Genotype characterization of tetrahydrobiopterin deficiency in two Tibetan children
Shuyao Zhu,
Qi Hu,
Yunxia Yang,
Hui Zhu,
Jin Wang,
Zemin Luo,
Mincai Ou,
Ai Chen,
Yu Huang,
Fu Xiong,
Jiaji Zhou,
Jinglin Liu,
Xunming Lei,
Lan Zeng
Affiliations
Shuyao Zhu
Department of Pediatrics, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Qi Hu
Department of Neonatal Screening Centre in Sichuan Province Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Yunxia Yang
Department of Neonatal Screening Centre in Sichuan Province Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Hui Zhu
Department of Pediatrics, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Jin Wang
Department of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, 610031, China
Zemin Luo
Department of Pediatrics, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Mincai Ou
Department of Neonatal Screening Centre in Sichuan Province Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Ai Chen
Department of Pediatrics, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Yu Huang
Department of Pediatrics, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Fu Xiong
Department of Pediatrics, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Jiaji Zhou
Department of Pediatrics, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Jinglin Liu
Department of Neonatal Screening Centre in Sichuan Province Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Xunming Lei
Department of Pediatrics, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China
Lan Zeng
Department of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, 610031, China; Corresponding author. Department of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, No. 290, Sha Yan Xi 2nd Road, Chengdu, Sichuan, 10031, China.
Background: Tetrahydrobiopterin (BH4) deficiency is a rare cause of hyperphenylalaninemia (HPA). The incidence of this condition varies based on region and ethnicity. In the early stages, patients typically do not exhibit any symptoms, and HPA is identified only through newborn screening for diseases. It is important to distinguish BH4 deficiency from phenylketonuria (PKU, MIM # 261600). Timely diagnosis and treatment of BH4 deficiency are crucial for the prognosis of patients. Case presentation: We present two rare cases of Chinese Tibetan children with BH4D, diagnosed through biochemical tests and genetic sequencing. Case 1 is a male infant, 2 months old, with a newborn screening (NBS) Phe level of 1212 μmol/L (reference range T (p.Pro87Ser), rs104894276, ClinVar variation ID: 480]. The patient was treated with a Phe-reduced diet and oral sapropterin, madopar and is currently 3 years and 4 months old, showing mild global developmental delay. Case 2 is a 40-day-old female infant with a Phe level of 2442.11 μmol/L and dihydropteridine reductase (DHPR) activity of 0.84 nmol/(min. 5 mm disc) (reference range: 1.02–3.35 nmol/min.5 mm disc. Gene sequencing revealed a compound heterozygous genotype [NM_000320.3(QDPR): c.68G > A (p.Gly23Asp), rs104893863, ClinVar Variation ID: 490] and [NM_000320.3(QDPR) c.419C > A (p. Ala140Asp), ClinVar ID: 2444501]. The patient was treated with a Phe-reduced diet and oral madopar, 5-hydroxytryptophan. At the age of 1 year, she exhibited severe global developmental delay with seizures. Conclusion: We identified and treated two cases of BH4D in Tibetan populations in China, marking the first confirmed instances. Our report emphasizes the significance of conducting differential diagnosis tests for BH4D.
