Novel HSD17B4 Variants Cause Progressive Leukodystrophy in Childhood: Case Report and Literature Review
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ABSTRACT:
SUBMITTER: Yamamoto A
PROVIDER: S-EPMC8512218 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC8342883 | biostudies-literature
Project description:BackgroundMitochondrial alanyl-tRNA synthetase 2 gene (AARS2) related disease is a rare genetic disorder affecting mitochondrial metabolism, leading to severe cardiac disease in infants or progressive leukodystrophy in young adults. The disease is considered ultra-rare with only 39 cases of AARS2-leukodystrophy previously reported.Case presentationWe present the case of a young man of consanguineous heritage suffering from cognitive decline and progressive spasticity as well as weakness of the proximal musculature. Utilizing MRI and whole genome sequencing, the patient was diagnosed with a homozygous AARS2 missense variant (NM_020745.3:c.650C > T; p.(Pro217Leu)) and a homozygous CAPN3 variant (NM_000070.2: c.1469G > A; p.(Arg490Gln)), both variants have previously been identified in patients suffering from AARS2 related leukodystrophy and limb-girdle muscular dystrophy, respectively.ConclusionsThis case report presents a case of homozygous AARS2 leukodystrophy and serves to highlight the importance of whole genome sequencing in diagnosing rare neurological diseases as well as to add to the awareness of adult onset leukodystrophies.
| S-EPMC8280508 | biostudies-literature
Project description:We report a case of a 55 years old women who present a ALK associated renal cell carcinoma, with 3p deletion and measling of TFE3 expression. With CGH analysis and FISH we identify the rearrangment of ALK with TPM3
2017-03-24 | GSE96980 | GEO
Project description:Introduction: O'Donnell-Luria-Rodan syndrome was recently identified as an autosomal dominant systemic disorder caused by variants in KMT2E. It is characterized by global developmental delay, some patients also exhibit autism, seizures, hypotonia, and/or feeding difficulties. Methods: Whole-exome sequencing of family trios were performed for two independent children with unexplained recurrent seizures and developmental delay. Both cases were identified as having de novo variants in KMT2E. We also collected and summarized the clinical data and diagnosed them with O'Donnell-Luria-Rodan syndrome. Structural-prediction programs were used to draw the variants' locations. Results: A 186 G>A synonymous variant [NM_182931.3:exon4: c.186G>A (p.Ala62=)] was found in one family, resulting in alternative splicing acid. A 5417 C>T transition variant [NM_182931.3:exon27: c.5417C>T (p.Pro1806Leu)] was found in another family, resulting in 1806 Pro-to-Leu substitution. Both variants were classified as likely pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines and verified by Sanger sequencing. Conclusion: To date, three studies of O'Donnell-Luria-Rodan syndrome have been reported with heterogeneous clinical manifestations. As a newly recognized inherited systemic disorder, O'Donnell-Luria-Rodan syndrome needs to be paid more attention, especially in gene testing.
| S-EPMC7935518 | biostudies-literature
Project description:BACKGROUND:TAFRO syndrome is a systemic inflammatory disorder that manifests as thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Renal dysfunction is frequently complicated with TAFRO syndrome, however, it is challenging to perform kidney biopsy in patients with TAFRO syndrome in the presence of thrombocytopenia. Renal histology in TAFRO syndrome mainly shows membranoproliferative glomerulonephritis (MPGN)-like lesions or thrombotic microangiopathy (TMA)-like glomerulopathy. We review our case and previous reports of TAFRO syndrome with kidney biopsy findings and discuss the renal pathophysiology of TAFRO syndrome. CASE PRESENTATION:We describe a previously healthy 48- year-old woman with TAFRO syndrome. Kidney biopsy performed before the treatment showed diffuse global endocapillary proliferative changes with endothelial cell swelling, double contours of partial capillary walls, and mesangiolysis, consistent with TMA-like glomerulopathy. Glucocorticoid therapy including steroid pulse was ineffective and she developed anasarca, renal dysfunction and oliguria. Hemodialysis was required. However, the anti-Interleukin (IL)-6 receptor antibody (tocilizumab) therapy was very effective. An increase in urinary volume was achieved about 2 weeks after the tocilizumab therapy and hemodialysis was discontinued. To investigate the renal pathophysiology of TAFRO syndrome, we performed immunohistological staining of vascular endothelial growth factor (VEGF)-A, CD34, and D2-40, in our case and a normal control kidney. Glomerular VEGF-A was especially positive in podocytes both, in the control and in the case, with no significant difference and there was a significant increase of VEGF-A staining area in the cortical peritubular capillaries in the case. Both glomerular and renal cortical CD34 expression were significantly decreased in our case. D2-40 expression in cortex was not significantly different. CONCLUSIONS:We reviewed our case and other 10 previous reports about renal biopsy findings in TAFRO syndrome and found that glomerular microangiopathy was a common finding. IL-6-VEGF-axis-induced glomerular microangiopathy may play a crucial role in developing acute kidney injury in TAFRO syndrome and the anti-IL-6 receptor antibody therapy may be useful for TAFRO syndrome refractory to glucocorticoids. About the pathophysiology of VEGF in TAFRO syndrome, VEGF balance in the glomerulus and perhaps in the peritubular capillary system as well may be critical. Further investigation is needed.
