Genotypic and phenotypic features of 39 Chinese patients with glycogen storage diseases type I, VI, and IX.

Glycogen storage diseases (GSDs) are abnormally inherited glycogen metabolism mainly affecting the liver, muscles, and heart. Deficiency of proteins involved in glycogen metabolism caused by genetic mutations are responsible for different subtype of GSDs. However, there are still some challenges in diagnosing GSD. This study includes 39 suspected GSDs patients from unrelated families in China. Next-generation sequencing (NGS) was used to investigate the reason for their diseases at the genetic level. Finally, all 39 patients were diagnosed with GSDs, including 20 GSD-Ia, 4 GSD-VI, and 15 GSD IX (12 GSD-IXa patients and 3 GSD-IXb patients). Thirty-two mutations in G6PC1, PYGL, PHKA2, and PHKB genes were identified, with 14 of them being novel variants. The pathogenicity of novel variants was classified according to ACMG guildlines and predicted by in slico algorithms. Mutations p.L216L and p.R83H in G6PC1 gene may be the hot spot mutation in Chinese. Hearing impairment is a rare clinical feature of GSD Ia, which has also been observed in our cohort. The severity of GSD VI and IX was indicated by our patients. Close follow-up should be applied to GSD VI and IX patients. Our findings provided evidence for building the phenotype-genotype of GSDs and expanded the mutation spectrum of related genes.

Genetic analysis of PYGL gene variants for a child with Glycogen storage disease VI / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic basis of a patient with glycogen storage disease type VI (GSD-VI).@*METHODS@#Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples of the proband and his parents. Genetic variants were detected by using whole exome sequencing. Candidate variants were verified by Sanger sequencing followed by bioinformatics analysis.@*RESULTS@#The proband presented fasting hypoglycemia, hepatomegaly, growth retardation, transaminitis, metabolic acidosis and hyperlactatemia. Liver biopsy indicated GSD. Novel compound heterozygous PYGL gene variants (c.2089A>G/c.158_160delACT) were detected in the proband. Compound heterozygosity was confirmed by Sanger sequencing of the patient's genomic DNA. Provean and MutationTaster predicted the two variants as deleterious and the variant sites are highly conserved.@*CONCLUSION@#The compound heterozygous variants (c.2089A>G/c.158_160delACT) of PYGL gene probably underlay the GSD in the patient. The two novel variants have expanded the spectrum of PYGL gene variants and provided the basis for genetic counseling of the family.

A Case of Paradoxical Flare of Pustular Psoriasis after Ustekinumab Therapy / 대한피부과학회지

Biologics are the most advanced treatment for psoriasis. Ustekinumab, one of the biologics for psoriasis, is a human monoclonal antibody that binds to the p40 subunit of interleukin-12 and interleukin-23. A 41-year-old woman with a 17-year history of plaque psoriasis and psoriatic arthritis presented with worsening lesions. The patient had previously been treated with a number of topical and systemic medications and narrow band ultraviolet B. However, none of the treatments consistently controlled her disease. Thus, treatment with ustekinumab 45 mg via subcutaneous injection was initiated. Approximately 7 days after the first treatment, she experienced a flare with generalized pustules in her whole body. The condition was controlled with systemic steroid treatment. The patient was subsequently treated with adalimumab, and improvement in her plaque and pustular lesions was noted. Herein, we report a case of psoriasis that flared up after ustekinumab therapy, which was accompanied by a morphological change from plaque to pustular lesions.

A Case of Catatonia Later Diagnosed with NMDA Receptor Encephalitis / 대한정신분열병학회지

We report a case of a young female patient with catatonic features who later turned out to be suffering from an anti-NMDA (N-methyl-D-aspartate)-receptor-antibody encephalitis. A previously healthy 21-year-old woman was admitted to psychiatric inpatient care presenting with acute psychotic behavior with catatonic features. Laboratory tests of serum and CSF (Cerebrospinal fluid), EEG (Electroencephalogram), brain MRI (Magnetic Resonance Imaging) were unremarkable except vague slow wave on EEG. However, subtle cognitive impairment at the bedside examination suggested further imaging studies to rule out possible organic etiology like autoimmune encephalitis. Brain PET (Positron Emission Tomography) and SPECT (Single Photon Emission Computed Tomography) suggested probable inflammation in the brain. In case of autoimmune encephalitis, given the severity of symptoms and worsening course, steroid pulse therapy was initiated promptly even though the diagnosis was not confirmed but presumed at that time. She recovered completely with steroid therapy. Later her disease turned out to be anti-NMDA-receptor-antibody encephalitis by the antibody test which was not available at the time of admission. Psychiatrists need to be aware of autoimmune encephalitis like anti-NMDA-receptor-antibody encephalitis in the differential diagnosis of acute psychosis with catatonic features. Subtle cognitive impairment which tends to be overlooked due to catatonic features might be a clue to suspect the organic etiology.

