Identification of a novel splice variant in SEC23B gene in a patient with concomitant presence of congenital dyserythropoietic anemia II and Gilbert's syndrome.

BACKGROUND: Congenital dyserythropoietic anemia Ⅱ (CDA Ⅱ) is a rare inherited disorder of defective erythropoiesis caused by SEC23B gene mutation. CDA Ⅱ is often misdiagnosed as a more common type of clinically related anemia, or it remains undiagnosed due to phenotypic variability caused by the coexistence of inherited liver diseases, including Gilbert's syndrome (GS) and hereditary hemochromatosis. METHODS: We describe the case of a boy with genetically undetermined severe hemolytic anemia, hepatosplenomegaly, and gallstones whose diagnosis was achieved by targeted next generation sequencing. RESULTS: Molecular analysis revealed a maternally inherited novel intronic variant and a paternally inherited missense variant, c.[994-3C > T];[1831C > T] in the SEC23B gene, confirming diagnosis of CDA Ⅱ. cDNA analysis verified that the splice acceptor site variant results in two mutant transcripts, one with an exon 9 skip and one in which exons 9 and 10 are deleted. SEC23B mRNA levels in the patient were lower than those in healthy controls. The patient was also homozygous for the UGT1A1*6 allele, consistent with GS. CONCLUSION: Identification of the novel splice variant in this study further expands the spectrum of known SEC23B gene mutations. Molecular genetic approaches can lead to accurate diagnosis and management of CDA Ⅱ patients, particularly for those with GS coexisting.

Case Report: Infantile Cerebellar-Retinal Degeneration With Compound Heterozygous Variants in ACO2 Gene-Long-Term Follow-Up of a Sibling.

Infantile cerebellar-retinal degeneration (ICRD) is an extremely rare, infantile-onset neuro-degenerative disease, characterized by autosomal recessive inherited, global developmental delay (GDD), progressive cerebellar and cortical atrophy, and retinal degeneration. In 2012, a biallelic pathogenic variant in ACO2 gene (NM_001098.3) was found to be causative of this disease. To date, approximately 44 variants displaying various clinical features have been reported. Here, we report a case of two siblings with compound heterozygous variants in the ACO2 gene. Two siblings without perinatal problems were born to healthy non-consanguineous Korean parents. They showed GDD and seizures since infancy. Their first brain magnetic resonance imaging (MRI), electroencephalography, and metabolic workup revealed no abnormal findings. As they grew, they developed symptoms including ataxia, dysmetria, poor sitting balance, and myopia. Follow-up brain MRI findings revealed atrophy of the cerebellum and optic nerve. Through exome sequencing of both siblings and their parents, we identified the following compound heterozygous variants in the ACO2: c.85C > T (p.Arg29Trp) and c.2303C > A (p.Ala768Asp). These two variants were categorized as likely pathogenic based on ACMG/AMP guidelines. In conclusion, this case help to broaden the genetic and clinical spectrum of the ACO2 variants associated with ICRD. We have also documented the long-term clinical course and serial brain MRI findings for two patients with this extremely rare disease.

Empty Sella Syndrome Associated with Growth Hormone Deficiency: the First Case Report of Weiss-Kruszka Syndrome.

Weiss-Kruszka syndrome (WSKA), caused by heterozygous loss-of-function variants in ZNF462 gene, is a recently described and extremely rare genetic disorder. The main phenotypes include characteristic craniofacial features, ptosis, dysgenesis of the corpus callosum, and neurodevelopmental impairment. We report the first Korean boy with molecularly confirmed WSKA presenting with an atypical manifestation. A 16-year-old boy with a history of bilateral ptosis surgery presented with short stature (-3.49 standard deviation score) and delayed puberty. The patient showed characteristic craniofacial features including an inverted triangular-shaped head, exaggerated Cupid's bow, arched eyebrows, down-slanting palpebral fissures, and poorly expressive face. He had a mild degree of intellectual disability and mild hypotonia. Endocrine studies in the patient demonstrated complete growth hormone deficiency (GHD) associated with empty sella syndrome (ESS), based on a magnetic resonance imaging study for the brain that showed a flattened pituitary gland and cerebrospinal fluid space herniated into the sella turcica. To identify the genetic cause, we performed whole exome sequencing (WES). Through WES, a novel de novo heterozygous nonsense variant, c.4185del; p.(Met1396Ter) in ZNF462 was identified. This is the first case of WSKA accompanied by primary ESS associated with GHD. More clinical and functional studies are needed to elucidate this association.

