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

doi:10.1016/j.heliyon.2024.e27050

Genotype characterization of tetrahydrobiopterin deficiency in two Tibetan children

Heliyon. 2024 Feb 24;10(5):e27050. doi: 10.1016/j.heliyon.2024.e27050. eCollection 2024 Mar 15.

Authors

Shuyao Zhu¹, Qi Hu², Yunxia Yang², Hui Zhu¹, Jin Wang³, Zemin Luo¹, Mincai Ou², Ai Chen¹, Yu Huang¹, Fu Xiong¹, Jiaji Zhou¹, Jinglin Liu², Xunming Lei¹, Lan Zeng³

Affiliations

¹ Department of Pediatrics, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China.
² Department of Neonatal Screening Centre in Sichuan Province Maternity and Child Health Care Hospital, Chengdu, Sichuan, China.
³ Department of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, 610031, China.

Abstract

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 <120 μmol). The biopterin(B) level was 0.19 mmol/molCr (reference range: 0.42-1.92 mmol/molCr), with a B% of 5.67% (reference range: 19.8%-50.3%). Gene sequencing revealed a homozygous missense variant [NM_000317.3 (PTS): c.259C > 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.

Keywords: Case report; PTS; QDPR; Tetrahydrobiopterin (BH4) -deficient; Tibetan.

Publication types

Case Reports