Details of Disease

General Information of Disease (ID: DIS1IC3E)

• Disease Name: Dihydropteridine reductase deficiency
• Synonyms: quinoid dihydropteridine reductase deficiency; DHPR deficiency; Qdpr deficiency; hyperphenylalaninemia, BH-4-deficient, C; hyperphenylalaninemia, tetrahydrobiopterin-deficient, due to DHPR deficiency; hyperphenylalaninemia, BH4-deficient, C; HPABH4C; hyperphenylalaninemia, BH4-deficient C; disorder of 6,7-dihydropteridine reductase activity; phenylketonuria type 2; hyperphenylalaninemia, Bh4-deficient, type C; PKU type 2; 6,7-dihydropteridine reductase activity disease; hyperphenylalaninemia due to dihydropteridine reductase deficiency; dihydropteridine reductase deficiency
• Definition: Dihydropteridine reductase (DHPR) deficiency is a severe form of hyperphenylalaninemia (HPA) due to impaired regeneration of tetrahydrobiopterin (BH4), leading to decreased levels of neurotransmitters (dopamine, serotonin) and folate in cerebrospinal fluid, and causing neurological symptoms such as psychomotor delay, hypotonia, seizures, abnormal movements, hypersalivation, and swallowing difficulties.
• Disease Hierarchy:
  DISJSFZR: Tetrahydrobiopterin metabolic process disease
  DISWD40R: Disease
  DISCQU4G: Hyperphenylalaninemia
  DIS1IC3E: Dihydropteridine reductase deficiency
• Disease Identifiers:
  MONDO ID: MONDO_0009862
  MESH ID: D010661
  UMLS CUI: C0268465
  OMIM ID: 261630
  MedGen ID: 75682
  Orphanet ID: 226
  SNOMED CT ID: 58256000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GCH1	TTLSWP6	Strong	Genetic Variation	[1]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
SPR	DEJVDAT	Strong	Genetic Variation	[2]

This Disease Is Related to 3 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
NIF3L1	OT4MP90J	Strong	Genetic Variation	[1]
PTS	OTTYWQXR	Strong	Biomarker	[3]
QDPR	OTSKOIUX	Definitive	Autosomal recessive	[4]

References

• [1] BH(4) deficiency identified in a neonatal screening program for hyperphenylalaninemia.J Pediatr (Rio J). 2018 Mar-Apr;94(2):170-176. doi: 10.1016/j.jped.2017.04.005. Epub 2017 Aug 9.
• [2] Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population.Mol Genet Metab. 2007 Mar;90(3):277-83. doi: 10.1016/j.ymgme.2006.10.013. Epub 2006 Dec 22.
• [3] Urinary sulphatoxymelatonin as a biomarker of serotonin status in biogenic amine-deficient patients.Sci Rep. 2017 Nov 7;7(1):14675. doi: 10.1038/s41598-017-15063-8.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.