Nusinersen for Spinal Muscular Atrophy Type I with Chronic Respiratory Failure: A Retrospective Study in South Korea

Purpose@#To analyze the efficacy and safety of nusinersen in patients with spinal muscular atrophy (SMA) type I with chronic respiratory failure. @*Materials and Methods@#We retrospectively reviewed seven patients diagnosed with SMA type I and chronic respiratory failure who were on permanent ventilation and treated with nusinersen at Gangnam Severance Hospital between January 2018 and July 2023. Patient demographics and clinical characteristics were recorded, and treatment progress was evaluated according to Hammersmith Infant Neurological Examination (HINE-2) and Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores. @*Results@#Patients initially developed hypotonia at a mean age of 3.7 months. Mean age at start of nusinersen was 7.3 years; the mean duration of follow-up after starting nusinersen was 46.2 months. At 6-, 18-, 38-, 58-, and 74-month follow-up, the mean changes in CHOP-INTEND scores were 1.0, 2.9, 1.8, 1.5, and 1.5, respectively, and the proportions of patients who showed disease amelioration were 28.6%, 71.4%, 75.0%, 100%, and 100%, respectively. @*Conclusion@#Nusinersen is safe and effective in patients with SMA type I, even those with chronic respiratory failure and those on permanent ventilation. No significant adverse effects of nusinersen were observed.

A female patient with Xp21 gene deletion syndrome

Xp21 contiguous gene deletion syndrome is associated with complex glycerol kinase deficiency, congenital adrenal hypoplasia, Duchene muscular dystrophy, and intellectual disability. Xp21 gene deletion syndrome is X-linked recessive, so most symptomatic patients are male, and only a few female symptomatic patients have been reported. We report the first female Korean case of an Xp21 deletion. NGS data were analyzed for copy number variation, and the Xp21 deletion (chr X:29301056-31838200) was confirmed using real-time PCR.

Genotype-phenotype correlations in pediatric patients with myotonic dystrophy type 1 / 소아과

PURPOSE: Myotonic dystrophy, also known as dystrophia myotonica (DM), is an autosomal dominant disorder with 2 genetically distinct forms. DM type 1 (DM1) is the more common form and is caused by abnormal expansion of cytosine/thymine/guanine (CTG) repeats in the DM protein kinase (DMPK) gene. Our study aimed to determine whether the age of onset is correlated with CTG repeat length in a population of pediatric patients with DM1. METHODS: We retrospectively identified 30 pediatric patients with DM1 that underwent DMPK testing, of which the clinical data of 17 was sufficient. The cohort was divided into 2 subgroups based on the clinical phenotype (congenital-onset vs. late-onset) and number of CTG repeats ( < 1,000 vs. ≥1,000). RESULTS: We found no significant difference between the age of onset and CTG repeat length in our pediatric patient population. Based on clinical subgrouping, we found that the congenital-onset subgroup was statistically different with respect to several variables, including prematurity, rate of admission to neonatal intensive care unit, need for respiratory support at birth, hypotonia, dysphagia, ventilator dependence, and functional status on last visit, compared to the late-onset subgroup. Based on genetic subgrouping, we found a single variable (poor feeding in neonate) that was significantly different in the large CTG subgroup than that in the small CTG subgroup. CONCLUSION: Clinical variables exhibiting statistically significant differences between the subgroups should be focused on prognosis and designing tailored management approaches for the patients; our findings will contribute to achieve this important goal for treating patients with DM1.

