Vol 4-3 Case Report

Malignant Degeneration into Chondrosarcoma of Multiple Exostosis Disease: The First Senegalese Case Report

Moustapha Niasse1*, Baïdy Sy Kane2, Abdou Majib Gaye3, El Hadji Modou Ndiaye2, Ibrahima Faye4, Maïmouna Sow2, Tafsir Ngary Ka2, Alioune Badara Diallo2, Atoumane Faye2, Saïdou Diallo1

1Department of Rheumatology, Aristide Le Dantec Teaching Hospital; Cheikh Anta DIOP University of Dakar, Senegal

2Department of Internal Medicine, Aristide Le Dantec Teaching Hospital; Cheikh Anta DIOP University of Dakar, Senegal

3Department of Anatomy and pathology, Aristide Le Dantec Teaching Hospital; Cheikh Anta DIOP University of Dakar, Senegal

4Department of Radiology, Aristide Le Dantec Teaching Hospital; Cheikh Anta DIOP University of Dakar, Senegal

DOI: 10.29245/2572-9411/2019/3.1185 View / Download Pdf
Vol 4-3 Case Report

Osteopoikilosis: Two Senegalese Case Reports

Moustapha Niasse1*, Baïdy Sy Kane2, Yetna Tcheindah1, Kaba Condé3, Coumba Diouf1, Léra Géraud Akpo4, Ibrahima Faye4, Saïdou Diallo1

1Department of Rheumatology, University Hospital Aristide Le Dantec of Dakar, Senegal

2Department of Internal Medicine, University Hospital Aristide Le Dantec of Dakar, Senegal

3Department of Rheumatology, University Hospital Ignace Deen of Conakry, Guinea

4Department of Radiology, University Hospital Aristide Le Dantec of Dakar, Senegal

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Vol 5-1 Mini Review

The Known Unknowns: Missing Pieces in in vivo Models of Fragile X Syndrome

Pushkar Kulkarni*, Aarti Sevilimedu*

Centre for Innovation in Molecular and Pharmaceutical Sciences (CIMPS), Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, Telangana, 500046, India

Fragile X Syndrome (FXS) is a rare disease and the leading monogenic cause of Autism Spectrum Disorders (ASD). It is caused by the silencing of the Fragile X mental retardation (FMR1) gene and the subsequent reduction or loss of fragile X mental retardation protein (FMRP). The clinical effects seen in FXS patients are several and highly variable making it difficult to model them in a single model or even one organism. Furthermore, several human behaviours can be measured only through surrogate endpoints in animals. Therefore, it has been challenging to develop in vivo models of FXS for drug discovery.

This review endeavours to consolidate the information on all available in vivo models for FXS specifically with a focus on their suitability for drug development, with the objective of identifying gaps and potential solutions. To do so, we have summarised the major clinical characteristics and possible mechanisms underlying clinical phenotypes associated with FXS and other disorders that arise from abnormalities in the FMR1 locus, such as fragile-X associated tremor/ataxia syndrome (FXTAS), fragile-X-associated neuropsychiatric disorders (FXAND) including ASD and fragile x-associated primary ovarian insufficiency (FXPOI). We then connect clinical features to phenotypes observed in available in vivo FXS models where possible, covering a wide range of organisms from primates, rats, mice, zebrafish, fruit fly and zebra finches. For each model organism, we list the technology of model creation, phenotypes/assays, mechanistic basis of disease manifestation and specific advantages or disadvantages of the model in the context of drug discovery.

Finally, we have highlighted the missing pieces in FXS modelling and propose strategies to address them, considering aspects of modelling spectrum disorders, repeat expansion and silencing, new functions of FMRP and identification of efficacious treatments.

