Intractable & Rare Diseases Research
Online ISSN : 2186-361X
Print ISSN : 2186-3644
ISSN-L : 2186-3644
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Reviews
  • Sayantan Banerjee, Nitin Gupta, Parul Kodan, Ankit Mittal, Yogiraj Ray ...
    2019 Volume 8 Issue 1 Pages 1-8
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: January 31, 2019
    JOURNALS FREE ACCESS

    Nipah virus, an enveloped ribonucleic acid virus, has been a major cause of encephalitis out- breaks with high mortality, primarily in the Indo-Bangladesh regions. Except for the first outbreak in Malaysia-Singapore, which was related to contact with pigs and the outbreak in Philippines associated with horse slaughter, most other outbreaks have affected the Indo- Bangladesh regions. The Indo-Bangladesh outbreaks were associated with consumption of raw date palm sap contaminated by fruit bats and had a very high secondary attack rate. The patient usually presents with fever, encephalitis and/or respiratory involvement with or without thrombocytopenia, leukopenia and transaminitis. Diagnosis can be confirmed by isolation and nucleic acid amplification in the acute phase or antibody detection during the convalescent phase. Treatment is mostly limited to supportive care and syndromic management of acute encephalitis syndrome. Ribavirin, m102.4 monoclonal antibody and favipiravir are the only anti-virals with some activity against Nipah virus. Standard precautions, hand hygiene and personal protective equipments are the cornerstone of comprehensive infection prevention and control strategy. With the recent outbreaks affecting newer geographical areas, there is a need for physicians to be aware of this disease and keep abreast of its current detection and management strategies.

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  • Junren Lu, Zhenjun Yao, Yi Yang, Chi Zhang, Jian Zhang, Ying Zhang
    2019 Volume 8 Issue 1 Pages 9-13
    Published: February 28, 2019
    Released: March 14, 2019
    JOURNALS FREE ACCESS

    Facioscapulohumeral muscular dystrophy (FSHD) also known as Landouzy-Dejerine disease, is an autosomal-dominant disorder of the skeletal muscles with the name according to the various muscle groups it affects: the face, shoulders and upper arms. It is the third most common genetic degenerative disorder of the skeletal muscles without specific patterns in all the affected individuals. At present there is no cure for the disease but numerous management strategies are available to improve the quality of life and prevent further degeneration of various muscle groups. This review aims to provide an insight on the management strategies for FSHD patients including both lifestyle and medical intervention.

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Brief Reports
  • Felix Claverie-Martin, Amelia Trindade, Noriela C. Garcia-Gonzalez, Al ...
    2019 Volume 8 Issue 1 Pages 14-19
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: January 31, 2019
    JOURNALS FREE ACCESS

    Nail-patella syndrome (NPS) is a rare autosomal dominant disease characterized by developmental defects of dorsal limb structures, the kidney, and the eye, that manifest as dysplastic nails, hypoplastic or absent patella, elbow dysplasia, iliac horns, glomerulopathy, and adult-onset glaucoma, respectively. This disorder is inherited in an autosomal dominant mode and is caused by heterozygous loss-of-function mutations in the LMX1B gene, which encodes the LIM homeodomain transcription factor LMX1B. In this study, we report the clinical findings of a Spanish family, from the Canary Islands, with three affected members who displayed varying phenotypes. DNA sequence analysis identified a novel heterozygous missense mutation in LMX1B, c.305A>G, p.(Y102C), that segregated with the disease. The tyrosine residue affected by the mutation is highly conserved in evolution, and is located in the LIM-A domain, next to one of the cysteine residues involved in zinc binding, suggesting that p.(Y102C) affects LMX1B function by disturbing its interactions with other proteins. Our results expand the mutation spectrum of LMX1B and provide insight into the molecular mechanisms of NPS pathology.

