Abstract:Peroxisomal D-bifunctional protein (DBP), encoded by the
HSD17B4
gene, catalyzes β-oxidation of very long chain fatty acids (VLCFAs). The deficiency of this peroxisomal enzyme leads to the accumulation of VLCFAs, causing multisystemic manifestations including the brain, retina, adrenal gland, hearing, and skeletal system. Herein, we report the first Korean neonatal case of peroxisomal DBP deficiency and the clinical prognosis over 2 years. This patient showed craniofacial dysmorphism, cl… Show more
“…It is consistent with the literature reports that most patients with early onset had craniofacial deformities (1,(18)(19)(20). The infant had severe neonatal hypotonia and convulsions, without primitive reflex elicited on the 1st day after birth, which was consistent with the literature reports that convulsive seizures occurred within a few days after birth, generally starting on the 2nd day after birth (1,3,(18)(19)(20)(21). After the patient's family signed the informed consent form for antiepileptic drugs, a combination of antiepileptic drugs, including levetiracetam tablets, topiramate tablets, and sodium valproate oral solution, was administered successively and at the maximum dose within the safety range, but the patient still had more frequent convulsive seizures of more than 10 times a day.…”
Section: Discussionsupporting
confidence: 93%
“…In this case report, the patient showed typical clinical abnormalities including cosmetic deformities (long head deformity, high forehead, wide eye distance, high palatal arch, and talipes varus). It is consistent with the literature reports that most patients with early onset had craniofacial deformities (1,(18)(19)(20). The infant had severe neonatal hypotonia and convulsions, without primitive reflex elicited on the 1st day after birth, which was consistent with the literature reports that convulsive seizures occurred within a few days after birth, generally starting on the 2nd day after birth (1,3,(18)(19)(20)(21).…”
Section: Discussionsupporting
confidence: 91%
“…It has been reported in the literature that cranial MRI in adulthood revealed cerebellar atrophy and ataxia (23), while neonatal cranial MRI revealed no significant brain atrophy (24). Our patient's cranial MRI showed shallow sulci, local widening and deepening of the lateral fissure cistern of the right cerebral hemisphere, extensive hyperintense white matter changes in the cerebral hemisphere on T2WI, and dysplasia of the corpus callosum, which were similar to the clinical report that MRI in children with D-BDP showed different severities of lateral fissure, peripheral multiple microgyria, and delayed myelination (3,18,21).…”
Section: Discussionsupporting
confidence: 84%
“…Therefore, the lack of D-BP will indirectly lead to DHA deficiency, ultimately affecting brain and retinal development. Bae et al (18) reported that although DHA supplementation in patients could increase DHA levels, it still could not improve clinical outcomes in patients with DHA deficiency. And patients showed progressive visual impairment and brain deterioration despite early DHA supplementation (within a month) (18).…”
Section: Discussionmentioning
confidence: 99%
“…Bae et al (18) reported that although DHA supplementation in patients could increase DHA levels, it still could not improve clinical outcomes in patients with DHA deficiency. And patients showed progressive visual impairment and brain deterioration despite early DHA supplementation (within a month) (18). In addition, the disease often causes abnormal BAEP and even leads to deafness.…”
Background: D-Bifunctional protein deficiency (D-BPD) is an autosomal recessive disorder caused by peroxisomal β-oxidation defects. According to the different activities of 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase protein units, D-bifunctional protein defects can be divided into four types. The typical symptoms include hypotonia and seizures. The gene that encodes D-BP was HSD17B4, which is located in chromosome 5q23.1.Case Presentation: We report the first case of D-BPD in a Chinese patient with neonatal onset. Cosmetic malformations, severe hypotonia and seizures are prominent. The blood bile acid profile showed increased taurocholic acid, glycocholic acid, and taurochenodeoxycholic acid. Very-long-chain fatty acids (VLCFAs) revealed significant increases in hexacosanoic acid (C26:0), tetracosanoic acid/docosanoic acid (C24:0/C22:0), and hexacosanoic acid/docosanoic acid (C26:0/C22:0). Cranial MRI revealed bilateral hemispheric and callosal dysplasia, with schizencephaly in the right hemisphere. EEG showed loss of sleep–wake cycle and epileptiform discharge. Other examinations include abnormal brainstem auditory evoked potentials (BAEPs) and temporal pigmented spots on the optic disc in the right eye. After analysis by whole-exome sequencing, heterozygous c.972+1G>T in the paternal allele and c.727T>A (p.W243R) in the maternal allele were discovered. He was treated with respiratory support, formula nasogastric feeding, and antiepileptic therapy during hospitalization and died at home due to food refusal and respiratory failure at the age of 5 months.Conclusions: Whole-exome sequencing should be performed in time to confirm the diagnosis when the newborn presents hypotonia, seizures, and associated cosmetic malformations. There is still a lack of effective radical treatment. Supportive care is the main treatment, aiming at controlling symptoms of central nervous system like seizures and improving nutrition and growth. The disease has a poor outcome, and infants often die of respiratory failure within 2 years of age. In addition, heterozygous deletion variant c.972+1G>T and missense mutations c.727T>A (p.W243R) are newly discovered pathogenic variants that deserve further study.
