Dihydropteridine reductase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: DIHYDROPTERIDINE REDUCTASE DEFICIENCY
HYPERPHENYLALANINEMIA, TETRAHYDROBIOPTERIN-DEFICIENT, DUE TO DHPR DEFICIENCY
DHPR DEFICIENCY
QDPR DEFICIENCY
QUINOID DIHYDROPTERIDINE REDUCTASE DEFICIENCY
HPABH4C
Phenylketonuria type 2
Hyperphenylalaninemia due to dihydropteridine reductase deficiency
PKU type 2
Number of Symptoms 26
OrphanetNr: 226
OMIM Id: 261630
ICD-10: E70.1
UMLs: C0268465
C2936906
MeSH: C537896
MedDRA:
Snomed: 58256000

Prevalence, inheritance and age of onset:

Prevalence: > 150 cases
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

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

Comment:

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 1283784; 22729819; 25213568 IBIS 9 / 7739
2
 (HPO:0002307) Drooling 6139056 IBIS 43 / 7739
3
 (HPO:0000252) Microcephaly Very frequent [Orphanet] 1283784 IBIS 832 / 7739
4
 (HPO:0001270) Motor delay Very frequent [Orphanet] 22729819 IBIS 322 / 7739
5
 (HPO:0001328) Specific learning disability Very frequent [Orphanet] 18060820 IBIS 114 / 7739
6
 (HPO:0012656) Reduced CSF dopamine level 22729819 IBIS 1 / 7739
7
 (HPO:0002509) Limb hypertonia 22729819 IBIS 13 / 7739
8
 (HPO:0001250) Seizures 22729819; 18060820 IBIS 1245 / 7739
9
 (HPO:0003785) Decreased CSF homovanillic acid 22729819; 18060820 IBIS 7 / 7739
10
 (HPO:0001249) Intellectual disability Very frequent [Orphanet] 22729819 IBIS 1089 / 7739
11
 (HPO:0002353) EEG abnormality Frequent [IBIS] 22729819 IBIS 188 / 7739
12
 (HPO:0001263) Global developmental delay Very frequent [Orphanet] 22729819 IBIS 853 / 7739
13
 (HPO:0002921) Abnormality of the cerebrospinal fluid 22729819; 18060820 IBIS 6 / 7739
14
 (HPO:0001276) Hypertonia 22729819 IBIS 317 / 7739
15
 (HPO:0001332) Dystonia Occasional [IBIS] 22729819 IBIS 197 / 7739
16
 (HPO:0100543) Cognitive impairment Very frequent [Orphanet] 22729819 IBIS 230 / 7739
17
 (HPO:0005671) Bilateral intracranial calcifications Frequent [IBIS] 22729819 IBIS 9 / 7739
18
 (HPO:0002135) Basal ganglia calcification Frequentl [IBIS] 22729819 IBIS 37 / 7739
19
 (HPO:0004923) Hyperphenylalaninemia Very frequent [IBIS] 22729819 IBIS 7 / 7739
20
 (HPO:0001252) Muscular hypotonia 22729819 IBIS 990 / 7739
21
 (HPO:0001324) Muscle weakness 22729819 IBIS 859 / 7739
22
 (HPO:0002059) Cerebral atrophy 22729819 IBIS 171 / 7739
23
 (OMIM) Decreased or absent dihydropteridine reductase activity 22729819; 25213568 IBIS 1 / 7739
24
 (OMIM) Decreased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) in CSF 22729819; 18060820 IBIS 3 / 7739
25
 (OMIM) Increased biopterin in urine and CSF 1283784; 22729819; 25213568 IBIS 1 / 7739
26
 (OMIM) Uncoordinated movements Occasional [IBIS] 22729819 IBIS 4 / 7739

Associated genes:

QDPR;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis OMIM - Prenatal Diagnosis

Dahl et al. (1987, 1988) showed that RFLPs of the DHPR locus could be used for prenatal diagnosis.
Clinical Description OMIM Smith et al. (1975) described 3 children, 2 of them sibs, with an unusual type of phenylketonuria. All 3 (2 of them observed from the neonatal period) had a progressive neurologic illness that did not respond to a ...
Molecular genetics OMIM In a patient with dihydropteridine reductase deficiency, the offspring of consanguineous parents, Howells et al. (1990) identified homozygosity for a mutation in the QDPR gene (612676.0001).

Smooker and Cotton (1995) reviewed 12 point mutations that had ...