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  • Saori Yamada-Kanazawa, Yukino Tasaki, Ikko Kajihara, Ryoko Sakamoto, S ...
    2019 Volume 8 Issue 1 Pages 20-23
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: February 25, 2019
    JOURNALS FREE ACCESS

    Extramammary Paget's disease (EMPD) is a rare skin malignant tumor. The prognosis of EMPD with distant metastasis is poor, however an effective therapy has not yet established. Recently, EpCAM (epithelial cell adhesion molecule, CD326) has attracted attention as both prognostic marker and therapeutic target in several cancers. Besides, EpCAM is an important surface marker of circulating tumor cell (CTC) in the collection of CTC. Thus, the purpose of our study was to examine the expression levels of EpCAM and evaluate the correlation between its intensity of EpCAM and the clinical characteristics of EMPD. The expression of EpCAM in EMPD was examined using immunohistochemistry. Skin samples were obtained from 32 patients with EMPD. We found that almost all EMPD tissues (90.6%, 29/32) were positive for EpCAM. Furthermore, the staining intensity of EpCAM protein negatively correlated with the presence of distant metastasis. Overexpression of EpCAM in EMPD cells suggests that EpCAM may be a novel therapeutic target and the research of CTC may be newly developed in EMPD. Based on these findings, EpCAM may be a meaningful molecule in EMPD.

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  • Durval Batista Palhares, Deborah Ribeiro Nascimento, Marilene Garcia P ...
    2019 Volume 8 Issue 1 Pages 24-28
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: February 22, 2019
    JOURNALS FREE ACCESS

    Fibrodysplasia ossificans progressiva (FOP) is a rare, intractable and devastating genetic connective tissue disorder characterized by progressive ectopic ossification in the soft tissues and skeleton. Three patients, one teenage girl (P1), one male adult (P2) and one male child (P3), were studied and treated with FOPCON (combined formulation of 14 mg of propranolol and 250 mg of ascorbic acid), given three times per day. P1 started treatment in March 2012, P2 in October 2012 and P3 in July 2015. The clinical follow-up of these three patients, before initiating treatment with FOPCON, showed that FOP flare-ups used to occur frequently and that under FOPCON therapy, none of these patients had flare-ups. The striking feature of this treatment with FOPCON, is that, all three cases suffered accidental falls with documented injures until complete healing and that where major flare-ups should occur, injures or sequels, there was none. The present clinical observation shows that ascorbic acid plus the nonspecific beta blocker propranolol can be effectively useful, when administered previously and continually, in the prophylaxis of FOP flare-ups, especially for accidental falls. In this regard, FOPCON could be a prophylactic aid in cases of surgery of patients with FOP, hoping that it may benefit patients from having the severe sequels, characteristic of heterotopic bone formation. All three patients reported, to date, they no longer had flare-ups nor heterotopic ossification and showed normal scar healing.

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Case Reports
  • María-Teresa Pérez-Sanz, Eva Cervilla-Muñoz, Jaime Alonso-Muñoz, Almud ...
    2019 Volume 8 Issue 1 Pages 29-35
    Published: February 28, 2019
    Released: March 14, 2019
    JOURNALS FREE ACCESS

    Retroperitoneal fibrosis (RPF) is a rare disease characterized by chronic inflammation and periaortic fibrosis that affects retroperitoneal structures and often entraps the ureters. The idiopathic form has an incidence of 0.1-1.3/100,000 person-years. A substantial percentage of patients with idiopathic retroperitoneal fibrosis (IRF), as well as patients with orbital pseudotumor, is associated with IgG4-related disease (IgG4-RD). It is not clear what percentage of IRF is related to the spectrum of the IgG4-RD or if both represent different stages of the same disease (especially in those cases with extra-retroperitoneal involvement). Histopathological features such as storiform fibrosis, obliterative phlebitis and tissue infiltration of IgG4-positive plasma cells (ratio IgG4+/IgG higher than 0.4) are essential to identify this association. Extra-retroperitoneal manifestations are often presented among patients with IgG4-related RPF. About 90% of cases of IRF have a good prognosis, with adequate response to treatment. We report a case of a 59-year-old woman with history of past occupational asbestos exposure and smoking habit. She was diagnosed with RPF, periaortitis and orbital pseudotumor, without histopathologic or serologic features of IgG4-related disease. This could be related to the fact that the biopsy was done in a place with scarce inflammatory activity but high fibrosis. We want to emphasize the usual need to perform several biopsies or to be guided by positron emission tomography (PET-CT) in order to achieve a histopathological confirmation. Our case differs from the main IgG4 international cohorts in the involvement of the retroperitoneum, aorta and eye, whereas the usual involvement includes liver, pancreas, lymph nodes and salivary glands. Our patient had lower IgG4 serum levels than those described in the international cohorts. However, they were similar to those of the Spanish population.