DOI: 10.29245/2572-9411/2020/1.1190 View / Download Pdf
Vol 5-2 Original Research Article

Prolactinoma as a Cause of Persistent Hyperprolactinemia in 6-Pyruvoyl-tetrahydropterin synthase Deficiency

Zainab Almasseri1, Manal Nicolas- Jilwan2, Ahmad Khaled Almadani1, Mohammad Al-Owain1,5, Rousseau Gama3,4, Raashda Ainuddin Sulaiman1,5*

1Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

2Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

3Blood sciences, The Royal Wolverhampton NHS trust, Wolverhampton, UK

4School of Medicine and Clinical Practice, Wolverhampton University, UK

5College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency results in depletion of the brain neuro-transmitters serotonin and dopamine. Since dopamine is the physiological inhibitor of pituitary prolactin secretion, hyperprolactinemia is common in patients with PTPS deficiency. Serum prolactin concentrations are used for the monitoring and optimization of L-Dopa therapy. We report three adult patients with PTPS deficiency who had persistent hyperprolactinemia unresponsive to high dose L-Dopa therapy, and pituitary imaging confirmed microadenoma. In the presence of prolactinoma, serum prolactin is an unreliable tool for treatment monitoring in these patients. This report emphasizes the need to exclude other causes of hyperprolactinemia including prolactinoma, in patients who are compliant with optimized L-Dopa treatment and their prolactin levels remain significantly high.

DOI: 10.29245/2572-9411/2020/2.1191 View / Download Pdf
Vol 5-2 Research Article

Geographic Distribution of Inflammatory Breast Cancer and Non-Inflammatory Breast Cancer in Gharbiah, Egypt

An Nguyen1, Amr S. Soliman2*, Ahmed Hablas3, Mohamed Ramadan3, Ibrahim Seifeldin3

1Milken Institute School of Public Health, The George Washington University, Washington, DC, USA

2CUNY School of Medicine, New York, NY, USA

3Gharbiah Cancer Society, Tanta, Gharbiah, Egypt

BACKGROUND: Inflammatory Breast Cancer (IBC) is a rare but aggressive form of breast cancer, constituting about 1-5% of breast cancers in the U.S. but about 11% in Egypt. The etiology of IBC is unknown, but the distribution of residence of IBC and non-IBC patients may provide clues to the disease risk factors. Therefore, we investigated the geographic distribution of IBC and non-IBC in the province of Gharbiah, Egypt.

METHODS: All breast cancers diagnosed during the period of January 2009 to December 2010 were retrieved from the Gharbiah Population-based registry. IBC cases were obtained from a case-control study conducted in the same region and period. Incidence rates were calculated for IBC and non-IBC for each of the eight districts and their rural/urban regions.

RESULTS: The incidence of IBC was higher in rural than urban areas, in contrast to the incidence of non-IBC. Clustering of IBC and non-IBC was observed more in urban than in rural areas. IBC clusters were detected in 7 of the 8 urban areas of Gharbiah, with the highest incidence identified in urban Kafr El-Zayat. Non-IBC clusters were distributed in all 8 urban areas of Gharbiah without clustering, with highest incidence is identified in urban Tanta.

CONCLUSION: Our results showed different geospatial distributions of IBC and non-IBC relative to the regional environmental exposures. Future studies should explore specific environmental exposures that may contribute to the geographic distribution of IBC and non-IBC in the region to further explore the etiology of IBC and non-IBC.

DOI: 10.29245/2572-9411/2020/2.1192 View / Download Pdf
Vol 5-2 Research Article

A Careful Interpretation of the Audiometry may contribute to the Diagnosis of Alport Syndrome: A Pilot Study

Claudio Alves Andrade Cardoso#, Danilo Euclides Fernandes#*, Michelle Tiveron Passos Riguetti, Gianna Mastroianni Kirsztajn

Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo - SP, 04021-001, Brazil

INTRODUCTION: Hearing loss is a typical finding in Alport syndrome (sAlport) caused by a genetic defect in the type IV collagen synthesis. Depending on the criteria, these individuals may be diagnosed with normal hearing.

OBJECTIVE: To compare the prevalence of hearing loss according to different criteria – World Health Organization, WHO; Global Burden Disease, GBD and Clark – in patients with sAlport and segmental and focal glomeruloesclerosis (FSGS).

MATERIALS AND METHODS: This is a cross-sectional pilot study. Pure-tone audiometry was carried out in patients with sAlport and FSGS (glomerulopathy which was selected as a control group).