Benign Convulsions with Mild Rotavirus and Norovirus Gastroenteritis: Nationwide Data from the Health Insurance Review and Assessment Service in South Korea.

There have been no large-scale studies on the epidemiology of benign convulsions with mild gastroenteritis (CwG) since the introduction of the rotavirus vaccine in South Korea in 2007. This study aimed to analyze the trends in rotavirus gastroenteritis (RVGE) and rotavirus-associated CwG (RaCwG) after rotavirus vaccination. Further, we aimed to analyze changes in norovirus gastroenteritis (NVGE) and norovirus-associated CwG (NaCwG) using nationwide data from the Korean Health Insurance Review and Assessment Service. Between 2007 and 2019, this study analyzed children aged <6 years who were diagnosed with RVGE, NVGE, RaCwG and NaCwG. The changes in the prevalence of each disease and the ratio of CwG to enteritis were analyzed and the effects of age, sex and season were also analyzed. RVGE, RaCwG, NVGE and NaCwG were diagnosed in 273,898, 4246, 35,593 and 337 patients, respectively. The prevalence of RVGE was on a decreasing trend every year, but the prevalence of NaCwG and NVGE was on an increasing trend. There was a significant annual increase in the ratio of CwG to enteritis in both viruses. In order to control the prevalence of RaCwG, measures other than the rotavirus vaccine are required and measures to prevent norovirus are necessary.

Epidemiology of Rotavirus Gastroenteritis and Rotavirus-Associated Benign Convulsions with Mild Gastroenteritis after the Introduction of Rotavirus Vaccines in South Korea: Nationwide Data from the Health Insurance Review and Assessment Service.

Using nationwide data from the Health Insurance Review and Assessment service, we assessed the impact of rotavirus vaccines, introduced in South Korea, in 2007, on changes in the prevalence of factors (age, sex, and geographic location) associated with rotavirus gastroenteritis (RVGE) and rotavirus-associated benign convulsions with mild gastroenteritis (RaCwG). We analyzed health records of children younger than 3 years who visited clinical facilities and were diagnosed with RVGE or RaCwG between 2007 and 2019. The annual mid-year population (MYP) was obtained from the Korean Statistical Information Service. The annual prevalence of RVGE, RaCwG and associated factors were statistically analyzed. Overall, 219,686, and 4032, children were confirmed to have RVGE and RaCwG, respectively. Although the annual prevalence of RVGE decreased significantly, that of RaCwG did not. The annual ratio of RaCwG to RVGE was significantly high. Compared to the prevalence of RVGE, the prevalence of RaCwG was significantly lower in rural areas. The age of RaCwG patients was significantly lower than that of the MYP and that of RVGE patients. The decrease in the number of RaCwG patients after rotavirus vaccination was not as pronounced as the decrease in the number of RVGE patients.

Ankle Arthrodesis: A Comparison of Anterior Approach and Transfibular Approach.

BACKGROUND: The purpose of this study was to compare clinical and radiological results of arthrodesis performed by the anterior approach and by the transfibular approach in ankle osteoarthritis. METHODS: Sixty patients underwent open arthrodesis (38 by the anterior approach and 22 by the transfibular approach). The visual analogue scale score and the American Orthopedic Foot and Ankle Society (AOFAS) score were examined clinically, and radiological examination was performed on the alignment of the lower extremity and bone union. RESULTS: Both groups showed significant improvement in AOFAS score (from 39.8 to 58.3 in the anterior approach group and from 44.5 to 60.7 in the transfibular approach group). There was no significant difference in AOFAS score at the last follow-up in both groups. The time to fusion was 13.5 weeks in the anterior approach group and 11.8 weeks in the transfibular approach group. Nonunion occurred in four cases in the anterior approach group and in one case in the transfibular approach group. CONCLUSIONS: Ankle arthrodesis by the anterior approach and the transfibular approach showed comparably good clinical results.

Arthroscopic Assessment of Intra-Articular Lesion after Surgery for Rotational Ankle Fracture.

