Abstract:

Objective To retrospectively analyze the disease spectrum， diagnostic proportion， and mutational profile of pediatric rare diseases at the First Affiliated Hospital of Henan Medical University， and to characterize their genetic features. Methods Between April 2017 and December 2024， 514 children suspected of having rare diseases and admitted to the Department of Pediatrics were enrolled. Diagnostic evaluation included serum matrix metalloproteinase-7 （MMP-7） testing， tandem mass spectrometry （MS/MS）， and high-throughput sequencing （HTS）. The disease spectrum， diagnostic yield， and genetic variation profiles of confirmed cases were systematically analyzed. Results During the study period， 70 362 children were hospitalized at the center， of whom 314 were definitively diagnosed with rare diseases， corresponding to a proportion of approximately 45/10 000 admissions. The ten most frequently diagnosed conditions accounted for 43.6% of all cases and included muscular dystrophy， retinopathy of prematurity， primary immunodeficiencies， Alport syndrome， methylmalonic acidemia， biliary atresia， mitochondrial encephalomyopathy， Wilson disease， ornithine transcarbamylase deficiency， and spinal muscular atrophy. In the top three most prevalent diseases （each comprising > 10 cases）， genetic analysis identified 125 distinct variants and 4 large genomic deletions across 30 genes. Additionally， nine cases exhibited digenic inheritance. Conclusions Neurological， metabolic-endocrine， primary immunodeficiency， and urinary system disorders constitute the predominant categories of pediatric rare diseases in this cohort. These findings highlight the necessity of strengthening early screening and standardized differential diagnosis to enhance clinical management. Notably， five cases representing disease phenotypes or genetic variants not previously reported in China were identified.

Key words: North Henan region, single center, children, rare diseases, disease spectrum