Intractable & Rare Diseases Research
Online ISSN : 2186-361X
Print ISSN : 2186-3644
ISSN-L : 2186-3644
Current issue
Showing 1-12 articles out of 12 articles from the selected issue
Review
  • Yuelin Ma, Qing Teng, Yiran Zhang, Songyun Zhang
    Type: research-article
    2020 Volume 9 Issue 4 Pages 187-195
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: July 09, 2020
    JOURNALS FREE ACCESS

    Porphyrias are a group of inherited metabolic diseases that include eight types, each of which is caused by a mutation that affects an enzyme of the heme biosynthetic pathway. When an enzyme defect has physiological significance, it leads to overproduction of pathway precursors prior to the defective step. The partial absence of the third enzyme in the heme biosynthetic pathway, porphobilinogen deaminase (PBGD) also known as hydroxymethylbilane synthase (HMBS), results in acute intermittent porphyria (AIP), which affects mainly women. Subjects who had AIP symptoms were deemed to have manifest AIP (MAIP). Clinical manifestations are usually diverse and non-specific. Acute AIP episodes may present with abdominal pain, nausea, and vomiting, and repeated episodes may result in a series of chronic injuries. Therefore, studying the mechanisms of acute and chronic manifestations of AIP is of great significance. This review aims to summarize the possible mechanisms of acute and chronic manifestations in patients with AIP.

    Download PDF (305K)
  • Liyan Ma, Yu Tian, Chenxing Peng, Yiran Zhang, Songyun Zhang
    Type: review-article
    2020 Volume 9 Issue 4 Pages 196-204
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: August 14, 2020
    JOURNALS FREE ACCESS

    Acute intermittent porphyria (AIP) is a dominant inherited disorder with a low penetrance that is caused by mutations in the gene coding for hydroxymethylbilane synthase (HMBS). Information about the epidemiology and molecular genetic features of this rare disorder is crucial to clinical research, and particularly to the evaluation of new treatments. Variations in the prevalence and penetrance of AIP in various studies may due to the different inclusion criteria and methods of assessment. Here, the prevalence and penetrance of AIP are analyzed systematically, and the genetic traits of different populations and findings regarding the genotype-phenotype correlation are summarized. In addition, quite a few studies have indicated that AIP susceptibility was affected by other factors, such as modifying genes. Findings regarding possible modifying genes are documented here, helping to reveal the pathogenesis of and treatments for AIP. The status of research on AIP in China reveals the lack of epidemiological and genetic studies of the Chinese population, a situation that needs to be promptly remedied.

    Download PDF (360K)
  • Lanlan Zhao, Xinyang Wang, Xiaoning Zhang, Xiantao Liu, Ningzhen Ma, Y ...
    Type: review-article
    2020 Volume 9 Issue 4 Pages 205-216
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: August 24, 2020
    JOURNALS FREE ACCESS

    Acute intermittent porphyria (AIP) is an autosomal dominant disease caused by mutations in porphobilinogen deaminase (PBGD), the third enzyme of the heme synthesis pathway. Symptoms of AIP usually manifest as intermittent acute attacks with occasional neuropsychiatric crises. The management of AIP includes treatment of acute attacks, prevention of attacks, long-term monitoring and treatment of chronic complications. Intravenous injection of heme is the most effective method of treating acute attacks. Carbohydrate loading is used when heme is unavailable or in the event of mild attacks. Symptomatic treatment is also needed during attacks. Prevention of attacks includes eliminating precipitating factors, heme prophylaxis and liver transplantation. New treatment options include givosiran (siRNA) to down-regulate ALA synthase-1 (ALAS1) and the messenger RNA of PBGD (PBGD mRNA) delivered to the liver cells of patients with AIP. Long-term monitoring of chronic complications includes regular liver-kidney function and hepatocellular carcinoma (HCC) screening.

