Dopa-responsive dystonia with additional unusual clinical features: A case report confirmed by molecular genetics

The term dopa-responsive dystonia (DRD) is used to describe a group of neurometabolic disorders, which are characterized by dystonia, and are typically associated with diurnal fluctuations and respond to levodopa treatment. Autosomal dominant DRD (DYT5a, MIM# 128230) is caused by a heterozygous mutation in the GTP cyclohydrolase 1 (GCH1) gene (MIM# 600225). GCH1 encodes an enzyme, which is involved in the biosynthesis of tetrahydrobiopterin, an essential co-factor for tyrosine hydroxylase. Herein, we report the case of a 16-year-old girl who was diagnosed with DYT5a. She exhibited additional unusual clinical features, including intellectual disability, depression, multiple skeletal anomalies, and short stature, which are not commonly observed in patients with DYT5a. The patient harbored a heterozygous missense variant, c.539A>C, p.Gln180Pro, in the GCH1 gene, which was identified by targeted gene panel analysis using next-generation sequencing.

Nonclassic congenital lipoid adrenal hyperplasia diagnosed at 17 months in a Korean boy with normal male genitalia: emphasis on pigmentation as a diagnostic clue

Congenital lipoid adrenal hyperplasia (CLAH) is one of the most fatal conditions caused by an abnormality of adrenal and gonadal steroidogenesis. CLAH results from loss-of-function mutations of the steroidogenic acute regulatory (STAR) gene; the disease manifests with electrolyte imbalances and hyperpigmentation in neonates or young infants due to adrenocortical hormone deficiencies, and 46, XY genetic male CLAH patients can be phenotypically female. Meanwhile, some patients with STAR mutations develop hyperpigmentation and mild signs of adrenal insufficiency, such as hypoglycemia, after infancy. These patients are classified as having nonclassic CLAH (NCCLAH) caused by STAR mutations that retain partial activity of STAR. We present the case of a Korean boy with normal genitalia who was diagnosed with NCCLAH. He presented with whole-body hyperpigmentation and electrolyte abnormalities, which were noted at the age of 17 months after an episode of sepsis with peritonitis. The compound heterozygous mutations p.Gly221Ser and c.653C>T in STAR were identified by targeted gene-panel sequencing. Skin hyperpigmentation should be considered an important clue for diagnosing NCCLAH.

Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%). Among the LQTS-related genes, we detected a previously reported pathogenic variant, CACNA1C c.1552C>T, responsible for cardiac-only Timothy syndrome. Among the genes related to other cardiac diseases, a likely pathogenic variant, RYR2 c.11995A>G, was identified in a patient with catecholaminergic polymorphic ventricular tachycardia. Another patient who developed dilated cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy. Comprehensive screening of genetic variants using multigene panel sequencing enables detection of genetic variants with a possible involvement in QTc interval prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.

Development of a Poikilocyte Measuring Method Using Image Analysis Software

BACKGROUND: To achieve consistency in poikilocytes grading in peripheral blood cell examinations, we made an image-based differential count (IDC) software to measure the degree of abnormalities in individual red blood cells (RBCs) and relative fractions of poikilocytes. METHODS: Thirty peripheral blood samples were analyzed. Smear slides were examined on a microscope with charge-coupled device (CCD) camera. To verify this program, we compared the IDC results with the results of manual differential counting (MDC). Relative fractions of schistocytes, echinocytes, and elliptocytes were measured by IDC and MDC. The error rate of IDC was measured by confirming the final processed images of IDC. Correlations of IDC and MDC results were compared using linear regression analysis and the time required for each test was measured. For presentation of the mathematical decision criteria of poikilocytes, IDC algorithms for recognizing schistocytes, echinocytes, and elliptocytes were made using simple geometrical or mathematical formulas. RESULTS: The error rate of IDC was 2.8%. For analysis of 1,000 RBCs, MDC took 7.3 minutes and IDC took 2.7 minutes. Linear regression coefficients were 0.776 (P<0.001) for schistocytes, 0.895 (P<0.001) for echinocytes, and 1.001 (P<0.001) for elliptocytes. CONCLUSIONS: It was possible to define poikilocytes with geometrical or mathematical formulas using image analysis programs. The IDC program would be helpful for consistent grading of poikilocytes.

A Preliminary Study for Applying Antiperinuclear Antibody Test to 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis

BACKGROUND: The American College of Rheumatology/European League against Rheumatism classification criteria for rheumatoid arthritis (ACR/EULAR criteria) include the rheumatoid factor (RF) test and the anti-citrullinated peptide/protein antibody (ACPA) test as serologic makers for rheumatoid arthritis. Antiperinuclear factor (APF) test, an originator of ACPA, is highly specific for rheumatoid arthritis and can be detected in RF or anti-cyclic citrullinated peptide (anti-CCP) negative rheumatoid arthritis, but it is not included in the serologic criterion of ACR/EULAR criteria. In this study, we investigated the way for applying the APF test to ACR/EULAR criteria. METHODS: We analyzed clinical symptoms and laboratory findings of 53 patients who were suspected having rheumatoid arthritis. All patients were negative for the RF and anti-CCP and positive for APF. We classified these patients into 4 groups according to the fluorescence intensity of APF test, and gave 1-4 points for APF positivity. The proportion of patients who scored 6 or greater in ACR/EULAR criteria in relation to APF scores was evaluated. RESULTS: Median scores of ACR/EULAR criteria showed a tendency to increase as the level of fluorescence intensity of APF rises, but ACR/EULAR scores of 4 groups were not different significantly from each other (P>0.05). The proportion of patients who scored 6 or greater in ACR/EULAR criteria were 39.6% and 77.4%, when scores of APF positivity were 2 and 3 points, respectively. CONCLUSIONS: We think it is reasonable to include APF test in the ACPA of ACR/EULAR criteria and give 3 points for APF positivity, regardless of its fluorescence intensity.

Ventriculostomy-Associated Infection : Analysis of Risk Factors and the Venue of External Ventricular Drainage / 대한뇌혈관외과학회지

OBJECTIVE: The purpose of this study is to evaluate the risk factors for ventriculostomy-associated infections (VAI) and to examine the differences among VAI according to the venue of catheter placement in our institute. Materials and METHODS: During a four-year period, 114 patients of the neurosurgical intensive care unit (NICU) who received an external ventricular drainage (EVD), were retrospectively studied. The use of prophylactic systemic antibiotics was not included in the evaluation of the risk factors for VAI, because this was applied to all patients in our trial. RESULTS: One hundred sixty-five catheters were placed, in 114 patients, among whom 7.9% developed ventriculitis. The risk of VAI was not significantly associated with age, intial Glasgow coma scale (GCS) score, indication for the catheter, craniotomy, duration of catheter, DM, hypertension and repeated catheter insertion. Furthermore, EVD catheterization in non-operating places was not associated with a trend toward higher VAI as well. CONCLUSION: Risk factors for an increased incidence of VAI were not observed in our trials. In our study, the risk of VAI was not associated with the venue of catheter placement. These findings suggest that EVD catheter insertion in non-operating places may be a safe procedure without the risk of VAI.

DEXA T-score Concordance and Discordance Between hip and Lumbar Spine / 대한척추외과학회지

OBJECTIVE: To evaluate the concordance, or discordance, of the osteoporotic diagnosis between femur neck and lumbar spine, using DEXA T-scores and the WHO classification. MATERIALS AND METHODS: The BMD (Define?) on both hips and of the lumbar spine of 718 Korean females were measured. The mean age of the subjects was 55.5 years (31-91). The BMD data were obtained from 3 hip regions and from the lumbar spine, anteroposteriorly, using dual-energy x-ray absorptiometry (Lunar). The BMDs of femur neck and the L2-4 vertebrae were classified into normal (a T-score >-1), osteopenia (-1 < or = T-score < -2.5) and osteoporosis (-2.5< or =T-score) using the WHO definitions. RESULTS: There was significant correlation between the femur neck and lumbar BMDs (r=0.772). However, the discordance rate was 33% for all the cases, but this was 20% in the subjects below 50 of age, 31% in the subjects in their 50's, 47% in their 60's and 42% when 70 or above. The discordance rates of the normal, osteopenic and osteoporotic groups were 21, 54 and 17% respectively, with the highest discordance rate in the osteopenia group. Among the 649 persons in the normal or osteopenia groups, in relation to the femur neck BMD, there were 67 (10.3%) in the osteoporotic group with L2-4 BMD. But the reverse situation was only 12 persons from 594 (2.0%). (Eds note: this whole section makes little sense? What were the BMDs? The last sentence is completely meaningless.) CONCLUSIONS: The discordance rate between the femur neck and lumbar spine was as high as 33%, and was the highest in the osteopenia persons in their 60's. Therefore, in these persons the BMD of both sites should be checked together, but if not, the lumbar BMD should be checked first.

The Influence of Androgen Deficiency and Osteopenia on Fracture Healing in Orchiectomized Rats / 대한정형외과학회잡지

PURPOSE: The purpose of this study was to evaluate the effect of testosterone deficiency and osteopenia on fracture healing using orchiectomized adult rats. MATERIALS AND METHODS: Fifty-two 3 month old male rats were used. Animals were divided into 3 groups. Group 1 received sham operations and groups 2 and 3 were orchiectomized. At 4 weeks, right tibial shaft fractures were administered in all animals. Afterwards in group 3, testosterone was injected intra-peritoneally for 4 weeks. After 8 weeks of breeding, animals were sacrified for morphometrical, histopathological and biomechanical testing. RESULTS: No nonunion or delayed union was observed. Differences in tibial volumes and circumferences between the fracture site and the corresponding contralateral site were less in groups 2 and 3 than in group 1, with statistical significance. The yield strength and the trabecular area of the fractured tibiae were significantly lower in group 2, but group 3 and group 1 were similar. CONCLUSION: Even though there was no evidence of compromised fracture healing, both of the androgen deficiency and osteopenia induced by orchiectomy negatively influenced callus volume and strength. But osteopenia did not influece callus strength. The above results demonstrate the positive effect of testosterone injection on fracture healing.