Dermatomyositis: A Rare Extra-intestinal Manifestation of Ulcerative Colitis

Inflammatory myositis as an extra-intestinal manifestation of inflammatory bowel disease (IBD) is rare. Coexistence of immuno-mediated diseases in patients with IBD and myositis suggests a common etiopathogenic mechanism underlying these conditions. The current report refers to a rare case of a 45-year-old Korean female with ulcerative colitis (UC) who developed dermatomyositis. She presented with skin rash and proximal muscle weakness, and her disease activity of UC was in remission state. Electromyography, magnetic resonance imaging, and deltoid muscle biopsy were performed. She was diagnosed with dermatomyositis associated with UC and treatment with glucocorticoids and azathioprine resulted in improvement in muscle power and skin rash. Clinicians should be aware of this unusual extra-intestinal manifestation.

Relapsed Wilms' tumor with multiple brain metastasis / 소아과

Wilms' tumor is the most common malignant renal tumor in childhood. The brain metastasis of a Wilms' tumor with anaplastic histopathology is rare. We present the case of an 8-year-old girl with Wilms' tumor, who presented with multiple brain metastases 5 years after her primary diagnosis. The brain masses were diagnosed after a generalized tonic-clonic seizure attack. The big solid mass in the cerebellum was resected, and whole-brain radiotherapy was performed, after which, she succumbed to her disease. In the case of clinical suspicion, cranial surveillance should be included in the routine clinical work-up for Wilms' tumor. Combined aggressive therapy (surgery+radiotherapy+chemotherapy) should be applied whenever possible, for both better survival and palliative aspects.

Uterine Cervix Metastasis in Lung Adenocarcinoma with Anaplastic Lymphoma Kinase Rearrangement

The importance of anaplastic lymphoma kinase (ALK) as an oncogene in non-small cell lung cancer (NSCLC) has emerged as a major concern due to a dramatic clinical effect of targeted therapy. As compared with the research for targeted therapy, the study about clinicopathological characteristics for ALK positive NSCLC hasn't been worked enough. Here, we describe a 35-year-old woman diagnosed with stage IVb NSCLC with ALK rearrangement. During evaluating her disease, a metastatic lesion to uterine cervix was found. Although lung cancer metastasis to female genital tract is rare, we also present case series that show a metastasis to the female genital tract in NSCLC with ALK rearrangement. These case series could suggest that ALK positive NSCLC has distinct metastatic pattern.

Refractory Graves' Disease Successfully Cured by Adjunctive Cholestyramine and Subsequent Total Thyroidectomy

The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with thionamides or inorganic iodine. But several cases of refractory Graves' disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves' disease who complained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves' disease. One kind of thionamides and beta-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including beta-blockers, inorganic iodine, and two thionamides. She experienced hepatotoxicity from the thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunctive agent for preoperative preparation in patients with severe hyperthyroid Graves's disease that is resistant to conventional therapies.

Adult-Onset Still's Disease with Thrombotic Thrombocytopenic Purpura / 대한내과학회지

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that affects multiple organs and is fatal in some cases. Thrombotic thrombocytopenic purpura (TTP), another rare disease, is characterized by multiple organ failure and microangiopathic hemolytic anemia. TTP is an extremely rare complication of AOSD. We report a 59-year-old woman who presented with TTP that manifested after she was diagnosed with AOSD. Initially, her clinical manifestations improved with glucocorticoid therapy. However, her disease worsened and was accompanied by acute kidney injury, thrombocytopenia, hemolytic anemia, petechiae, and impaired consciousness. These clinical findings led to a diagnosis of TTP. This is the first report of AOSD complicated by TTP in Korea. Awareness of the possible development of TTP as a complication of AOSD is important for early diagnosis and treatment.

A Case of Cytomegalovirus-associated Giant Gastric Ulcer in a Patient Who Healed by Discontinuing Immunosuppressive Therapy

Cytomegalovirus (CMV) is not a rare infection and is frequently observed in immuoncompromised patients. CMV infection is usually asymptomatic in immunocompetent patients however it can be a major cause of morbidity and mortality in immunocompromised patients. The diagnosis of CMV gastric ulcer is not easy because of the absence of characteristic endoscopic features and the difficulty in the identification of infection by routine histologic examinations. We experienced a case of CMV-associated giant gastric ulcer in a patient receiving immunosuppressive therapy. She was a 45-year-old woman with dermatomyositis and had received steroid therapy to control her disease. Epigastric pain developed during therapy and upper endoscopy revealed a gastric ulcer. Despite proton pump inhibitor therapy, her epigastric pain aggravated and follow-up endoscopy revealed a huge gastric ulcer approximately 10 cm in diameter. Histologic findings showed intracellular inclusion bodies after immunostaining which confirmed CMV-associated gastric ulcer. Steroid therapy was discontinued and she received proton pump inhibitors without antiviral agents. Her symptoms improved and follow-up endoscopy revealed successful healing of the CMV-associated gastric ulcer. If an unusual gastric ulcer develops in the immunocompromised patients, CMV gastric ulcer should be suspected and examination for inclusion bodies using CMV immunostaining should be considered.

