 22473768 IBIS 3 / 7739
32
 (OMIM) Uncoordinated movements 22729819 IBIS 4 / 7739
33
 (OMIM) Decreased neopterin and biopterin in urine 20818608 IBIS 1 / 7739
34
 (OMIM) 5-HIAA CSF may be normal or decreased 18276179 IBIS 2 / 7739
35
 (OMIM) Decreased neopterin and biopterin in CSF 20818608; 18276179; 22473768 IBIS 1 / 7739
36
 (OMIM) [DEL]Hypertonia of the extremities 20818608 IBIS 3 / 7739
37
 (OMIM) Decreased or absent GCH1 activity 22729819; 20818608; 22473768 IBIS 1 / 7739

Associated genes:

GCH1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Niederwieser et al. (1984) reported a 4-year-old girl with hyperphenylalaninemia, severe developmental retardation, severe muscular hypotonia of the trunk and hypertonia of the extremities, convulsions, and frequent episodes of hyperthermia without infection. Urinary excretion of neopterin, biopterin, pterin, ...
Molecular genetics OMIM - BH4-deficient Hyperphenylalaninemia B

In a male infant with HPA due to GCH1 deficiency, Blau et al. (1995) identified a homozygous mutation in the GCH1 gene (600225.0017).

In a female infant with BH4-deficient HPA, ...