Ophthalmoplegia in Mitochondrial Disease

PURPOSE: To evaluate the classification, diagnosis, and natural course of ophthalmoplegia associated with mitochondrial disease. MATERIALS AND METHODS: Among 372 patients with mitochondrial disease who visited our hospital between January 2006 and January 2016, 21 patients with ophthalmoplegia were retrospectively identified. Inclusion criteria included onset before 20 years of age, pigmentary retinopathy, and cardiac involvement. The 16 patients who were finally included in the study were divided into three groups according to disease type: Kearns-Sayre syndrome (KSS), KSS-like, and chronic progressive external ophthalmoplegia (CPEO). RESULTS: The prevalences of clinical findings were as follows: ptosis and retinopathy, both over 80%; myopathy, including extraocular muscles, 75%; lactic acidosis, 71%; and elevated levels of serum creatine kinase, 47%. Half of the patients had normal magnetic resonance imaging findings. A biochemical enzyme assay revealed mitochondrial respiratory chain complex I defect as the most common (50%). The prevalence of abnormal muscle findings in light or electron microscopic examinations was 50% each, while that of large-scale mitochondrial DNA (mtDNA) deletions in a gene study was 25%. We compared the KSS and KSS-like groups with the CPEO patient group, which showed pigmentary retinopathy (p < 0.001), cardiac conduction disease (p=0.013), and large-scale mtDNA deletions (p=0.038). KSS and KSS-like groups also had gastrointestinal tract disorders such as abnormal gastrointestinal motility (p=0.013) unlike the CPEO group. CONCLUSION: Patients with KSS had gastrointestinal symptoms, which may indicate another aspect of systemic involvement. The presence of large-scale mtDNA deletions was an objective diagnostic factor for KSS and a gene study may be helpful for evaluating patients with KSS.

Age-Based Characteristics of West Syndrome in Patients with Mitochondrial Disease / 대한소아신경학회지

PURPOSE: West syndrome is a severe form of age-specific epilepsy that typically affects infants younger than 2 years of age with mitochondrial disease. We aimed to examine age-specific characteristics of the syndrome in these patients. METHODS: We retrospectively analyzed 54 patients with West syndrome diagnosed with mitochondrial disease between March 2006 and March 2016. We compared treatment strategies and diagnostic and clinical variables between patients with early-onset ( < 6 months of age) and late-onset (≥6 months of age) seizures. RESULTS: Seizure was the first symptom in 30 (90.9%) and 13 (65%) patients of the early-onset and late-onset groups, respectively (P=0.046). Delayed development was observed in 3 (9.1%) and 7 (35%) patients of the early-onset and late-onset groups, respectively (P=0.023). Lactate levels were normal in 17 patients (55%) of the early-onset group and 5 (25%) of the late-onset group (P=0.036), while initial brain magnetic resonance imaging (MRI) findings were normal in 23 (67.6%) and 8 (40%) patients of the early-onset and late-onset groups, respectively. Final MRI findings were abnormal in 32 patients (94.1%) of the early-onset group and 18 (90%) of the late-onset group (P=0.036). Although ketogenic diets reduced seizure frequency in both groups, the difference was not significant. CONCLUSION: There is no significant difference in epilepsy-related variables when patients are divided based on a cut-off age of 6 months. However, differences in the first symptom at onset and MRI findings were observed. Although lactate levels were not of significant diagnostic value in the early-onset group, they may be in the late-onset group.

Successful removal of a foreign body by endoscopic balloon dilatation at the colonic stricture / 영남의대학술지

Most ingested foreign bodies pass readily throughout intestinal tract if they reach the stomach. In some cases, foreign bodies may be impacted behind a luminal constriction but are rare in colon. Here, we report the case of a 59-year-old man who did laparoscopic anterior resection due to sigmoid colon cancer 2 years ago and ischemic colitis was repeated on the anastomosis site. He initially presented with symptoms of abdominal pain 3 months before and melena 1 day before admission. Abdomen computerized tomography showed a 3.2 cm segment of luminal narrowing of the proximal colon involving upstream foreign material stasis. Sigmoidoscopic approaches revealed near complete obstruction on the anal verge of 20 cm and scope passing failed. Balloon dilatations were done on the obstruction site four times all and a foreign body impacted above the obstruction site was removed by an alligator without any complications. The foreign body removed looks like plastic or a shell, about 20 mm in size.

