Variant analysis of HPD genes from two families showing elevated tyrosine upon newborn screening by tandem mass spectrometry (MS/MS)

• Published in: Journal of pediatric endocrinology & metabolism : JPEM Vol. 33; no. 4; p. 563
• Main Authors: Zhao, Dehua, Tian, Yuan, Li, Xiaole, Ni, Min, Zhu, Xinyun, Jia, Liting
• Format: Journal Article
• Language: English
• Published: Germany 28-04-2020
• Subjects: 4-Hydroxyphenylpyruvate Dioxygenase - genetics; Family; Female; Humans; Infant, Newborn; Male; Mixed Function Oxygenases - blood; Mixed Function Oxygenases - deficiency; Mixed Function Oxygenases - genetics; Mutation; Neonatal Screening - methods; Tandem Mass Spectrometry; Tyrosine - blood; Tyrosinemias - blood; Tyrosinemias - diagnosis; Tyrosinemias - genetics; HPD gene; elevated tyrosine; tandem mass spectrometry
• ISSN: 2191-0251
• DOI: 10.1515/jpem-2019-0498

Background Alterations in the structure and activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) are causally related to two different metabolic disorders: recessively inherited tyrosinemia type III and dominantly inherited hawkinsinuria. The aim of this study was to provide a new perspective for the clinical understanding of the pathogenesis of tyrosinemia type III or hawkinsinuria. Case presentation A full-term newborn baby born after a safe pregnancy and childbirth with a birth weight of 3200 g and another full-term baby born after a safe pregnancy and childbirth with a birth weight of 2800 g are reported and analysed. DNA extraction, next-generation sequencing, bioinformatics analysis, Sanger sequencing and biochemical analysis were performed. One patient with a heterozygous HPD gene (NM_002150.2) c.460G > A mutation and one patient with a heterozygous HPD gene (NM_002150.2) c.248delG mutation showing elevated tyrosine levels upon newborn screening by tandem mass spectrometry (MS/MS) are reported. Conclusions The HPD gene may not be a strictly autosomal recessive pathogenic gene, which provides a new perspective for the clinical understanding of the pathogenesis of tyrosinemia type III or hawkinsinuria.