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  • Garima Jain, Chandan Kumar, Pankaj Meena, Angel Rajan Singh, Virendra ...
    2019 Volume 8 Issue 1 Pages 36-42
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: February 05, 2019
    JOURNALS FREE ACCESS

    Hydatid disease is a parasitic infestation caused by Echinococcus, most commonly Echincoccus granulosus. Liver is the most common location followed by lungs. Hydatid involvement of gall bladder is a very rare entity, which masqueraded as gall bladder cancer. Here, we attempt to highlight the relevance of this rare disease and discuss this unique case of a 60-year-old male, who presented with gall bladder mass, abdominal pain, and vomiting. The patient was eventually diagnosed as Hydatid disease. The patient has been treated on medical management and has shown improvement. The manuscript has discussed diagnosis and management of disease along with review of literature.

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  • Manish Chandra Choudhary, Vijeta Bajpai, Lovkesh Anand, Ekta Gupta
    2019 Volume 8 Issue 1 Pages 43-47
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: January 31, 2019
    JOURNALS FREE ACCESS

    Hepatitis E is a serious public health problem in developing countries. Most of the patients with Hepatitis E virus (HEV) infection present with typical acute hepatitis symptoms. However, in few patients it may lead to complications such as liver failure and extrahepatic symptoms. One of the rare extrahepatic presentations of this infection is neurological complications such as Guillain-Barré syndrome (GBS) which is observed in 5.5% of HEV infected patients (mainly in developed countries). Moreover, only genotype (gt) 3 HEV was found in association with GBS among patients in developed countries whereas molecular characterisation of HEV cases detected from developing countries have not been reported till now. Here, we are reporting a case of GBS as an extrahepatic complication of HEV associated with gt1 identified by molecular characterization by performing PCR of open-reading frame 2 (ORF2) region of HEV. Phylogenetic analysis by maximum likelihood method revealed that HEV gt1 case reported in this paper rooted closely with other HEV gt1 samples from South-Asian countries with high bootstrap values indicative of fully resolved tree.

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  • Azka Latif, Vikas Kapoor, Erin Simmons, Jai Parekh, Venkata Andukuri
    2019 Volume 8 Issue 1 Pages 48-51
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: January 31, 2019
    JOURNALS FREE ACCESS

    One of the most common cause of arbovirus encephalitis in the United States of America (USA) is West Nile virus (WNV). In immunocompetent hosts, 70-80% of infected individuals have subclinical disease. However, in less than 1% of people infected by WNV it can become fulminant neuroinvasive disease associated with neurological morbidity. Herein, we discuss a case of neuroinvasive WNV disease with non-specific symptoms in an immunocompetent young female in Omaha. Our patient survived the acute phase of WNV encephalitis but has extended recovery to daily functioning. We also reviewed literature on WNV cases in immunocompetent individuals and to the best of our knowledge only 3 cases have been reported to date. The difference between reported cases and our case is her younger age, bilateral upper and lower extremity paralysis, 30 day hospitalization with significant morbidity leading to a prolonged stay at rehabilitation facility with residual cognitive and gross motor impairment. Usually WNV is not considered a differential in immunocompetent individuals which leads to delay in diagnosis, management and therefore increases mortality and morbidity. Therefore purpose of our case report is to raise awareness of atypical presentations of WNV infection in immunocompetent individuals in non-endemic area to emphasize the importance of early diagnosis and management.