    Download PDF (371K)
Original Article
  • Jun-ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Tsuyoshi Ishida, Yuko ...
    Type: research-article
    2020 Volume 9 Issue 4 Pages 217-221
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: August 26, 2020
    JOURNALS FREE ACCESS

    By combining genomic data and brain imaging data, a recent study has identified a novel gene named FAM222A that participates in the formation of amyloid-β (Aβ) plaques and brain atrophy in Alzheimer's disease (AD). FAM222A encodes a 47-kDa protein designated Aggregatin that accumulates in the center of amyloid plaques and physically interacts with Aβ to facilitate Aβaggregation. Aggregatin is expressed predominantly in the central nervous system (CNS) and its levels are increased in brains of the patients with AD and in mouse models of AD. However, at present, the precise cell types that express Aggregatin in the human CNS remain unknown. By immunohistochemistry, we studied Aggregatin expression in the frontal lobe of the patients with AD, Nasu-Hakola disease (NHD), and the subjects who died of non-neurological causes (NNC). We identified the clusters of Aggregatin-positive reactive astrocytes distributed widely in the cerebral cortex of most cases examined. In contrast, small numbers of cortical neurons showed variable immunoreactivities for Aggregatin, whereas microglia and oligodendrocytes did not express Aggregatin. Importantly, amyloid plaques were not clearly labelled with anti-Aggregatin antibody. These results suggest that Aggregatin plays a primarily role in generation of reactive astrocytes in the human CNS.

    Download PDF (1987K)
  • Ana Perdomo-Ramirez, Montserrat Antón-Gamero, Daniela Sakaguchi Rizzo, ...
    Type: research-article
    2020 Volume 9 Issue 4 Pages 222-228
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: October 12, 2020
    JOURNALS FREE ACCESS

    The oculocerebrorenal syndrome of Lowe is a rare X-linked disease characterized by congenital cataracts, proximal renal tubulopathy, muscular hypotonia and mental impairment. This disease is caused by mutations in the OCRL gene encoding membrane bound inositol polyphosphate 5-phosphatase OCRL1. Here, we examined the OCRL gene of two Lowe syndrome patients and report two new missense mutations that affect the ASH domain involved in protein-protein interactions. Genomic DNA was extracted from peripheral blood of two non-related patients and their relatives. Exons and flanking intronic regions of OCRL were analyzed by direct sequencing. Several bioinformatics tools were used to assess the pathogenicity of the variants. The three-dimensional structure of wild-type and mutant ASH domains was modeled using the online server SWISS-MODEL. Clinical features suggesting the diagnosis of Lowe syndrome were observed in both patients. Genetic analysis revealed two novel missense variants, c.1907T>A (p.V636E) and c.1979A>C (p.H660P) in exon 18 of the OCRL gene confirming the clinical diagnosis in both cases. Variant c.1907T>A (p.V636E) was inherited from the patient's mother, while variant c.1979A>C (p.H660P) seems to have originated de novo. Analysis with bioinformatics tools indicated that both variants are pathogenic. Both amino acid changes affect the structure of the OCRL1 ASH domain. In conclusion, the identification of two novel missense mutations located in the OCRL1 ASH domain may shed more light on the functional importance of this domain. We suggest that p.V636E and p.H660P cause Lowe syndrome by disrupting the interaction of OCRL1 with other proteins or by impairing protein stability.

    Download PDF (1502K)
Case Report
  • Wilmar Saldarriaga Gil, Laura Alejandra Ávila Vidal, Manuel Alejandro ...
    Type: case-report
    2020 Volume 9 Issue 4 Pages 229-232
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: August 24, 2020
    JOURNALS FREE ACCESS

    Familial hypertrophic cardiomyopathy (FHCM) is a genetic disease characterized by left ventricle (LV) or interventricular septum hypertrophy. FHCM is a common heart disease (affecting 1 out of 500 individuals) associated with genetic variants in genes related to the sarcomere, including the MYL2 (myosin light chain 2) gene that is affected in 1 to 3% of the cases. As described in this report, the genetic mutation p.Gly87Ala, rs 397516399 in the MYL2 gene is likely pathogenic. Reported here is the case of a 37-year-old Colombian man with asymmetric septal hypertrophic cardiomyopathy and ventricular tachycardia. The man had progressive symptomatology, a family history of FHCM with a dominant inheritance pattern, a mother and 2 brothers with FHCM, and 2 brothers who died suddenly before the age of 35. A molecular panel of 17 genes for hypertrophic cardiomyopathy identified a heterozygous variant, p.Gly87Ala, of the MYL2 gene. This variant can be found in Ensembl, dbSNP, and ClinVar, where it has conflicting interpretations: it either has an uncertain significance or it is likely pathogenic. This is the first report of a Colombian case of FHCM secondary to a mutation in the MYL2 gene, highlighting the importance of molecular diagnosis, genetic counseling, and bioinformatic analysis in these patients.