RESULTS: We assessed 13 patients (6 with sAlport and 7 with FSGS). Under the WHO criteria, no patient had hearing loss. The prevalence of hearing loss was similar according to GBD criteria (16.67% and 14.29% in the sAlport and FSGS groups, respectively). Clark's criteria, instead, revealed a higher prevalence of hearing loss in the sAlport group (66.67%) vs. FSGS (28.57%).

CONCLUSION: The prevalence of hearing loss in the sAlport group varied depending on the criteria (from nonexistent to 67%). We consider that a critical evaluation of the hearing thresholds may help physicians to early detect minimal hearing impairment even though the report says, “normal hearing”.

DOI: 10.29245/2572-9411/2020/2.1193 View / Download Pdf
Vol 5-2 Short Communication

Renal Ultrasound contributes to Fabry Disease Diagnosis

Rodrigo F.C. Azambuja Neves1,2, Patrícia Varela3, Danilo Euclides Fernandes1*, Michelle T. P. Riguetti1, Simone Geraldini1, Gustavo Ferreira da Mata1, Carmen Mendes4, Ana Maria Martins4, João Bosco Pesquero3, Gianna Mastroianni Kirsztajn1*

1Section of Glomerulopathies, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil

2Radiology Service of Hospital do Rim, São Paulo, Brazil

3Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil

4IGEIM (Innate Errors of Metabolism), Federal University of São Paulo, São Paulo, Brazil

Introduction: Renal impairment in Fabry disease is widely known, but the occurrence of renal cysts as a manifestation of the disease should still be highlighted among radiologists and other physicians.

Objectives: To compare the presence of parapelvic cysts between Fabry disease and other causes of chronic kidney disease (CKD).

Methods: We evaluated demographic, clinical and laboratory data, as well as kidney ultrasound (US) findings in 91 patients with Fabry disease (n=37) and different glomerulopathies (n=54).

Results: Both groups were similar in age (p = 0.29), gender (p = 0.98), eGFR (p = 0.10) and CKD stages (p = 0.19).Presence of parapelvic cysts differed significantly between those two groups (p < 0.0001 in right and left kidneys; Cohen’s h = 1.15). When present, diameters of the parapelvic cysts were similar. Both groups had signs of CKD such as corticomedullary undifferentiation. None of the mutations we found in GLA gene was associated with a higher prevalence of parapelvic cysts.

Conclusions: When compared to different glomerulopathies, parapelvic cysts were more frequently found in Fabry disease despite age, gender and stage of CKD. Parapelvic cysts on ultrasound can raise suspicion on Fabry disease in patients with kidney disease of unknown etiology especially in the context of a familial nephropathy.

DOI: 10.29245/2572-9411/2020/2.1195 View / Download Pdf
Vol 5-2 Research Article

The Relationship Between Sleep and Physical Activity Level in Barth Syndrome: A Cross-Sectional Analysis

Neil A. Judd*, Hannah S. Calhoun, Virginia Chu, Stacey Reynolds

Virginia Commonwealth University

Barth syndrome (BTHS) is a rare genetic disorder commonly characterized by cardiomyopathy, muscle weakness, abnormal fatigability, and exercise intolerance. Sleep problems have been identified informally within the BTHS community though it has never been systematically studied. This study aimed to (1) objectively quantify sleep in males with BTHS, (2) examine the relationship between sleep and physical activity levels, and (3) examine age-related trends in data. Twenty participants (7 adults and 13 children) with BTHS completed the study. Each participant wore an Actigraph GT9X activity tracker and completed a sleep diary for 14 consecutive days. Energy expenditure was calculated at various time periods: early morning, late morning, early afternoon, late afternoon, early evening, and late evening. Generalized Linear Models support statistically significant interactions between physical activity levels throughout the day and sleep parameters (sleep latency, efficiency, and nighttime awakenings). Trend analysis showed children had a longer sleep latency, higher sleep efficiency, and more nighttime awakenings than adults and were more active overall. Some of the findings in our study contradict current literature pointing to a relationship between sleep and physical activity levels in the typical population. This suggests other factors may impact decreased sleep in BTHS and warrants future studies into the causes of decreased sleep and the relationship to physical activity in this population.