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  • Samuel Asanad, Elana Meer, Jack J. Tian, Michele Fantini, Marco Nassis ...
    2019 Volume 8 Issue 1 Pages 52-55
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: January 31, 2019
    JOURNALS FREE ACCESS

    The purpose of the present article was to evaluate the previously unreported vascular alterations in Leber's Hereditary Optic Neuropathy (LHON) 3460 mitochondrial DNA (mtDNA) mutation. Among the three primary mtDNA mutations, namely 11778, 14484, and 3460, LHON 3460 is the most rare and historically recognized as having the poorest visual prognosis. Optical coherence tomography angiography (OCTA) is a novel imaging modaility providing high-resolution microcirculation maps and enhancing visualization of the optic disc and peripapillary capillary beds. We herein exploit the advantages of OCTA, for the first time, to assess the optic nerve head and peripapillary microvasculature changes in an affected patient and compare these vascular changes with an asymptomatic carrier for LHON 3460, serving as a control. Vascular changes in LHON 11778 and 14484 have classically shown microvasculature attenuation localized specifically to the temporal peripapillary quadrant. In the present case, however, OCTA in LHON 3460, the most severe of the three mutational subtypes, illustrated significant vascular attenuation involving the nasal peripapillary region in addition to the temporal peripapillary microvascular changes classically seen in LHON. Our findings suggest that vascular measures may serve useful for objectively assessing mitochondrial disease. Further OCTA studies involving the nasal peripapillary region may be warranted to further understand vascular pathogenesis in LHON.

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  • Reiko Shibata, Ryo Orii, Rie Ako
    2019 Volume 8 Issue 1 Pages 56-59
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: February 22, 2019
    JOURNALS FREE ACCESS

    Hemophilia is an X-linked recessive inherited coagulation disorder. We report the anesthesia management of a hemophilia patient who underwent arthroscopic ankle arthrodesis after living-donor liver transplantation due to cirrhosis. The 35-year-old male patient with hemophilia B was diagnosed with cirrhosis due to hepatitis C virus at the age of 23 years and underwent biologically-related partial liver transplantation at the age of 29 years. As a result, the activity of factor IX activity became normal and blood product treatment became unnecessary, but the patient required long-term immunosuppression. Perioperative coagulation factor activity monitoring was performed and an immunosuppressive drug that had been preoperatively administered were continued. General anesthesia was administered by inhalation. There was no significant fluctuation in perioperative factor IX activity. This case illustrates that even in patients with hemophilia B after living-donor liver transplantation undergoing an orthopedic surgical procedure, anesthesia management can safely be performed without perioperative coagulation factor replacement.

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  • Christian Mario Amodeo Oblitas, Francisco Galeano-Valle, Neera Toledo- ...
    2019 Volume 8 Issue 1 Pages 60-66
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: February 22, 2019
    JOURNALS FREE ACCESS

    Behçet's Disease (BD) is a rare, chronic and recurrent inflammatory multisystemic condition of unknown origin that can affect any tissue. The vascular system is involved in 5-40% of cases of BD, including venous and arterial beds and it has a relapsing course. Budd-Chiari syndrome (BCS) is a rare complication of BD with a frequency of < 5% among patients with vascular involvement and is more frequent in men (89.5%). Two clinical presentation groups of BCS related to BD have been described: the "symptomatic" form and the "silent" form. We present a case of BD in a young woman presented as symptomatic severe BCS with rapid progression of coagulopathy reaching a spontaneous INR of 1.74 and increased ascites by ultrasound control. BD was confirmed through clinical history. The patient was treated with a high-dose pulse of corticosteroids and cyclophosphamide with a strikingly favorable response in the first forty-eight hours. Although several studies have demonstrated a survival improvement with the use of transjugular intrahepatic portosystemic shunt in patients with severe BCS, it was discarded due to the lack of evidence of this procedure in patients with BD and the fact that it could trigger a vascular pathergy phenomenon. Vascular BD should be suspected in recurrent venous and/or arterial thrombosis since it is associated with high morbidity and mortality. Immunosuppressive treatment is critical for the management of vascular involvement in BD. However, the role of anticoagulation is debatable. We suggest an algorithm for the management of BCS associated with BD.