BACKGROUND: The purpose of this study was to report findings of exploratory arthroscopic assessment performed in conjunction with removal of internal fixation device placed in the initial surgery for rotational ankle fracture. METHODS: A total of 53 patients (33 male, 20 female) who underwent surgery for rotational ankle fracture between November 2002 and February 2008 were retrospectively reviewed. All patients gave consent to the exploratory arthroscopic surgery for the removal of internal fixation devices placed in the initial surgery. Lauge-Hansen classification system of ankle fractures was assessed for all patients. Intra-articular lesions (osteochondral lesion, loose body, and fibrosis) were evaluated via ankle arthroscopy. Comparative analysis was then performed between radiological classification of ankle fracture/patient's symptoms and arthroscopic findings. RESULTS: Lauge-Hansen classification system of ankle fractures included supination-external rotation type (n = 35), pronation-external rotation type (n = 9), and pronation-abduction type (n = 9). A total of 33 patients exhibited symptoms of pain or discomfort while walking whereas 20 exhibited no symptoms. Arthroscopic findings included abnormal findings around the syndesmosis area (n = 35), intra-articular fibrosis (n = 51), osteochondral lesions of the talus (n = 33), loose bodies (n = 6), synovitis (n = 13), and anterior bony impingement syndrome (n = 3). Intra-articular fibrosis was seen in 31 of symptomatic patients (93.9%). Pain or discomfort with activity caused by soft tissue impingement with meniscus-like intra-articular fibrosis were found in 19 patients. There was statistical significance (p = 0.02) between symptoms (pain and discomfort) and the findings of meniscus-like fibrosis compared to the group without any symptom. CONCLUSIONS: Arthroscopic examination combined with treatment of intra-articular fibrosis arising from ankle fracture surgery may help improve surgical outcomes.

The effect of autotransfusion system in minimally invasive total knee arthroplasty.

PURPOSE: To evaluate the effect of autotransfusion system in minimally invasive total knee arthroplasty (TKA). MATERIALS AND METHODS: Seventy-one patients who underwent unilateral minimally invasive TKA between October 2009 and June 2010 were selected. The first group included 36 patients who received standard vacuum drainage and the second group, 35 patients who underwent autologous retransfusion drainage. In the first group, allogeneic blood transfusion was performed if the postoperative hemoglobin level was <7.0 g/dL or 7.0-8.0 g/dL with the presence of a medical complication and an anemic symptom. The second group received autotransfusion and allogeneic transfusion additionally according to the same criteria. Changes in the pre- and postoperative hemoglobin level, amount of auto- or allotransfusion, and frequency of allogeneic transfusion were assessed. RESULTS: Allogeneic transfusion was required in 13 patients (36.1%) in the first group and four patients (11.4%) in the second group. The mean allogeneic transfusion volume was significantly low in the second group compared to the first group (64.4 mL vs. 278.9 mL; p<0.05). The hemoglobin level on the 1st postoperative day compared to the preoperative level decreased by 22.6% in the first group and 11.7% in the second group. The postoperative hemoglobin level was higher in the second group (p<0.05). CONCLUSIONS: Minimally invasive unilateral TKA with an autotransfusion system can be beneficial in patients with no medical complications because of the decreased allogeneic transfusion.

Effect of posterior condylar offset on cruciate-retaining mobile TKA.

The objective of this article was to evaluate the effect of the change of posterior condylar offset to range of motion (ROM) and clinical results after computer-assisted cruciate-retaining mobile-bearing total knee arthroplasty (TKA). A total of 111 knees underwent cruciate-retaining mobile-bearing TKAs under computer-assisted navigation from January 2005 to September 2007. All cases were primary osteoarthritis and had <15 degrees of valgus or varus deformity. We divided patients into 4 groups according to change of posterior condylar offset, which was measured by postoperative minus preoperative posterior condylar offset (group 1: <-2 mm; group 2: -2-0 mm; group 3: 0-+2 mm; group 4: >2 mm). Preoperative age, thigh girth, body mass index, flexion contracture, further flexion, Hospital for Special Surgery (HSS) score, Knee Society (KS) knee score, and KS functional score did not show significant difference between groups. The measured change of posterior condylar offset ranged from +3.70 to -3.95 mm with a mean value of -1.67 mm. Postoperatively, there were no statistical differences between each group on flexion contracture (P=.522), further flexion (P=.442), HSS score (P=.116), KS knee score (P=.479), or KS functional score (P=.578). We could find no significant difference between ROM or clinical results with computer-assisted cruciate-retaining mobile-bearing TKAs in the comparison of groups according to changes of posterior condylar offset.