Intractable & Rare Diseases Research Vol. 6(2017) No. 2

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with a prognosis that can be worse than that of many cancers. Recent studies have improved our understanding of IPF and new treatment options have become available. However, most studies are conducted predominantly in Western countries while few are conducted in East Asian countries. The distribution, effectiveness of treatment, and prognosis for IPF differ among Westerners and East Asians, but whether the heterogeneity of IPF in East Asians is the result of ethnic differences and geographic variability is unclear. This study highlights the current prevalence of IPF and its characteristics in the East Asian population and it provides valuable information to understand the current clinical status of patients with IPF in light of recent advances in its diagnosis and treatment.

Aortic intramural hemorrhage (IMH) is one of the disease processes that comprise the spectrum of acute aortic syndrome (AAS) with clinical manifestations and a mortality rate similar to those of classic aortic dissection (AD). However, IMH should be considered as a distinct disease entity rather than a precursor to classic dissection because of differences in their pathology, etiology, natural history, and imaging findings. Multidetector computed tomography (CT) is recommended as the first-line diagnostic imaging modality for IMH, but transesophageal echocardiography (TEE) and magnetic resonance imaging (MRI) are also helpful. There is still debate over the appropriate treatment of IMH. Medical treatment of type B IMH appears effective and safe, while surgical treatment is recommended for type A IMH. Thoracic endovascular aortic repair (TEVAR) is a promising treatment for selected patients, and more clinical evidence needs to be assembled.

Cardiomyopathy associated with dystrophinopathies [Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XL-dCM) and cardiomyopathy of Duchenne/Becker (DMD/BMD) carriers] is an increasing recognized manifestation of these neuromuscular disorders and notably contributes to their morbidity and mortality. Dystrophinopathic cardiomyopathy (DCM) is the result of the dystrophin protein deficiency at the myocardium level, parallel to the deficiency occurring at the skeletal muscle level. It begins as a "presymptomatic" stage in the first decade of life and evolves in a stepwise manner toward pictures of overt cardiomyopathy (hypertrophic stage, arrhythmogenic stage and dilated cardiomyopathy). The final stage caused by the extensive loss of cardiomyocytes results in an irreversible cardiac failure, characterized by frequent episodes of acute congestive heart failure (CHF), despite a correct pharmacological treatment. The picture of a severe dilated cardiomyopathy with intractable heart failure is typical of BMD, XL-dCM and cardiomyopathy of DMD/BMD carriers, while it is less frequently observed in patients with DMD. Heart transplantation (HT) is the only curative therapy for patients with dystrophinopathic end-stage heart failure who remain symptomatic despite an optimal medical therapy. However, no definitive figures exist in literature concerning the number of patients with DCM transplanted, and their outcome. This overview is to summarize the clinical outcomes so far published on the topic, to report the personal series of dystrophinopathic patients receiving heart transplantation and finally to provide evidence that heart transplantation is a safe and effective treatment for selected patients with end-stage DCM.

Hepatolithiasis is highly prevalent in Asia but rare in Western countries. However, the incidence of hepatolithiasis may be increasing in Western countries due to the increased rate of immigration from areas where hepatolithiasis is prevalent. There are many non-surgical treatments for hepatolithiasis, but surgical management remains the best curative treatment for some cases of hepatolithiasis. Surgical treatments can remove biliary stones and relieve stricture of the bile ducts. This review describes the indications for and the outcomes of surgical treatment of hepatolithiasis, including liver resection and liver transplantation.

Pediatric ulcerative colitis (UC) sometimes progresses to an intractable condition for medical therapy. The surgical management of UC is challenging because of difficult procedures and frequent infectious complications. The aim of this study was to survey surgical procedures and infectious complications in pediatric patients with UC in Japan and to assess the relationship between preoperatively administered immunosuppressive drugs and postoperative surgical site infection (SSI). A survey of pediatric patients treated from 2000 to 2012 was sent to 683 facilities nationwide. Secondary questionnaires were sent to physicians who followed up patients with UC who had undergone surgery with the aim of assessing the relationships between postoperative SSI and selected preoperative patient characteristics, disease severity, medications, and operative procedures. Data for 136 patients (77 boys and 59 girls) were assessed. Median age at surgery was 14.1 years (range: 2.4-18.9 years). Surgery was performed in one stage in 35 cases, two stages in 57 cases, and three stages in 44 cases. SSI occurred in 36/136 patients (26%). According to multiple logistic regression analysis, there were statistically significant associations between SSI and staged surgery (three/one, OR: 6.7, 95% CI: 2.1-25.5, p = 0.0007; three/two, OR: 3.4, 95% CI: 1.4-8.6, p = 0.0069) and female sex (OR: 2.3, 95% CI: 1.0-5.4, p = 0.0434). Preoperative medications and incidence of SSI were not significantly associated. Preoperative immunosuppressive medication does not affect the incidence of SSI. Three-stage surgery and female sex are independent predictors of development of postoperative SSIs in pediatric patients with UC.

Dent disease is an X-linked recessive proximal tubular disorder that affects mostly male patients in childhood or early adult life, caused by mutations in CLCN5 (Dent disease 1) or OCRL (Dent disease 2) genes, respectively. It presents mainly with hypercalciuria, low- molecular-weight proteinuria, nephrocalcinosis and progressive renal failure. We report here the same CLCN5 mutation but different phenotypes in two Chinese brothers, and speculate on the possible reasons for the variability of the genotype-phenotype correlations.

