A sibling case of hyperphenylalaninemia due to a deficiency of dihydropteridine reductase: Biochemical and pathological findings.

Tada, Keiya; Narisawa, Kuniaki; Arai, Noriyuki; Ogasawara, Yoshihiko; Ishizawa, S.

doi:10.1620/tjem.132.123

Cited by 29 publications

(18 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14,15 The first patients with HPA dependent on DHPR deficiency were two Japanese siblings, reported by Tada et al in 1969, 16 but enzymatically characterized in 1980. 17 The original report of a definite diagnosis of DHPR deficiency was made by Kaufman et al in 1975 in an American 14-month-old male infant who developed seizures and other neurological symptoms despite adequate treatment coherent with the previous diagnosis of PKU. 18 A ''central'' form of DHPR deficiency was recently reported following the observation of two Turkish boys presenting with suggestive neurological and cerebrospinal fluid (CSF) picture of pterin disorder, but without HPA.…”

Section: B H 4 F U N C T I O N S a N D D E F I C I E N C Ymentioning

confidence: 99%

Dihydropteridine reductase deficiency in man: From biology to treatment

Ponzone

Spada

Ferraris

et al. 2003

Medicinal Research Reviews

View full text Add to dashboard Cite

In 1975, dihydropteridine reductase (DHPR) deficiency was first recognized as a cause of tetrahydrobiopterin (BH(4)) deficiency, leading to hyperphenylalaninemia (HPA) and impaired biogenic amine deficiency. So far, more than 150 patients scattered worldwide have been reported and major progresses have been made in the understanding of physiopathology, screening, diagnosis, treatment, and molecular genetics of this inherited disease. Present knowledge on different aspects of DHPR deficiency, largely derived from authors' personal experience, is traced in this article.

show abstract

Section: B H 4 F U N C T I O N S a N D D E F I C I E N C Ymentioning

confidence: 99%

Dihydropteridine reductase deficiency in man: From biology to treatment

Ponzone

Spada

Ferraris

et al. 2003

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…However, their patient also had Fahr disease (vascular calcinosis of the brain) and died at age 17 months. The cases reported by both Tada et al [1980] and Smith et al [1985] had DHPR deficiency. Our patient with bilateral calcifications, then, is only the second report involving a classical PKU patient.…”

Section: Discussionmentioning

confidence: 90%

“…Brain calcification, reported in patients with dihydropteridine reductase (DHPR) deficiency [Tada et al, 1980;Smith et al, 19851, has been reported in only one classical PKU patient [Parker and Landing, 1977; the patient also had Fahr disease]. We report on three untreated PKU patients with cataracts.…”

Section: Introductionmentioning

confidence: 77%

Three cases of untreated classical PKU: A report on cataracts and brain calcification

Kawashima

Kawano²,

Masaki³

et al. 1988

Am. J. Med. Genet.

View full text Add to dashboard Cite

There are only four previous reports of cataracts in untreated classical phenylketonuria (PKU) patients. Brain calcification, which has been known to occur in patients with dihydropteridine reductase (DHPR) deficiency, has been reported, as far as we know, in only one (albeit unusual) case. We report on three patients with untreated classical PKU; all have cataracts and normal serum levels of glucose and galactose. One of the patients (whose endocrinological tests and biochemistry including folate were normal) has bilateral brain calcifications remarkably similar to that seen in DHPR deficiency. To what extent cataracts and brain calcification occur with classical PKU is unknown because of the lack of case reports addressing these symptoms. Our cases combined with previous reports call attention to the fact that they may be frequently overlooked manifestations of classical PKU.

show abstract

“…It showed that both substrates docked to similar binding sites of RatDHPR as seen in DicDHPR, which suggests that RatDHPR might also be able to catalyze the synthesis of DH 4 from q-DH 2 as well as that of BH 4 from q-BH 2 . To further investigate the possibility of q-DH 2 catalysis to DH 4 , we have carried out the activity assay for RatDHPR using q-DH 2 (Fig. 5).…”

Section: Q-dh 2 Catalysis By Rat Dhprmentioning

confidence: 99%

“…DHPR dysfunction in human is one of the causes of malignant hyperphenylalaninemia due to BH 4 deficiency [2]. BH 4 is a well-known essential cofactor for nitric oxide synthases [3] and aromatic amino acid hydroxylases [4,5], which play vital roles in the biosynthesis of nitric oxide and monoamine neurotransmitters, respectively.…”

Section: Introductionmentioning

confidence: 99%

Structural insights into the dual substrate specificities of mammalian andDictyosteliumdihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin

Chen¹,

Kim²,

Zhuang³

et al. 2011

FEBS Letters

View full text Add to dashboard Cite

Edited by Christian GriesingerKeywords: Dihydropteridine reductase Quinonoid (6R)-D-threo-dihydrobiopterin Tetrahydrobiopterin Crystal structure Dictyostelium discoideum a b s t r a c tUp to now, D-threo-tetrahydrobiopterin (DH 4 , dictyopterin) was detected only in Dictyostelium discoideum, while the isomer L-erythro-tetrahydrobioterin (BH 4 ) is common in mammals. To elucidate the mechanism of DH 4 regeneration by D. discoideum dihydropteridine reductase (DicDHPR), we have determined the crystal structure of DicDHPR complexed with NAD + at 2.16 Å resolution. Significant structural differences from mammalian DHPRs are found around the coenzyme binding site, resulting in a higher K m value for NADH (K m = 46.51 ± 0.4 lM) than mammals. In addition, we have found that rat DHPR as well as DicDHPR could bind to both substrates quinonoid-BH 2 and quinonoid-DH 2 by docking calculations and have confirmed their catalytic activity by in vitro assay. Structured summary of protein interactions:DHPR binds to DHPR by X-ray crystallography (View interaction)

show abstract

A sibling case of hyperphenylalaninemia due to a deficiency of dihydropteridine reductase: Biochemical and pathological findings.

Cited by 29 publications

References 12 publications

Dihydropteridine reductase deficiency in man: From biology to treatment

Dihydropteridine reductase deficiency in man: From biology to treatment

Three cases of untreated classical PKU: A report on cataracts and brain calcification

Structural insights into the dual substrate specificities of mammalian andDictyosteliumdihydropteridine reductases toward two stereoisomers of quinonoid dihydrobiopterin

Contact Info

Product

Resources

About