RESUMO
Objective:To summarize the clinical characteristics and genetic etiology of infants with D-bifunctional protein deficiency (DBPD).Methods:This study involved two DBPD newborns who were hospitalized in the Second Affiliated Hospital of Wenzhou Medical University in August 2020 and November 2020. Clinical data including manifestations, radiographic findings and genetic testing results were retrospectively analyzed. Relevant articles up to November 2022 were retrieved from various databases including CNKI, Wanfang, CQVIP, Online Mendelian Inheritance in Man and PubMed using the terms of "D-bifunctional protein deficiency" and " HSD17B4" in both Chinese and English. Clinical data of the cases diagnosed with DBPD by genetic testing within two years of age were collected. Clinical features and genetic etiology of the children with DBPD were summarized by descriptive statistical analysis. Results:Both neonates in this report presented with dyspnea, hypotonia, intractable epilepsy, poor response, absence of primitive reflexes, and craniofacial malformation. Whole-exome sequencing revealed that patient 1 carried heterozygous variations of c.972+1G>T and c.727T>A (p.W243R) in the HSD17B4 gene, which were inherited from his father and mother, respectively. A homozygous variation of c.1333+4A>G in the HSD17B4 gene was identified in patient 2. All these mutations were pathogenic. Thirteen papers (12 in English and one in Chinese) involving 19 patients from 16 pedigrees were retrieved. Altogether 21 patients (eight males and 13 females) were included, and among them, four from two pedigrees were born to consanguineous parents. There were 21 patients with hypotonia, 20 with epileptic seizures (17 presenting with epileptic seizures within 5 d after birth) and 12 with craniofacial deformities including high forehead, long philtrum and high palatine arches. Genetic tests showed that 13 patients carried compound heterozygous variations in the HSD17B4 gene and eight patients had homozygous variations. Twenty-six variations in the HSD17B4 gene were detected, including 16 missense mutations, seven splicing mutations, two nonsense mutations and one frameshift mutation. Conclusion:DBPD should be considered and genetic tests should be given when newborns have dystonia and intractable epilepsy complicated by appearance deformity.