“…It is consistent with the literature reports that most patients with early onset had craniofacial deformities (1,(18)(19)(20). The infant had severe neonatal hypotonia and convulsions, without primitive reflex elicited on the 1st day after birth, which was consistent with the literature reports that convulsive seizures occurred within a few days after birth, generally starting on the 2nd day after birth (1,3,(18)(19)(20)(21). After the patient's family signed the informed consent form for antiepileptic drugs, a combination of antiepileptic drugs, including levetiracetam tablets, topiramate tablets, and sodium valproate oral solution, was administered successively and at the maximum dose within the safety range, but the patient still had more frequent convulsive seizures of more than 10 times a day.…”
Section: Discussionsupporting
confidence: 93%
“…In this case report, the patient showed typical clinical abnormalities including cosmetic deformities (long head deformity, high forehead, wide eye distance, high palatal arch, and talipes varus). It is consistent with the literature reports that most patients with early onset had craniofacial deformities (1,(18)(19)(20). The infant had severe neonatal hypotonia and convulsions, without primitive reflex elicited on the 1st day after birth, which was consistent with the literature reports that convulsive seizures occurred within a few days after birth, generally starting on the 2nd day after birth (1,3,(18)(19)(20)(21).…”
Section: Discussionsupporting
confidence: 91%
“…It has been reported in the literature that cranial MRI in adulthood revealed cerebellar atrophy and ataxia (23), while neonatal cranial MRI revealed no significant brain atrophy (24). Our patient's cranial MRI showed shallow sulci, local widening and deepening of the lateral fissure cistern of the right cerebral hemisphere, extensive hyperintense white matter changes in the cerebral hemisphere on T2WI, and dysplasia of the corpus callosum, which were similar to the clinical report that MRI in children with D-BDP showed different severities of lateral fissure, peripheral multiple microgyria, and delayed myelination (3,18,21).…”
Section: Discussionsupporting
confidence: 84%
“…Therefore, the lack of D-BP will indirectly lead to DHA deficiency, ultimately affecting brain and retinal development. Bae et al (18) reported that although DHA supplementation in patients could increase DHA levels, it still could not improve clinical outcomes in patients with DHA deficiency. And patients showed progressive visual impairment and brain deterioration despite early DHA supplementation (within a month) (18).…”
Section: Discussionmentioning
confidence: 99%
“…Bae et al (18) reported that although DHA supplementation in patients could increase DHA levels, it still could not improve clinical outcomes in patients with DHA deficiency. And patients showed progressive visual impairment and brain deterioration despite early DHA supplementation (within a month) (18). In addition, the disease often causes abnormal BAEP and even leads to deafness.…”
Background: D-Bifunctional protein deficiency (D-BPD) is an autosomal recessive disorder caused by peroxisomal β-oxidation defects. According to the different activities of 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase protein units, D-bifunctional protein defects can be divided into four types. The typical symptoms include hypotonia and seizures. The gene that encodes D-BP was HSD17B4, which is located in chromosome 5q23.1.Case Presentation: We report the first case of D-BPD in a Chinese patient with neonatal onset. Cosmetic malformations, severe hypotonia and seizures are prominent. The blood bile acid profile showed increased taurocholic acid, glycocholic acid, and taurochenodeoxycholic acid. Very-long-chain fatty acids (VLCFAs) revealed significant increases in hexacosanoic acid (C26:0), tetracosanoic acid/docosanoic acid (C24:0/C22:0), and hexacosanoic acid/docosanoic acid (C26:0/C22:0). Cranial MRI revealed bilateral hemispheric and callosal dysplasia, with schizencephaly in the right hemisphere. EEG showed loss of sleep–wake cycle and epileptiform discharge. Other examinations include abnormal brainstem auditory evoked potentials (BAEPs) and temporal pigmented spots on the optic disc in the right eye. After analysis by whole-exome sequencing, heterozygous c.972+1G>T in the paternal allele and c.727T>A (p.W243R) in the maternal allele were discovered. He was treated with respiratory support, formula nasogastric feeding, and antiepileptic therapy during hospitalization and died at home due to food refusal and respiratory failure at the age of 5 months.Conclusions: Whole-exome sequencing should be performed in time to confirm the diagnosis when the newborn presents hypotonia, seizures, and associated cosmetic malformations. There is still a lack of effective radical treatment. Supportive care is the main treatment, aiming at controlling symptoms of central nervous system like seizures and improving nutrition and growth. The disease has a poor outcome, and infants often die of respiratory failure within 2 years of age. In addition, heterozygous deletion variant c.972+1G>T and missense mutations c.727T>A (p.W243R) are newly discovered pathogenic variants that deserve further study.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.