Medical Genetic Center, Changzhi Maternal and Child Health Care Hospital, Changzhi, Shanxi, China.
Department of Pediatrics, Changzhi Maternal and Child Health Care Hospital, Changzhi, Shanxi, China.
Mol Genet Genomic Med. 2024 Jan;12(1):e2298. doi: 10.1002/mgg3.2298. Epub 2023 Oct 10.
Hereditary tyrosinemia type III (HT III) is an extremely rare form of tyrosinemia, characterized by autosomal recessive inheritance and biallelic mutations in the HPD gene. The clinical presentation of HT III is variable and poorly understood, with symptoms ranging from developmental delay and intellectual impairment to seizures and intermittent ataxia. This study aimed to provide further insights into the clinical and genetic characteristics of HT III.
A 3-year-old girl, identified through newborn screening, was diagnosed with HT III using targeted next-generation sequencing. A comprehensive literature review was conducted, and the clinical, biochemical, and genetic findings of previously reported HT III patients were summarized and analyzed.
The genetic analysis of the proband revealed compound heterozygous mutations in the HPD gene such as c.731C>T (p.A244V) and c.656C>T (p.T219M). Notably, the HPD p.A244V mutation had not been previously documented in public databases or the scientific literature. Bioinformatics analysis classified both variants as pathogenic variants. The patient exhibited persistent tyrosinemia, elevated levels of related metabolite derivatives, confirming the diagnosis of HT III. The review of previously published cases contributed to a better understanding of the clinical and genetic characteristics associated with HT III.
Early diagnosis and prompt treatment in infancy are crucial for managing HT III effectively. Dietary therapy, particularly during childhood, plays a significant role in disease management. The findings from this study enhance our understanding of the genotype-phenotype associations in HT III and emphasize the importance of early intervention for improved patient outcomes.
遗传性酪氨酸血症 III 型（HT III）是一种极为罕见的酪氨酸血症，呈常染色体隐性遗传，HPD 基因突变呈双等位基因。HT III 的临床表现多样且了解甚少，症状范围从发育迟缓、智力障碍到癫痫发作和间歇性共济失调。本研究旨在进一步了解 HT III 的临床和遗传特征。
通过新生儿筛查发现一名 3 岁女孩，使用靶向下一代测序诊断为 HT III。进行了全面的文献复习，并总结和分析了以前报道的 HT III 患者的临床、生化和遗传发现。
对先证者的基因分析显示 HPD 基因存在复合杂合突变，如 c.731C>T（p.A244V）和 c.656C>T（p.T219M）。值得注意的是，HPD p.A244V 突变尚未在公共数据库或科学文献中记录。生物信息学分析将这两种变体均归类为致病性变体。患者表现出持续性酪氨酸血症，相关代谢物衍生物水平升高，证实了 HT III 的诊断。对以前发表的病例的回顾有助于更好地了解与 HT III 相关的临床和遗传特征。
婴儿期的早期诊断和及时治疗对于有效管理 HT III 至关重要。饮食疗法，尤其是在儿童期，对疾病管理起着重要作用。本研究的结果增强了我们对 HT III 基因型-表型关联的理解，并强调了早期干预对改善患者预后的重要性。