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  • Hussein Algahtani, Bader Shirah, Raghad Algahtani, Mohammad H. Al-Qaht ...
    2019 Volume 8 Issue 1 Pages 67-71
    Published: February 28, 2019
    Released: March 14, 2019
    JOURNALS FREE ACCESS

    Episodic ataxia is a genetically heterogeneous neurological condition characterized by spells of incoordination and imbalance, often associated with progressive ataxia. Episodic ataxia type 2, caused by calcium voltage-gated channel subunit alpha1 A (CACNA1A MIM: 601011) mutation, is the most common form of episodic ataxia. It is characterized by recurrent attacks of imbalance associated with interictal nystagmus lasting hours to days and triggered by emotional stress or exercise. In this article, we report a novel heterozygous intronic variant c.5743+14A>G in the CACNA1A gene in a Saudi family. To the best of our knowledge, this variant has not been described in the literature or reported in public mutation databases. This report indicated that acetazolamide is not beneficial, and it may be even harmful to patients with episodic ataxia type 2 if used in later stages. In addition, treatment with 4-aminopyridine did not show any efficacy to improve walking or balance in our patient, which indicates the importance of early initiation of therapy before the later stages of the disease. Further research is needed to explore potential treatments for this challenging disease.

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  • Somprakash Dhangar, Seema Korgaonkar, Babu Rao Vundinti
    2019 Volume 8 Issue 1 Pages 72-77
    Published: February 28, 2019
    Released: March 14, 2019
    [Advance publication] Released: February 25, 2019
    JOURNALS FREE ACCESS

    Trisomy 9 including mosaic and partial trisomy is less frequently seen chromosomal abnormality in live born children. The pure or partial trisomy 9 frequently been reported in prenatal diagnosis and product of conception. However few studies reported partial trisomy 9 in live born children. In addition data on genotype and phenotype correlation of partial trisomy is not well understood except few case reports. Here we report a case of partial trisomy 9 and monosomy 14 with a 46,XY,der(9)t(9;14)(q22.1;q11.2)pat,-14 karyotype in a 5-year old dysmorphic child. The proband was confirmed as trisomic for 9pter->9q22.1 and monosomic for 14pter->q11.2 due to paternal t(9;14)(q22.1;q11.2) balanced translocation using a combination of conventional and molecular cytogenetic (fluorescence in situ hybridization, array-comparative genomic hybridization) techniques. The clinical features similar to pure trisomy 9 is due to duplication of the large region of chromosome 9. However, the present report of partial trisomy 9 and monosomy 14 is a novel case report and showing comparatively longer survival which have not been previously reported in the literature. The parent of the proband was counseled for the future pregnancies.

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Letter
  • Qianli Ren, Jianbin Wang
    2019 Volume 8 Issue 1 Pages 78-79
    Published: February 28, 2019
    Released: March 14, 2019
    JOURNALS FREE ACCESS

    Rare diseases are an important public health issue and a challenge to healthcare. Over the past few years, China has actively worked to improve rare disease care and orphan drugs for rare diseases, but many challenges still remain. In order to further promote measures to combat rare diseases, the "National Network to Collaborate on Diagnosis and Treatment of Rare Diseases" was established by the National Health Commission of the People's Republic of China on February 12, 2019. This network for collaboration consists of 324 hospitals nationwide, and its aim is to set up a practical mechanism for an effective alliance by different tiers of the healthcare system. The strategy for collaboration includes six programs: i) to establish a mechanism for collaboration, ii) to implement standards of care, iii) to enhance quality control, iv) to ensure the supply of drugs, v) to set up a registry, and vi) to enhance clinical research. These programs will play a pivotal role in combating rare diseases in the future and eventually achieving the goal of creating a proper and consistent mechanism to treat and manage rare diseases.

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