Adenoid Cystic Carcinoma of the Breast: A Case Series of Six Patients and Literature Review / Journal of the Korean Cancer Association, 대한암학회지

Adenoid cystic carcinoma (ACC) of the breast is a very rare and indolent tumor with a favorable prognosis, despite its triple-negative status. Due to its rarity, there has been no consensus regarding treatments, and treatment guidelines have not been established. Here, we report on six patients with ACC of the breast. All of the patients initially presented with localized disease and no axillary lymph node metastases. Although some of our patients developed local recurrence or distant metastases, all patients had a favorable clinical course, and to date, none of the patients has died from complications of her disease. Here, we described the clinicopathologic features of ACC of the breast and review the current literature.

Adenoid Cystic Carcinoma of the Breast: A Case Series of Six Patients and Literature Review / Journal of the Korean Cancer Association, 대한암학회지

Adenoid cystic carcinoma (ACC) of the breast is a very rare and indolent tumor with a favorable prognosis, despite its triple-negative status. Due to its rarity, there has been no consensus regarding treatments, and treatment guidelines have not been established. Here, we report on six patients with ACC of the breast. All of the patients initially presented with localized disease and no axillary lymph node metastases. Although some of our patients developed local recurrence or distant metastases, all patients had a favorable clinical course, and to date, none of the patients has died from complications of her disease. Here, we described the clinicopathologic features of ACC of the breast and review the current literature.

Successful Treatment of Primary Biliary Cirrhosis with Adalimumab in a Patient with Overlap Syndrome

Primary biliary cirrhosis (PBC) is occasionally developed in patients with rheumatic diseases, such as systemic sclerosis or Sjogren's syndrome. However, there are a few reports of overlap syndrome with PBC. The authors report a case of a 36 year-old female with PBC and overlap syndrome. Systemic sclerosis was diagnosed in 2007, and rheumatoid arthritis in 2010. Adalimumab stopped because of her pregnancy plan in January 2012. One month after delivery, she felt increased hand joint pain and fatigue. Laboratory findings were as follows: elevated AST, ALT, ALP, r-GTP and positive anti-mitochondrial antibody. Histology of a liver biopsy revealed moderate porto-periportal and mild lobular inflammation with bile duct inflammation, which was consistent with PBC. She was treated with prednisolone and UDCA (urosodeoxycholic acid), but her disease was not controlled. From May 2013, she has been treated with adalimumab. Her arthritis was improved and liver function test normalized up until now.

A Case of Skin Sclerosis Associated with Docetaxel Chemotherapy for Non-Small Cell Lung Cancer

A 64-year-old woman was diagnosed with non-small cell lung cancer. Her disease was stage 4 (T2N2M1) with squamous cell carcinoma. She had been treated with docetaxel and carboplatin. After a completion of 11 cycle of chemotherapy, edema appeared on both feet and had spread rapidly up to the pretibial area without response to diuretics. Sclerotic changes and pigmentation followed but both knees and other parts of the body were spared. There was no evidence of vascular occlusions. On serologic tests, antinuclear, anti-centromere, and anti-topoisomerase I antibodies were all negative. A skin biopsy revealed diffuse infiltration of lymphocytes and discretely thickened collagen bundles in the superficial dermis. After discontinuing docetaxel chemotherapy, she was treated with prednisolone and D-penicillamine and sclerotic changes on the lower legs were improved.

A Case of Hypersensitivity Pneumonitis with Giant Cells in a Female Dental Technician

