Abstract | OBJECTIVE: METHODS: (1) A male patient presented with poor hand control, seizure, hypotonia and mental retardation since five-month after birth. His phenylalanine (Phe) level was 600 micromol/L and he was diagnosed as hyperphenylalaninemia at the age of one year and six-month. (2) This patient was subjected to combined Phe (100 mg/kg) and BH4 (20 mg/kg) loading test, to evaluate the degree of Phe level response to BH4. Urinary neopterin and biopterin analysis as well as the determination of DHPR activity in dried blood spot were also performed. (3) The blood DNA samples of the patient and his parents were collected to amplify the seven exons of QDPR gene using related primers, and the amplified products were directly sequenced for mutation analysis. (4) The patient was treated with BH4 or with a combined small amount of Phe-free special milk, neurotransmitter precursors and folic acid after the diagnosis and was followed up for clinical effects of treatment. RESULTS: (1) The basic Phe level was 476 micromol/L, then it increased to 1355 micromol/L at 3 h after taking Phe and slowly decreased to 610 micromol/L at 24h after taking BH4. (2) The basic urinary neopterin and biopterin were 2.92 mmol/mol Cr (normally < 2.61 mmol/mol Cr) and 7.44 mmol/molCr (normally < 2.67 mmol/mol Cr) respectively, and biopterin percentage was 71.79% (normally 42.7% - 75.9%). The patient had higher biopterin level. (3) The DHPR activity of this patient was (0.27 - 0.51) nmol/(min.5 mm disc) which were 6.11% - 10.6% of normal control, so he was diagnosed as DHPR deficiency. (4) The analysis of QDPR gene mutation showed that the patient carries missense mutation c.515C > T (P172L) from his father and nonsense mutation c.661C > T (R221X) from his mother. The c.515C > T is not reported before, we also did not find this mutation in 50 normal children. (5) The patient started to be treated with large dosage of BH4 (10 - 20) mg/(kg.d) or BH4 combined with small amounts of Phe-free milk, neurotransmitter precursors L-dopa (3 - 5) mg/(kg.d) plus carbidopa, 5-hydroxytryptophan (3 - 5) mg/(kg.d), and folic acid 15 mg/d as well at the age of one year and six-month after the diagnosis. The seizure has disappeared, the symptoms such as hypotonia have been obviously improved and the Phe level was 60 micromol/L at the six months after the treatment in this patient. CONCLUSION:
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Authors | Jun Ye, Wen-juan Qiu, Lian-shu Han, Hui-wen Zhang, Jian-de Zhou, Xiao-lan Gao, Yu Wang, Xue-fan Gu |
Journal | Zhonghua er ke za zhi = Chinese journal of pediatrics
(Zhonghua Er Ke Za Zhi)
Vol. 46
Issue 4
Pg. 281-5
(Apr 2008)
ISSN: 0578-1310 [Print] China |
PMID | 19099731
(Publication Type: Case Reports, English Abstract, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Phenylalanine
- Dihydropteridine Reductase
- Phosphorus-Oxygen Lyases
- 6-pyruvoyltetrahydropterin synthase
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Topics |
- China
- Dihydropteridine Reductase
(genetics)
- Humans
- Infant
- Male
- Mutation
- Phenylalanine
(blood)
- Phenylketonurias
(diagnosis, genetics, therapy)
- Phosphorus-Oxygen Lyases
(genetics)
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