Is increased Mean platelet volume associated with neurologic outcome after non-traumatic subarachnoid hemorrhage?

Objective@#This study evaluated the clinical usefulness of mean platelet volume (MPV) for predicting functional outcomes in subarachnoid hemorrhage (SAH) patients. @*Methods@#This is a retrospective analysis of patients who were diagnosed with SAH in the emergency room. Based on their modified Rankin Scale (mRS) score, patients were divided into two groups: 0-2 (good outcome) and 3-6 (poor outcome). Univariable and multivariable analyses were performed to investigate whether MPV, along with other multiple factors, was associated with poor prognosis. Receiver operating characteristic (ROC) curve analysis was performed to determine the value of MPV as a predicting factor of neurological prognosis. Compared to other factors, Hunt Hess grade (HHG) and modified Fisher grade (mFG) considerably influenced the outcomes in both groups (Model 1; model including all factors). Hence, a new model (Model 2) was constructed, comprising multiple factors excluding these two factors. @*Results@#A total of 143 patients were included in this study. Although MPV was different between the two groups, it was not a significant factor in Model 1 in the multivariable analysis. In Model 2, MPV (odds ration [OR], 1.71; 95% confidence interval [CI], 1.05-2.8), age (OR, 1.06; 95% CI, 1.03-1.1), and surgical treatment (OR, 0.37; 95% CI, 0.15-0.87) were significant factors related to poor outcomes. Area under the curve (AUC) of Model 1 was 0.93, 0.85 in HHG; 0.78 in Model 2, 0.65 in mFG, and 0.62 in MPV. @*Conclusion@#Although MPV differed significantly between the good and poor outcome groups, it is insufficient to predict poor outcomes in SAH patients as an independent biomarker.

Prospective evaluation of the clinical utility of whole-exome sequencing using buccal swabbing for undiagnosed rare diseases

Purpose@#Whole-exome sequencing (WES) has been a useful tool for novel gene discovery of various disease categories, further increasing the diagnostic yield. This study aimed to investigate the clinical utility of WES prospectively in undiagnosed genetic diseases. @*Materials and Methods@#WES tests were performed on 110 patients (age range, 0-28 years) with suspected rare genetic diseases. WES tests were performed at a single reference laboratory and the variants reported were reviewed by clinical geneticists, pediatricians, neurologists, and laboratory physicians. @*Results@#The patients’ symptoms varied with abnormalities in the head or neck, including facial dysmorphism, being the most common, identified in 85.4% of patients, followed by abnormalities in the nervous system (83.6%). The average number of systems manifesting phenotypic abnormalities per patient was 3.9±1.7. The age at presentation was 2.1±2.7 years old (range, 0-15 years), and the age at WES testing was 6.7±5.3 years (range, 0-28 years). In total, WES test reported 100 pathogenic/likely pathogenic variants or variants of uncertain significance for 79 out of 110 probands (71.8%). Of the 79 patients with positive or inconclusive calls, 55 (50.0%) patients were determined to have good genotype-phenotype correlations after careful review. Further clinical reassessment and family member testing determined 45 (40.9%) patients to have been identified with a molecular diagnosis. @*Conclusion@#This study showed a 40.9% diagnostic yield for WES test for a heterogeneous patient cohort with suspected rare genetic diseases. WES could be the feasible genetic test modality to overcome the diversity and complexity of rare disease diagnostics.