    Download PDF (562K)
  • Nikolaos S. Salemis
    Type: case-report
    2020 Volume 9 Issue 4 Pages 233-246
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: August 24, 2020
    JOURNALS FREE ACCESS

    Primary neuroendocrine carcinoma of the breast (NEBC) is a very rare occurrence accounting for less than 0.1% of all breast cancers. Typically, the tumor presents with ER- and PgR-positive and HER-2-negative status. Despite its luminal type, NEBC is associated with a more aggressive clinical course and poorer prognosis compared to the other types of invasive breast cancer. Clinical and radiological findings are nonspecific. The most common clinical manifestation is a palpable mass whereas in mammography the tumor most commonly appears as a round or oval mass without spiculated margins. Herein, a very rare case of NEBC is described in an asymptomatic patient who presented with an area of architectural distortion and the presence of microcalcifications that was incidentally detected on a screening mammography. A review of the literature has also been conducted. The diagnosis of NEBC requires a thorough investigation to exclude the possibility of a metastatic neuroendocrine tumor from another site because the two entities require different treatment approaches. Due to the rarity of the disease, the optimal therapeutic approach has not been clearly defined. Surgical resection is the mainstay of treatment. Further research is needed to better understand the molecular characteristics of NEBC and identify novel targeted therapies.

    Download PDF (1166K)
  • Megha Sasidharan, Jinsi Elsa Itty, Ghanta Hinduja, Shabnam Hasna, Deen ...
    Type: case-report
    2020 Volume 9 Issue 4 Pages 247-250
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: September 04, 2020
    JOURNALS FREE ACCESS

    The study reports a case that was responding well to sounds and suddenly stopped hearing following fever. She contracted bacterial meningitis at the age of 5 months and had sought an audiological opinion at the age of 7 years. On evaluation, the objective test results showed normal peripheral hearing, but behaviorally she did not respond to any sounds presented during pure-tone audiometry (PTA). Thus, she was evaluated for higher auditory function using late latency response (LLR) and the responses were absent bilaterally. This confirmed cortical deafness post meningitis. Meningitis can thus also cause cortical deafness in addition to peripheral hearing loss.

    Download PDF (952K)
  • Diego Coletta, Chiara Parrino, Simone Nicosia, Emy Manzi, Giada Pattar ...
    Type: case-report
    2020 Volume 9 Issue 4 Pages 251-255
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: October 09, 2020
    JOURNALS FREE ACCESS

    Primary leiomyoma of the liver (PLL) is a rare benign tumor occurring in immunosuppressed people. From 1926 less than fifty cases are reported in the scientific literature and about half are in immunocompetent patients. Etiology of this kind of lesion is not yet well known. We report a case of primary hepatic leiomyoma in a 60-year-old immunocompetent woman. The patient presented with lipothymia with unexpected vomiting. She underwent an ultrasound (US), and a computed tomography (CT) scan that revealed the presence of a single, solid lesion about 9 cm located between the S5 and S8 segment of the liver. It showed a well-defined, heterogeneous hypodensity with internal and peripheral enhancement and various central hypoattenuating areas and no wash-out in the portal and the late phases. Because of her symptoms and the risk of malignancy, the patient underwent a surgical liver resection. Histological diagnosis was primary leiomyoma of the liver. The patient had an uneventful recovery and was discharged after 7 days. At 30 months follow-up there were no symptoms and no evidence of disease. Leiomyoma of the liver is a rare benign neoplasm of which clinical symptoms are nonspecific and the exact radiological diagnosis still remains a challenge for radiologists. Etiology is still unclear and usually PLL represents an incidental diagnosis. Surgery plays a primary role not only in the treatment algorithm, but also in the diagnostic workout.