| S-EPMC6798393 | biostudies-literature
Project description:BackgroundProgressive nodular histiocytosis (PNH) is a rare, clinically distinct non-Langerhans cell histiocytic neoplasm affecting the skin and mucous membranes with no signs of spontaneous regression of the lesions. Patients typically have hundreds of lesions of superficial xanthomatous papules to nodules and deep larger fibrous nodules, which can be life-threatening if laryngeal mucosa was involved. So far, few cases of PNH have been reported and no effective treatment has been shown to reverse the progressive clinical course.Case presentationHere we describe a case of PNH presenting as diffuse, progressively enlarging papules, nodules and even leonine appearance in a young woman. The diagnosis was confirmed by histological and immunohistochemical findings. Next-generation sequencing (NGS) showed identical missense mutation in XIAP Y404C and in-frame deletion in MAPK1 A2[6>5]. Since ERK inhibitor has not been on the market yet, the patient received chemotherapy instead. Traditional chemotherapy with intermediate-dose of cytarabine (500 mg/m2 cytarabine by 3-hour infusion every 12 hours for 3 days every 5 weeks) achieved favorable therapeutic effect as confirmed by clinical symptoms and PET/CT imaging.ConclusionsPNH is a rare, proliferative disorder with disfiguring lesions and deteriorative quality of life. Mutations in MAPK1, XIAP may play crucial roles in the pathogenesis of PNH. Intermediate-dose cytarabine can be considered as a promising treatment option for PNH patients.
| S-EPMC8430172 | biostudies-literature
Project description:Intestinal malformations are common disorders in newborn and favorable outcomes have been reported for such conditions. Although, if the patient is treated in a not experienced center, misinterpretation of the clinical and radiological findings may lead to errors in treatment and possible complications in adulthood. We report a case of a congenital megaduodenum which was misinterpreted as an intestinal malrotation resulting in late complications. The patient underwent a successful surgical resection of the duodenum with improvement of his clinical symptoms and nutritional status. This case report emphasizes the importance of considering megaduodenum in the differential diagnosis of patients with feeding impairment, even during adulthood. Early diagnosis and treatment may improve patients' outcome and reduce morbidity.
| S-EPMC6514750 | biostudies-literature
Project description:We present cases of sewing needle as a nidus of the bladder stone in a seven-year-old girl admitted to the hospital with chief complaining burning micturition for 6 months. The Kidney, Ureter, and Bladder (KUB) X-ray revealed the bladder stone was 3.5?cm in length at the pelvic cavity and sewing needle in its center. The bladder stone was removed by open cystolithotomy without any complications.
| S-EPMC6928317 | biostudies-literature
Project description:Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare, benign clinical entity of unknown cause. RDD is characterised by the overproduction and accumulation of histiocytes, primarily in the lymph nodes, although it may affect every organ and system. It predominantly affects children and young adults. Typically, patients are in good general condition, with massive cervical lymphadenopathy and fever. In about 40% of cases extranodal localisation of RDD is diagnosed. In laboratory tests the most common abnormalities are increased erythrocyte sedimentation rate (ESR), leukocytosis with neutrophilia, normocytic anaemia, and hypergammaglobulinaemia. Histopathological examination remains the mainstay of diagnosis - lymph nodes have massive sinusoidal dilation, containing histiocytes positive for S-100 and CD68, and negative for CD1a. Most patients do not require treatment as spontaneous remissions are observed. We present a brief review of the literature and the case of a six-year-old boy with cervical lymphadenopathy diagnosed with RDD. So far, the patient has not required systemic treatment and has been kept under observation.
| S-EPMC6305605 | biostudies-other
Project description:Objective: The aim of the present study is to explore the clinical and genetic characteristics of 3p deletion syndrome to improve clinicians' understanding of the disease. Methods: The clinical manifestations, process of diagnosis and treatment, and genetic characteristics of an individual case of 3p deletion syndrome were analyzed. CNKI, Wanfang Data, and the Biomedical Literature Database (PubMed) were searched. The search time limit, using "3p deletion syndrome" and "BRPF1" as keywords, was from the creation of the database up to June 2020. Related data were reviewed. Results: The proband was a male child with general developmental and intellectual disabilities, special facial features and congenital heart disease. The child was the parents' first pregnancy and first born. Gene microarray analysis showed a 10.095 Mb deletion in the 3p26.3-p25.3 region, resulting in a heterozygous mutation of the BRPF1 gene; thus, the patient was diagnosed with 3p deletion syndrome. At the time of diagnosis, the child was 1 year of age and was responding to comprehensive rehabilitation training. A total of 29 well-documented cases were found in the literature, of which 19 cases had an onset within 1 year of birth, and mainly manifested with mental and motor development disabilities and abnormal facial features, with different gene deletions, depending on the size and location of the 3p deletion. Conclusion: The genetic test results of the child in this study indicated a heterozygous deletion of the BRPF1 gene on the short arm of chromosome 3, which was a unique feature of this study, since it was rarely mentioned in other reports of 3p deletion syndrome. The clinical phenotype of this syndrome is complex as it can include intellectual and motor development backwardness, low muscle tone, certain abnormal facial features (low hairline, bilateral ptosis, widely spaced eyes, a forward nose, left ear auricle deformity, a high-arched palate, a small jaw), and the deformation of systems such as the gastrointestinal tract and the urinary tract malformation or symptoms of epilepsy. As clinical manifestations can be relatively mild, the syndrome is easy to miss or misdiagnose. Clinical workers need to be aware of this disease when they find that children have special features, such as stunted growth, low muscle tone or ptosis, and it needs to be diagnosed through genetic testing. Most children are able to develop certain social skills after rehabilitation treatment.
| S-EPMC7902511 | biostudies-literature