Co-occurrence of both maternally inherited neurofibromatosis type 1 and Lesch-Nyhan disease in a child with severe neurodevelopmental impairment

Lesch-Nyhan disease (LND) is a rare X-linked recessive inherited purine metabolic disorder that accompanies neurodevelopmental problems. Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant inherited genetic disorder characterized by tumors in various systems. Some children with NF1 also accompanies neurodevelopmental problems.Here, we describe a 5-year-old boy with a maternally inherited pathogenic variant in NF-1 and hypoxanthine-guanine phosphoribosyltransferase (HPRT ). He was referred for severe neurodevelopmental impairment and hyperuricemia. His mother was diagnosed with NF1 and the patient was also suspected of having NF1 because of cafe au lait macules. He had dystonia, rigidity, cognitive deficit, and speech/language impairment. Serum and urine uric acid concentrations were elevated. He had more severe neurodevelopmental delay than patients with only NF1, so his clinical symptoms could not be fully understood by the disease alone. To find the cause of his neurologic symptoms and hyperuricemia, the patient and his mother underwent a whole-exome sequencing test. As a result, the pathogenic variant c.151C>T (p.Arg51Ter) in HPRT1 was identified as hemizygote in the patient and heterozygote in his mother. The pathogenic variant c.7682C>G (p.Ser2561Ter) in NF-1 was identified as heterozygotes in both of them. Although the clinical symptoms of both diseases were overlapping and complicated, genetic testing was helpful for accurate diagnosis and treatment. Therefore, we suggest to consider preemptive genetic evaluation if there are symptoms not sufficiently explained by known existing diseases. And it is considered valuable to review this rare case to understand the clinical course and possible synergic effects of these diseases.

Two Korean siblings with autosomal recessive spinocerebellar ataxia 20 caused by homozygous variants in SNX14

Autosomal recessive spinocerebellar ataxia 20 (SCAR20; OMIM #616354) is a recently described disorder that is characterized by ataxia, intellectual disability, cerebellar atrophy, macrocephaly, coarse face, and absent speech. It is caused by lossof-function mutations in SNX14. To date, all cases with homozygous pathogenic variants have been identified in consanguineous families. This report describes the first Korean cases of SCAR20 family caused by homozygous variants in SNX14. Two siblings were referred to our clinic because of severe global developmental delay. They presented similar facial features, including a high forehead, long philtrum, thick lips, telecanthus, depressed nasal bridge, and broad base of the nose. Because the older sibling was unable to walk and newly developed ataxia, repeated brain magnetic resonance imaging (MRI) was performed at the age of 4 years, revealing progressive cerebellar atrophy compared with MRI performed at the age of 2 years.The younger sibling’s MRI revealed a normal cerebellum at the age of 2 years. Whole-exome sequencing was performed, and homozygous variants, such as c.2746-2A>G, were identified in SNX14 from the older sibling. Sanger sequencing confirmed homozygous SNX14 variants in the two siblings as well as a heterozygous variant in both parents. This report extends our knowledge of the phenotypic and mutational spectrum of SCAR20. We also highlight the importance of deep phenotyping for the diagnosis of SCAR20 in individuals with developmental delay, ataxia, cerebellar atrophy, and distinct facial features.

Postoperative Clinical Outcomes of Colonic Stent Placement as Bridge-to-surgery vs. Emergency Surgery in Left-sided Malignant Colonic Obstruction / 대한소화기암학회지

Background/Aims@#Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction. However, since its benefits are uncertain, we aimed to establish whether it has better clinical outcomes. @*Methods@#The patients with acute malignant left-sided colon obstruction enrolled from January 2009 to December 2018 in National Health Insurance Service Ilsan Hospital. The patients were enrolled to undergo colonic stenting as a bridge to elective surgery or emergency surgery. The following oncological outcomes were assessed: incidence of complete remission, disease progression, local recurrence, and systemic recurrence. @*Results@#Out of 40 patients, 33 received self-expanding metallic stent (SEMS) as a bridge-tosurgery, and 7 underwent emergency surgery. More stoma was made in case of emergency surgery with statistical significance (p < 0.001). There were no significant differences in complete remission rate in curable left-sided malignant colonic obstruction between SEMS as a bridgeto-surgery and emergency surgery. Complete remission was achieved for 3 patients (42.9%) in the non-stent group and 27 patients (81.8%) in the stent group. There was no statistically significant difference in oncologic outcomes between the two groups (p = 0.069). According to multi-variate analysis, advanced TNM stage, Adjuvant chemotherapy, and SEMS bridge-tosurgery were significantly associated with disease-free survival. Disease-free survival rate differed significantly between the two groups (p = 0.024). @*Conclusions@#SEMS as a bridge-to-surgery might be an effective strategy and reduce stoma formation in acute malignant left-sided colon obstruction.