    Download PDF (1307K)
  • Abdallah Qasim, Mohamed Mansour, Omar Kousa, Dana Awad, Bader Abuhazee ...
    Type: case-report
    2020 Volume 9 Issue 4 Pages 256-259
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: September 04, 2020
    JOURNALS FREE ACCESS

    Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that was identified in December 2019. The impact of COVID-19 virus on Acquired Immunodeficiency syndrome (AIDS) patients has been reported with variable outcome. We reported a patient that was immunosuppressed by AIDS disease and chemotherapy for cancer who contracted SARS-CoV-2 infection and had a mild disease. We did literature review for the cases published that had human immunodeficiency virus (HIV) infection and COVID-19 disease and analyzed the characteristics and outcomes of the reported cases. Our review yielded three case reports and four case series for patients with HIV infection and COVID-19 disease. The majority of patients had mild disease, and some had critical disease or death. Those who had severe disease usually had other comorbidities. The findings from the case reports and case series indicate that the risk of death or severe disease from COVID-19 in HIV positive patients was lower than observed in the general population, which may indicate a possible protective effect of uncontrolled HIV in preventing the complications associated with the massive inflammatory response.

    Download PDF (357K)
  • Joshua Hendrix, Zhenggang Xiong
    Type: case-report
    2020 Volume 9 Issue 4 Pages 260-262
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: October 09, 2020
    JOURNALS FREE ACCESS

    Pilocytic astrocytomas are tumors of the central nervous system mostly during the first two decades of life. Although they are mostly common in the midline structures of children, pilocytic astrocytoma within the ventricular system of an adult is extremely rare. We report a case of a 38-year old woman with obstructive hydrocephalus secondary to a brain tumor within the third ventricle. On histological examination, the tumor exhibited biphasic growth pattern comprising compacted cellular areas with Rosenthal fibers and loose textured microcystic areas with eosinophilic granular bodies. Mitosis or necrosis was not present. Immunohistochemical studies demonstrated glial fibrillary acid protein (GFAP), Olig2, and ATRX positivity as well as NeuN and EMA negativity. Ki67 labeling index was less than 1%. Molecular studies revealed that there are no isocitrate dehydrogenase (IDH) gene mutation and H3F3A mutation. This clinical presentation along with the histologic and molecular findings is consistent with a pilocytic astrocytoma arising in the third ventricle of this adult brain, which indicates that pilocytic astrocytoma can present as an intraventricular tumor in an adult patient and should be routinely included in the differential diagnosis of intraventricular brain neoplasm.

    Download PDF (1482K)
Letter
  • Nikolaos S. Salemis, Nikolaos Koliarakis, Kyriakos Spiliopoulos, Konst ...
    Type: letter
    2020 Volume 9 Issue 4 Pages 263-265
    Published: October 31, 2020
    Released: November 04, 2020
    [Advance publication] Released: October 09, 2020
    JOURNALS FREE ACCESS

    Primary cutaneous follicle center lymphoma (PCFCL) is defined as a low-grade B-cell non-Hodgkin’s lymphoma, which primarily occurs and remains confined to the skin, without evidence of extracutaneous or systemic involvement at the time of diagnosis. PCFCL affecting the breast skin is an exceedingly rare entity with only two cases reported in the English literature. We present a case of PCFCL affecting the periareolar breast skin and review the relevant literature. Our patient was a 64-year-old female who presented with an erythematous plaque in the periareolar region of the left breast. The diagnosis of PCFCL was confirmed by a biopsy performed with a seven-month delay, as the tumor had been initially misdiagnosed as a benign lesion. The patient was successfully treated with local radiation therapy. PCFCL is an indolent lymphoma associated with an excellent prognosis. For localized lesions, skin-directed therapies mainly consisting of radiation therapy or complete surgical excision are curative therapeutic approaches, while systemic chemotherapy should be reserved for patients with extensive disease. This case highlights the need to consider PCFCL as an important differential diagnosis in patients presenting with non-resolving erythematous breast skin lesions. A timely biopsy should be obtained to avoid delays in the initiation of appropriate treatment.

    Download PDF (639K)
feedback
Top