The Clinical Significance of Serum Ferritin in Pediatric Non-Alcoholic Fatty Liver Disease / 대한소아소화기영양학회지

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) in children has become an important public health issue because of its high prevalence and severity. Several noninvasive methods for estimating NAFLD are under investigation. We aimed to evaluate the usefulness of serum ferritin as a biomarker of severity of pediatric NAFLD patients. METHODS: A total of 64 NAFLD patient were enrolled from Severance Children's Hospital from March 2010 to February 2013. Serum ferritin levels, liver related laboratory tests, liver magnetic resonance imaging (MRI) (2-dimensional [2D] proton density-fat fraction) and NAFLD severity markers were compared between obese group and overweight group. Correlation analyses were performed between serum ferritin and laboratory values including NAFLD severity markers. RESULTS: In obese group, serum ferritin, alanine aminotransferase (ALT), total bilirubin, international normalized ratio (INR), MRI 2D proton density-fat fraction, aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis-4 (FIB-4) (an index score calculated from platelet count, ALT, AST and age) were significantly higher than those of overweight group. NAFLD severity markers, APRI and FIB-4, and liver specific important laboratory values, AST, ALT, INR, cholesterol, triglyceride and low density lipoprotein show significant correlation with serum ferritin in NAFLD patients. CONCLUSION: Serum ferritin concentrations could be a candidate of useful severity marker in the pediatric NAFLD patients.

Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension

BACKGROUND/AIMS: Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. METHODS: Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. RESULTS: The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. CONCLUSIONS: The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.

Tolosa-Hunt Syndrome in a Child

Tolosa-Hunt syndrome is a rare disease caused by non-specific inflammation of the cavernous sinus, superior orbital fissure and the apex of the orbit. It is characterized by ophthalmoplegia, unilateral headache or periorbital pain. Brain magnetic resonance imaging (MRI) usually shows an inflammation of cavernous sinus. It is known that steroid pulse therapy is effective. In this case, we diagnosed a 12-year-old female with Tolosa-Hunt syndrome suffered from left ophthalmoplegia and left sided headache. Her Brain MRI showed mild enlargement of left cavernous sinus. After methylprednisolone pulse therapy and following dexamethasone treatment, her symptoms were markedly improved. In children who suffer from periorbiral pain and ophthalmoplegia, proper brain MRI could be helpful in differential diagnosis including Tolosa-Hunt syndrome.

A Case of Acute Renal Failure Associated with Non-fulminant Acute Hepatitis A / 영남의대학술지

Acute hepatitis A is a generally self-limiting disease of the liver. Acute renal failure is rare in patients with acute non-fulminant hepatitis A. Acute tubular necrosis is the most common form of renal injury found in such patients. The 36 years old male patient visited our hospital with complaint of general weakness, fatigue, nausea, vomiting and myalgia. He was diagnosed with acute renal failure associated with acute non-fulminant hepatitis A. We report here on a case of acute renal failure associated with non-fulminant hepatitis A, and we include a review of the literature.

Apical Hypertrophic Cardiomyopathy with Apical Aneurysm and Thrombus Diagnosed by Contrast Echocardiography / 영남의대학술지

Apical hypertrophic cardiomyopathy is rare disease and a variant of hypertrophic cardiomyopathy with prevalence of 1 in 500 in the general population. Apical hypertrophic cardiomyopathy with apical aneurysm and intramural thrombus is extremely rare. We report a case of apical hypertrophic cardiomyopathy progressing to left ventricular apical aneurysm with intramural thrombus diagnosed by contrast echocardiography.

A Case of Exit-Site Infection and Abscess by Mycobacterium Abscessus in a CAPD Patient / 영남의대학술지

Nontuberculous mycobacterial infections are a rare, but clinically important cause of infections in continuous ambulatory peritoneal dialysis (CAPD) patients. This is typically suspected when a patient does not respond to treatment with the usual antibiotics. We describe here a case of Mycobacterium abscessus exit site infection with abdominal wall abscess formation that was associated with CAPD, which required peritoneal catheter removal, surgical debridement of the abscess and long term antibiotic therapy.