Morning Glory Syndrome associated with Autosomal Dominant Alport Syndrome with a Heterozygous COL4A4 Mutation

Morning glory syndrome (MGS) is a rare congenital optic disc anomaly with a characteristic fundal finding with severe visual impairment. It may occur in association with various systemic manifestations, even though most of the reported cases were isolated. A 6-year-old male visited the nephrology clinic with a history of microscopic hematuria and at the age of 12 years, he was diagnosed thin glomerular basement membrane nephropathy by kidney biopsy. After the following years, the patient had progressive deterioration of visual acuity, and diagnosed as MGS. Whole Exome Sequencing of this patient and his mother revealed heterozygous COL4A4 mutations [c.81_86del (p.Ile29_Leu30del)]. It is more reasonable to consider MGS seen in this patient as a coincidental finding of autosomal dominant Alport syndrome. To our knowledge, this case represents the first case report of autosomal dominant Alport syndrome associated with MGS.

Empty Sella Syndrome Associated with Growth Hormone Deficiency:the First Case Report of WeissKruszka 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.

Empty Sella Syndrome Associated with Growth Hormone Deficiency:the First Case Report of WeissKruszka 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.

Risk for metabolic syndrome in the population with visceral fat area measured by bioelectrical impedance analysis

Background/Aims@#To investigate whether visceral fat area (VFA) measured by bioelectric impedance analysis (BIA) was associated with metabolic syndrome in subjects with and without obesity. @*Methods@#A total 23,202 participants who underwent medical check-ups were assessed. Participants were stratified by body mass index (BMI) and VFA. We evaluated six different groups for metabolic syndrome: Group 1 (normal weight and low VFA), Group 2 (normal weight and high VFA), Group 3 (overweight and low VFA), Group 4 (overweight and high VFA), Group 5 (obesity and low VFA), and Group 6 (obesity and high VFA). @*Results@#Metabolic syndrome traits and metabolic syndrome were significantly more prevalent in the high-VFA (≥ 100 cm2 ) subgroup in each BMI group. Adjusted logistic regression analyses revealed that the odds ratio for metabolic syndrome compared with Group 1 was the highest in Group 6 (24.53; 95% confidence interval [CI], 21.77 to 27.64). Notably, the odds ratio of Group 2 was higher than that of Group 3 (2.92; 95% CI, 2.30 to 3.69 vs. 2.57; 95% CI, 2.23 to 2.97). @*Conclusions@#Our study demonstrates that the combination of BMI assessment and VFA determination by BIA may be a useful method for predicting the risk of metabolic syndrome. The VFA by BIA may be a useful target for interventions to improve metabolic syndrome.

Hypotonia, Ataxia, and Delayed Development Syndrome caused by the EBF3 mutation in a Korean boy with muscle hypotonia

Hypotonia, Ataxia, and Delayed Development Syndrome (HADDS) is an autosomal-dominant, extremely rare neurodevelopmental disorder caused by the heterozygous EBF3 gene mutation. EBF3 is located on chromosome 10q26.3 and acts as a transcription factor that regulates neurogenesis and differentiation. This syndrome is characterized by dysmorphism, cerebellar hypoplasia, urogenital anomaly, hypotonia, ataxia, intellectual deficit, and speech delay. The current report describes a 3-year-old Korean male carrying a de novo EBF3 mutation, c.589A>G (p.Asn197Asp), which was identified by whole exome sequencing. He manifested facial dysmorphism, hypotonia, strabismus, vermis hypoplasia, and urogenital anomalies, including vesicoureteral reflux, cryptorchidism, and areflexic bladder. This is the first report of a case of HADDS cause by an EBF3 mutation in the Korean population.