OBJECTIVES: Dental technicians are exposed to methyl methacrylate(MMA) and hard metal dusts while working, and several cases of hypersensitivity pneumonitis caused by the exposure have been reported. The authors experienced a case of hypersensitivity pneumonitis in a female dental technician who had 10 years' work experience and report the case with clinical evidence. METHOD: The patient's work, personal, social, and past and present medical histories were investigated based on patient questioning and medical records. Furthermore, the workplace conditions and tools and materials the patient worked with were also evaluated. Next, the pathophysiology and risk factors of pneumonitis were studied, and studies on the relationship between hypersensitivity pneumonitis and a dental technician's exposure to dust were reviewed. Any changes in the clinical course of her disease were noted for evaluation of the work-relatedness of the disease. RESULTS: The patient complained of cough and sputum for 1 year. In addition, while walking up the stairs, the patient was not able to ascend without resting due to dyspnea. She visited our emergency department due to epistaxis, and secondary hypertension was incidentally suspected. Laboratory tests including serologic, electrolyte, and endocrinologic tests and a simple chest radiograph showed no specific findings, but chest computed tomography revealed a centrilobular ground-glass pattern in both lung fields. A transbronchial biopsy was performed, and bronchoalveolar washing fluid was obtained. Among the findings of the laboratory tests, microcalcification, noncaseating granuloma containing foreign body-type giant cells, and metal particles within macrophages were identified histologically. Based on these results, hypersensitivity pneumonitis was diagnosed. The patient stopped working due to admission, and she completely quit her job within 2 months of restarting work due to reappearance of the symptoms. CONCLUSION: In this study, the patient did not have typical radiologic findings, but pathological evaluation of the lung biopsy from the bronchoscope led to the suspicion of pneumonitis. Under the microscope, the sample contained fibrotic changes in the lung, multinucleated giant cells, and particles in macrophages and was diagnosed as dental technician pneumoconiosis by the pathology. Working as a dental technician had directly exposed her to light metal dust and MMA, and her clinical symptoms and radiologic findings subsided after withdrawal from exposure to the workplace. These outcomes led to the diagnosis of hypersensitity pneumonitis due to MMA exposure and strong work-relatedness.

A Case of Kienbock's Disease from Repetitive Contact Stress / 대한산업의학회지

OBJECTIVES: Kienbock's disease, which is characterized by osteonecrosis of the lunate bone, causes progressive chronic pain and dysfunction of the hand and wrist. Even though occurrence of the disease was reported approximately 100 years ago and it is suspected to be work-related to some degree, the etiology has not been clearly discribed and the disease has rarely been considered as an occupation-related disease. As such, we submit this case as the first report of Kienbock's disease in Korea, with clinical findings, x-ray, MRI (magnetic resonance imaging) and strain index results along with a literature review. METHODS: The patient was carefully interviewed and her medical records were properly reviewed by the authors with her consent. The authors also visited her factory work site to inspect and videotape the working environment and to conduct an ergonomic evaluation with a strain index. RESULTS: Excessively repeated contact stress was found to be concentrated on her right hand and the environment was discovered to be hazardous from an ergonomic standpoint. The literature review revealed that heavy loads on the hand might be related to the cause or deterioration associated with Kienbock's disease. ; therefore, it is very likely that her disease is related to her work. CONCLUSIONS: There is much evidence to suggest that heavy workloads involving hand and wrist intensive tasks may cause and worsen Kienbock's disease. However, to date epidemiologic studies clarifying the etiology of the disease have not been sufficiently reported. Therefore, further research focusing on the etiology and prevention of the disease are required. In addition, practical guidelines for hand and wrist intensive tasks are needed to prevent disease development and worsening.

A Case of Desmoplastic Small Round Cell Tumor Diagnosed in a Young Female Patient / Journal of the Korean Cancer Association, 대한암학회지

Desmoplastic small round cell tumor is a very rare malignancy. We report the case of a 26-year-old woman who suffered from dyspepsia and abdominal pain for 2 months. We performed an endoscopic biopsy of the duodenal mass and diagnosed her disease as desmoplastic small round cell tumor using immunohistochemical staining, fluorescence in situ hybridization, and reverse transcriptase polymerase chain reaction. Because the mass invaded the pancreas and superior mesenteric vein as well as duodenum and the disease was disseminated to liver and peritoneum, she received palliative chemotherapy using vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. The maximal response to chemotherapy was stable disease. The patient expired 9 months after diagnosis.

A Case of Ileal Mucormycosis in a Patient with Gastrointestinal Behcet's Disease

Zygomycosis (mucormycosis) is a rare fungal infectious disease, usually found in association with an immunocompromised state. Gastrointestinal mucormycosis is extremely rare and fatal, thus it is important to detect and manage this disease at an early stage in an effort to improve survival. To date, no cases of mucormycosis superimposed on gastrointestinal Behcet's disease have been reported. Herein we report a case in which gastrointestinal mucormycosis occurred in a 17-year-old-female with Behcet's disease. The patient recovered from her disease after undergoing an ileocecectomy.

A case of well-differentiated squamous cell carcinoma of the duodenum / 대한내과학회지

Squamous cell carcinoma of the duodenum is an extremely rare neoplasm worldwide. A 44-year-old female patient was admitted to our institution for abdominal pain, and she was diagnosed with primary squamous cell carcinoma of the duodenum. The duodenal cancer was inoperable due to vascular invasion and regional lymph node metastasis. The patient was treated with palliative chemotherapy, but her disease progressed, and she was eventually referred to a local hospital for supportive care. The prognosis of squamous cell carcinoma of the duodenum is poor compared with that of usual duodenal adenocarcinoma. We report the details of this case of squamous cell carcinoma of the duodenum along with a review of the literature.