Mucopolysaccharidosis IV A, better known as Morquio-A syndrome, is a rare condition with severe skeletal and multiorgan involvement. Sometimes is not easy to differentiate from other skeletal dysplasias. Prior to definitive diagnosis, patients have been delayed or misdiagnosis due to lack of knowledge of local physicians about this disease. The aim of this study is to compare the age of onset of clinical manifestations, age of diagnosis, as seen by the parent or primary caregiver and compare this age with other population reports worldwide. Self-administered questionnaires were conducted to the primary caregiver of confirmed patients, collecting information about the onset of symptoms, age, previous diagnoses and biological variables (age, gender, sex). Data from 50 patients, 23 men and 27 women was obtained. Mean age at definitive diagnosis was 5.6 years, age at onset of signs or symptoms was 4.14 years starting with pigeon chest deformity, valgus knees at 4.5 years, stiff hands and increasing mobility of wrists to the 5.8 years, followed by limitation to lift shoulders to 7.1 years. In 78% of patients the diagnosis was by a geneticist. First and subsequent observed clinical changes were orthopedic, starting as early as 4.4 years as noted by parents. Rise of suspicious may delay 16 months' average to definitive diagnosis based on other multi-systemic findings. The most frequent specialist aid in diagnosis is a clinical geneticist followed by orthopedic surgeon. The diagnosis of Morquio-A disease in Mexico is as early as reports from other centers.

We present a middle aged pregnant woman who developed signs and symptoms of acute liver failure and was found to have herpes simplex virus hepatitis. Patient had an emergent delivery and was started on antiviral therapy, but unfortunately due to the severity of her liver failure, she passed away. The importance of reporting this case is to emphasize on the importance of considering herpes simplex infection in pregnant women who present with acute liver failure, and the importance of early administration of antiviral therapy.

A 7-month-old boy presented with gastrointestinal disturbance, mild neurologic deficit of the left lower extremity and levo-scoliosis of the thoracic spine. Magnetic resonance imaging demonstrated a large intramedullary lesion involving the thoracic spine, from level T1 to T11. Histologic analysis showed a glial tumor with fibrillary processes arranged in radial pattern around mucoid fibrovascular cores with a high proliferative index (focally up to 80%) and prominent vascular endothelial hyperplasia. These findings were consistent with an anaplastic myxopapillary ependymoma. Subtotal resection was performed via a T3-T10 laminoplasty. A ventricular shunt was placed, and the patient subsequently received chemoradiation therapy. To date, this is the second case of a myxopapillary ependymoma with high-grade anaplastic features and the first case in an infant reported in the literature.

Phosphoglycerate kinase (PGK) deficiency affects three different organs: red blood cells (RBC), the central nervous system, and muscles. Next-generation sequencing identified a hemizygous PGK1 mutation (p.V217I) in a 16-year-old Japanese male patient presenting with intellectual disability and episodes of muscle weakness of unknown etiology. Enzymatic analysis demonstrated slightly lower RBC-PGK activity and compensatory increases of other glycolysis enzymes. This is the first PGK1 mutation found through next-generation sequencing.

An 18-year-old gentleman with a history of recurrent tonsillitis presented to the emergency room complaining of worsening sore throat. He was found to have a peritonisillar abscess, and imaging revealed a non-occlusive left internal jugular vein thrombosis. Lemierre's syndrome is a rare, potentially fatal condition characterized by internal jugular vein thrombosis with septicemia following an acute oropharyngeal infection. While anticoagulation is the mainstay of treatment of deep venous thromboembolism (DVT) and pulmonary embolism (PE), the use of therapy is controversial in septic thrombophlebitis. This is counterintuitive since a common reported complication is pulmonary emboli. Early in the course of thrombophlebitis, while the thrombus is firmly attached, antibiotics may be all that is necessary to treat the condition.

We present here a systemic lupus erythematosus (SLE) related biochemically silent pancreatitis which was assessed via computed tomography in a 35-year-old woman. A patient with a twelve-year history of SLE presented with exacerbation of symptoms of the basic disease, with SLE Disease Activity Index > 15. She was referred to inpatient care. Dosage of corticosteroid and azathioprine for SLE was increased; subclinically and biochemically silent pancreatitis had developed, and was not diagnosed within an appropriate time. On the 15th hospital day, the patient died due to multisystem organ failure, which was defined as a consequence of clinically and biochemically silent pancreatitis in systemic lupus erythematosus.

This case report describes a case of Sturge-Weber syndrome reported for unilateral gingival enlargement and bleeding from gingiva in maxillary left region. Initial treatment in the form of scaling and root planing was done but recurrence was observed after one year of follow up. Instead of performing conventional surgery, an alternative conservative treatment was planned in the form of cryotherapy with the help of closed nitrous oxide probe. Seeing the satisfactory results obtained, cryotherapy can be suggested as an atraumatic, bloodless and effective chair side procedure for treating vascular gingival enlargement.

China has the world's largest population of people with rare diseases. However, defining rare diseases remains a challenge in China. Over the past few decades, several definitions have been proposed but they have yet to be agreed to by all stakeholders. To overcome this impasse, a list of several rare diseases has recently been created. This rare disease list might be used in place of a prevalence-based definition, especially in healthcare policy-making.

Cystic fibrosis is deemed to be uncommon in India. The presentation is usually in the childhood although more cases are now being recognized in adolescence and adulthood. We report a case of an adolescent male who had been treated for recurrent pulmonary infections and received anti-tubercular therapy for a possible diagnosis of sputum negative pulmonary tuberculosis and was evaluated for steatorrhea. The presence of pancreatic exocrine insufficiency along with pancreatic lipomatosis suggested the diagnosis of cystic fibrosis.