An A627V-activating mutation in the thyroid-stimulating hormone receptor gene in familial nonautoimmune hyperthyroidism

Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves’ disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.

Hypotonia, Ataxia, and Delayed Development Syndrome caused by the EBF3 mutation in a Korean boy with muscle hypotonia

Hypotonia, Ataxia, and Delayed Development Syndrome (HADDS) is an autosomal-dominant, extremely rare neurodevelopmental disorder caused by the heterozygous EBF3 gene mutation. EBF3 is located on chromosome 10q26.3 and acts as a transcription factor that regulates neurogenesis and differentiation. This syndrome is characterized by dysmorphism, cerebellar hypoplasia, urogenital anomaly, hypotonia, ataxia, intellectual deficit, and speech delay. The current report describes a 3-year-old Korean male carrying a de novo EBF3 mutation, c.589A>G (p.Asn197Asp), which was identified by whole exome sequencing. He manifested facial dysmorphism, hypotonia, strabismus, vermis hypoplasia, and urogenital anomalies, including vesicoureteral reflux, cryptorchidism, and areflexic bladder. This is the first report of a case of HADDS cause by an EBF3 mutation in the Korean population.

An A627V-activating mutation in the thyroid-stimulating hormone receptor gene in familial nonautoimmune hyperthyroidism

Nonautoimmune hyperthyroidism is a very rare cause of congenital hyperthyroidism that is usually caused by an activating mutation in the thyroid-stimulating hormone receptor (TSHR) gene. In this report, we describe a case of nonautoimmune hyperthyroidism in a patient with TSHR mutation. Our patient was the younger of a set of twins born at 36 weeks and 6 days of gestation. The patient was noted to be more irritable than the older twin at 80 days of age, and the mother was taking methimazole for Graves’ disease that had been diagnosed 12 years prior. Therefore, a thyroid function test was conducted for the patient. The results revealed subclinical hyperthyroidism, and tests of antithyroglobulin antibody, antithyroid peroxidase antibody, and anti-thyroid-stimulating hormone (TSH) receptor antibody were all negative. During follow-up, at around 4 months of age, free T4 increased to 2.89 ng/dL, and TSH was still low at 0.01 μIU/mL; therefore, 3 mg/day of methimazole was initiated. Whole-exome sequencing showed a heterozygous variant of c.1800C>T (p.Ala627Val) in the TSHR gene. Testing in the family confirmed an identical variant in the patient's mother, leading to diagnosis of familial nonautoimmune hyperthyroidism inherited in an autosomal dominant pattern. This is the second report of A627V confirmed as a germline variant.

Epidemiology of urticaria including physical urticaria and angioedema in Korea

BACKGROUND/AIMS@#Despite the high burden and frequency of urticaria, its epidemiology is not well known. We investigated the epidemiology of various type of urticaria in Korea and changes in its annual prevalence over 5 years.@*METHODS@#We used data from the 2010 to 2014 Health Insurance Review and Assessment database, which covers the claims of 97.0% of the South Korean population. Patients aged > 10 years old were included in this study. The presence of urticaria was identified on physician-certified diagnoses using the International Classification of Diseases 10th Revision (ICD-10) codes that include various type of urticaria (L500–L509) and angioedema (T783). Epidemiology of all type of urticaria, physical urticaria and angioedema were investigated.@*RESULTS@#The prevalence of all-type urticaria over the 5 years was 4.5% with a peak in individuals, especially females, aged 30 to 59 years. The age-specific prevalence of all-type urticaria increased with age from the 10- to 19-year age group to the 70- to 79-year age group. The prevalence of dermographism, cholinergic urticaria, and angioedema were 0.12%, 0.025%, and 0.027%, respectively. Cholinergic urticaria was most prevalent in those aged 10 to 29 years with male predominance. The annual prevalence of all-type urticaria, dermographism, and angioedema increased over the 5 years.@*CONCLUSIONS@#The prevalence of urticaria has increased annually in Korea. Cholinergic urticaria showed unique distribution in its age and gender, and angioedema showed remarkable increases in annual prevalence, although the prevalence estimation is still exploratory and diagnosis of urticaria based on ICD-10 codes need to be validated.