DOI: 10.29245/2572-9411/2020/2.1194 View / Download Pdf
Vol 5-2 Short Communication

Epidemiology of the Global Fibrodysplasia Ossificans Progressiva (FOP) Community

Moira Liljesthröm1, Robert J. Pignolo2, Frederick S. Kaplan3*

1President of Fundación FOP, Argentina; Argentine Representative to the International President’s Council of the International Fibrodysplasia Ossificans Progressiva Association (IFOPA), Buenos Aires, Argentina

2Department of Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA

3The Departments of Orthopaedic Surgery, Medicine and The Center for Research in FOP & Related Disorders, The Perelman School of Medicine of The University of Pennsylvania, Philadelphia, PA 19104, USA

Background: Fibrodysplasia Ossificans Progressiva (FOP) is an ultrarare disease, but the geographic distribution and regional prevalence of the condition are unknown. This study was undertaken to determine the emerging global population of FOP patients who were associated with a regional, national or international FOP organization.

Results: This study interrogated the patient registration database of the International Fibrodysplasia Ossificans Progressiva Association (IFOPA) and those of the 16 regional or national FOP organizations in order to assemble a non-redundant worldwide census of patients living with FOP in 2016 who were associated with a pre-identified FOP community. The total registered population of the global FOP community was 834 individuals [445 females (54%), 387 males (46%), 2 unassigned] distributed in 67 countries and six continents. The apparent prevalence of registered and confirmed FOP patients varied substantially from approximately 0.65 per million in North America, 0.47 per million in Western Europe, and 0.27 per million in Latin America, to 0.05 per million in Africa and nearly 0.04 per million in the Asia-Pacific region.

Conclusions: The high variability in apparent prevalence is likely associated with lack of awareness of FOP in under-represented medical communities, delay in achieving the correct FOP diagnosis, lack of supporting regional infrastructure and inability of individuals with FOP to reach a local FOP organization or the international FOP community. Emerging knowledge of the apparent prevalence of FOP can serve as a catalyst for resource allotment; physician, patient and community education and outreach; clinical trial recruitment and global networking to achieve a more globally robust and interconnected FOP community.

DOI: 10.29245/2572-9411/2020/2.1196 View / Download Pdf
Vol 5-3 Case Report

Farber disease: A Fatal Childhood Disorder with Nervous System Involvement

Ichraf Kraoua1,2,3, Thouraya Ben Younes1,2,3*, Virginie Garcia4, Hanene Benrhouma1,2,3, Hedia Klaa1,2,3, Aida Rouissi1,2,3, Thierry Levade4,5, Ilhem Ben Youssef-Turki1,2,3

1Department of Child and Adolescent Neurology. National Institute Mongi Ben Hmida of Neurology. Tunis, Tunisia

2Research Laboratory LR18 SP04. National Institute Mongi Ben Hmida of Neurology. Tunis, Tunisia

3University of Tunis El Manar, Faculty of Medicine of Tunis. Tunis, Tunisia

4Cancer Research Center of Toulouse, INSERM UMR1037 and Université Paul Sabatier, Toulouse, France

5Laboratory of Metabolic Biochemistry, Federative Institute of Biology, CHU Purpan, Toulouse, France

Farber Disease is an autosomal recessive inherited lysosomal storage disorder which is characterized by tissue accumulation of ceramide. It is caused by mutations within ASAH1 encoding for acid ceramidase. It represents a rare condition. Only twenty seven cases have been reported. Seven subtypes of Farber disease have been identified. The clinical presentation is characterized by the appearance of subcutaneous skin nodules, bone and joint deformities, and progressive hoarseness. Neurological symptoms as psychomotor delay or regression, hypotonia, seizures, and peripheral neuropathy were reported in some subtypes of Farber disease. The nervous system involvement is correlated to poor prognosis. In this study, we report on clinical, biochemical and molecular findings of two Tunisian siblings with Farber disease.

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