ABSTRACT
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.