An ANKRD11 exonic deletion accompanied by a congenital megacolon in an infant with KBG syndrome

KBG syndrome is an autosomal dominant syndrome presenting with macrodontia, distinctive facial features, skeletal anomalies, and neurological problems caused by mutations in the ankyrin repeat domain 11 (ANKRD11) gene. The diagnosis of KBG is difficult in very young infants as the characteristic macrodontia and typical facial features are not obvious. The youngest patient diagnosed to date was almost one year of age. We here describe a 2-month-old Korean boy with distinctive craniofacial features but without any evidence of macrodontia due to his very early age. He also had a congenital megacolon without ganglion cells in the rectum. A de novo deletion of exons 5–9 of the ANKRD11 gene was identified in this patient by exome sequencing and real-time genomic polymerase chain reaction. As ANKRD11 is involved in the development of myenteric plexus, a bowel movement disorder including a congenital megacolon is not surprising in a patient with KBG syndrome and has possibly been overlooked in past cases.

Ehlers-Danlos syndrome VIII with novel C1R variant accompanying white matter changes

Ehlers-Danlos syndrome (EDS) VIII is an autosomal dominant inherited connective tissue disorder characterized by intractable periodontal inflammation, absence of gingiva, pretibial plaques, skin hyperextensibility, joint hypermobility, and tissue fragility with onset in the childhood or adolescence. In a recent report, heterozygous variants of the C1R or C1S related to the classical complement pathway were identified in families with history of EDS VIII. The current report describes a Korean 34-year-old female carrying a novel missense variant of C1R c.925T>G (p.Cys309Gly) and exhibiting early severe periodontitis, skin fragility, and joint hypermobility. The patient also had frontal, parietal, and temporal white matter brain lesions without definite vascular abnormalities on brain magnetic resonance imaging, which have not been surveyed meticulously in EDS VIII. Considering the genetic alteration of classic complement pathways in this condition, it is necessary to carefully observe multisystemic inflammation processes such as changes in brain white matter.

Continuous Infusion versus Intermittent Dosing with Pantoprazole for Gastric Endoscopic Submucosal Dissection

BACKGROUND/AIMS: Proton pump inhibitors are widely used to prevent gastric endoscopic submucosal dissection (ESD)-related bleeding, but no standard administration regimens have been established. We aimed to prospectively compare the effects of continuous infusion and intermittent dosing with pantoprazole on preventing gastric ESD-related bleeding. Additionally, we analyzed the risk factors for bleeding. METHODS: From April 2012 to May 2013, patients with a gastric epithelial neoplasm scheduled for ESD in the Pusan National University Hospital were randomly assigned to one of two groups according to the pantoprazole administration regimen (continuous infusion or intermittent dosing). The primary outcomes measured were intra- and postprocedural bleeding events. RESULTS: The final analysis included 401 patients. The rate of significant intraprocedural bleeding was 25.4% in the C group and 24.0% in the I group, with no significant difference (p=0.419). In addition, there was no significant difference in the postprocedural bleeding rate between the C and I groups (11.7% vs 10.2%, p=0.374). Multivariate analysis showed that intraprocedural bleeding was associated with the proximal tumor location, the presence of fibrosis, and the size of the resected specimen, whereas postprocedural bleeding was associated with the size of the resected specimen and the procedure/coagulation time. CONCLUSIONS: Intermittent dosing with pantoprazole is sufficient and cost-effective for the prevention of gastric ESD-related bleeding. Operators should consider tumor characteristics when planning ESD to minimize the risk of intraprocedural bleeding, and patients with large iatrogenic ulcers should be carefully monitored for postprocedural bleeding.

Joint Attention Virtual Classroom: A Preliminary Study

OBJECTIVE: Previous studies have suggested that a virtual classroom is immersive and ecologically valid neuropsychological assessment, but those studies have limited components for social attentions. Therefore, the objective in the current study is the development of a joint attention virtual reality (JA-VR) classroom to incorporate social attentions between a participant and a virtual avatar teacher. METHODS: Fifty-eight participants were recruited for current study (25 for pilot and 33 for main studies; 32.8% female, n=19; age: M=24.5, SD=4.0). We suggested a JA-VR classroom, and compared it with previous methods including a VR classroom without JA components. We conducted attention experiments with AX-version of continuous performance tasks. RESULTS: Our results suggest that the new JA-VR classroom had convergent validity with previous methods, and that the JA-VR classroom promoted attentional processing among participants better than both old VR and non-VR measures. CONCLUSION: We add an important social attention concept to the virtual classroom, and believe that this work is an methodological foundation for the study of social attention in school life. We hope it ultimately help people with mental handicaps in social attention.

Growth hormone therapy in patients with Noonan syndrome

Noonan syndrome (NS) is an autosomal dominant disorder that involves multiple organ systems, with short stature as the most common presentation (>70%). Possible mechanisms of short stature in NS include growth hormone (GH) deficiency, neurosecretory dysfunction, and GH resistance. Accordingly, GH therapy has been carried out for NS patients over the last three decades, and multiple studies have reported acceleration of growth velocity (GV) and increase of height standard deviation score (SDS) in both prepubertal and pubertal NS patients upon GH therapy. One year of GH therapy resulted in almost doubling of GV compared with baseline; afterwards, the increase in GV gradually decreased in the following years, showing that the effect of GH therapy wanes over time. After four years of GH therapy, ~70% of NS patients reached normal height considering their age and sex. Early initiation, long duration of GH therapy, and higher height SDS at the onset of puberty were associated with improved final height, whereas gender, dosage of GH, and the clinical severity did not show significant association with final height. Studies have reported no significant adverse events of GH therapy regarding progression of hypertrophic cardiomyopathy, alteration of metabolism, and tumor development. Therefore, GH therapy is effective for improving height and GV of NS patients; nevertheless, concerns on possible malignancy remains, which necessitates continuous monitoring of NS patients receiving GH therapy.

Hepatopulmonary syndrome caused by hypothalamic obesity and nonalcoholic fatty liver disease after surgery for craniopharyngioma: a case report

Hypothalamic obesity is often complicated in patients with craniopharyngioma due to hypothalamic damage by the tumor itself, treatment modalities, and associated multiple pituitary hormone deficiency. Hypothalamic obesity causes secondary diseases such as nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM). We report a 19-year-old female who was diagnosed with craniopharyngioma, developed hypothalamic obesity after tumor resection, and progressed to hepatopulmonary syndrome. She manifested NAFLD 1 year after tumor resection. Two years later, the craniopharyngioma recurred, and she underwent a second resection. Three years after her second operation, she was diagnosed with type 2 DM, after which she did not visit the outpatient clinic for 2 years and then suddenly reappeared with a weight loss of 25.8 kg that had occurred over 21 months. One month later, she presented to the Emergency Department with dyspnea. Laboratory findings revealed liver dysfunction and hypoxia with increased alveolar artery oxygen gradient. Liver biopsy showed portal hypertension and micronodular cirrhosis. Echocardiography and a lung perfusion scan demonstrated a right to left shunt. She was finally diagnosed with hepatopulmonary syndrome and is currently awaiting a donor for liver transplantation. Patients surviving craniopharyngioma need to be followed up carefully to detect signs of hypothalamic obesity and monitored for the development of other comorbidities such as DM, NAFLD, and hepatopulmonary syndrome.