Danielle H. Bodicoat1, Vincenzo Papa2, Rita Alves1, Angela Arteaga Duarte1, Luca Tofani2

1HEOR Value Hub, Brussels, Belgium

2SIFI S.p.A., 36, Via Ercole Patti, 95025 Aci S. Antonio (Catania), Italy

To describe the evidence for agents with anti-amoebic activity used to treat Acanthamoeba keratitis (AK), two systematic literature reviews (SLRs) were conducted of 1) clinical outcomes for patients with AK and 2) health economic outcomes for patients with AK or microbial keratitis (MK).

The intervention of interest was any agent with anti-amoebic activity administered as eye-drops or orally. The main outcome was clinical resolution. Electronic databases (January 1992-July 2022), conference abstracts (2017-2022), and relevant websites were hand-searched. Risk of bias assessments used external assessment tools. A narrative synthesis was conducted.

The clinical SLR (37 studies; 2043 patients) identified at least 20 studies reporting clinical resolution, best-corrected visual acuity, and corneal surgery; fewer studies reported other outcomes. Treatment regimes, outcome definitions and assessment timing varied markedly between studies. Studies classified as fair or poor quality appeared to underestimate the burden of AK compared with good quality studies. For health economic outcomes (15 studies; 1878 patients), very limited evidence in AK populations was found.

In conclusion, there was a substantial amount of clinical evidence, but scarce economic evidence. Study quality and comparability challenges should be considered when estimating the impact of AK, with substantial between-study heterogeneity limiting options for robust evidence synthesis.

DOI: 10.29245/2572-9411/2023/2.1208 View / Download Pdf

Micaela Pauni1*, Cecilia Mazzuzz2, Guillermo Agosta1

1Department of Child Neurology, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

2Department of Kinesiology, Sanatorio Sagrado Corazón de OSECAC, Buenos Aires, Argentina.

Spinal muscular atrophy (SMA) is a rare, but severe disease, which is characterized by progressive muscular weakness resulting in permanent assisted ventilation before the age of 2. Supportive care used to be the only available treatment. However, relevant progress has been achieved with the approval of nusinersen (an antisense oligonucleotide modulating SMN2 splicing), which changed the disease outcome for many patients. Thus, management of SMA patients requires a multidisciplinary approach with pharmacological and non-pharmacological treatments to provide the necessary supportive care for symptom management, nutritional support and active rehabilitation to optimize muscle function. In this paper we aimed to report the first patient with type 1 SMA in the Latin America region that was able to get off the ventilator without a tracheostomy after an early treatment with nusinersen, continuing to date stable and with no need of ventilatory support.

DOI: 10.29245/2572-9411/2023/1.1207 View / Download Pdf

Paola Krall1,2* Jean Grandy3*, Lillian Bolte4,5*, Jennie Salgado6, Felipe Cavagnaro5, Claudia González7,8, Jose Luis Guerrero2,9*

1 Institute of Medicine, Faculty of Medicine, Universidad Austral de Chile, Valdivia.

2 Department of Pediatrics and Child Surgery, Faculty of Medicine, University of Chile, Santiago de Chile.

3 Department of Nephrology, Hospital Exequiel González Cortés, Santiago de Chile.

4 Department of Nephrology, Hospital Roberto del Río, Santiago de Chile.

5 Department of Pediatrics, Clínica Alemana de Santiago, Santiago de Chile.

6 Department of Nephrology, Hospital CQ Herminda Martín, Chillán.

7 Department of Nephrology, Hospital Sótero del Río, Santiago de Chile

8 Department of Pediatrics, Pontificia Universidad Católica de Chile, Santiago de Chile

9Department of Nephrology, Hospital Dr. Luis Calvo Mackenna, Santiago de Chile.

(*) all these authors contributed equally.


Cystinosis is a rare disease caused by CTNS gene defects. The main clinical presentations are nephropathic infantile cystinosis (NIC) and nephropathic juvenile cystinosis (NJC); both develop chronic kidney disease (CKD) and extrarenal complications. Opportune diagnosis and access to therapy are challenging in developing countries.


To describe the clinical and genetic profile in all cystinosis patients known to be diagnosed in Chile, we performed a retrospective review of the medical records of those patients diagnosed from 1994 to 2022. Age at diagnosis, glomerular filtration rate, metabolic variables, anthropometric values, access to treatment, outcomes, and genetic results were analyzed.


Nine patients (8NIC/1NJC) were diagnosed. Patients with NIC had a median age of 16.5 (IQR 13-23) months at diagnosis, and two patients died during follow-up. Most of the patients started cysteamine therapy up to 5 months after diagnosis and reached CKD stages 3-4 within four years. During the follow-up, all but one of the NIC patients showed height for age Z-score values between -1.5 and -4.0. Two patients received kidney transplants, and one of them remains functional after 15 years. The single NJC was a 21-year-old female patient who received irregular cysteamine therapy and rapidly reached CKD stage 5. Genetic testing was positive in 7/7 cases, being del57kb the predominant variant (10/14 alleles).


Developing countries face many challenges in providing adequate healthcare. Our findings show clinical and diagnostic aspects to the medical and patient community that might contribute to the diagnostic approach and treatment access for cystinosis in Chile. Opportune genetic testing may facilitate early diagnosis that is known to be associated with a better prognosis.

DOI: 10.29245/2572-9411/2023/1.1208 View / Download Pdf

Carlos Ramírez-Paesano*, Camila Carrasco Chacón, Claudia Rodiera Clarens, Josep Rodiera Olive

Servei Central d’Anestesia (Anestalia), Centro Médico Teknon-Quironsalud, Barcelona.Spain

Angelman syndrome is the consequence of a genetic alteration in the chromosome 15 where the expression of the β3-subunits of GABA-A receptors is encoded. So, unpredictable responses to intravenous GABA-anesthetics may be the result.

We present a 19-year-old male patient with AS who required anesthesia to undergo an MRI and CT-scan. All his previous anesthetic procedures were complicated by severe emergence agitation with physical self-injury. His parents also mentioned that the patient reacted with paradoxical agitation due to benzodiazepines (midazolam) administration in previous anesthesia.

Dexmedetomidine (an α-2- adrenergic agonist) has been used in pediatric anesthesia as an adjuvant to attenuate agitation events after inhalation anesthesia. However, there are few publications on its use in patients with AS.

We describe the use of a single intravenous dose of dexmedetomidine (0.2μg/Kg) to prevent sevoflurane-related emergence agitation with good results.In addition, the potential benefits and precautions in using this non-GABA drug in patients with AS are discussed.

DOI: 10.29245/2572-9411/2022/3.1207 View / Download Pdf

Tran M. Nguyen1, Matt Downs 1, Neil Bennett2, Vitaliy Matyushenko3, Harumasa Nakamura4, Damjan Osredkar5, Shiwen Wu6, Nathalie Goemans7, Anna Ambrosini8, Rahsa El Sherifc9, Craig Campbell1*

1Department of Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada

2Action Duchenne, London, United Kingdom

3Children with Spinal Muscular Atrophy, Kharkiv, Ukraine

4Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan

5University Children's Hospital, Ljubljana, Slovenia

6Department of Neurology, the Third medical centre, Chinese PLA (People’s Liberation Army) General Hospital, Beijing, China

7University Hospitals Leuven, Leuven, Belgium

8Fondazione Telethon, Milano, Italy

9Myo-Care Neuromuscular Centre, Cairo, Egypt

Background: TREAT-NMD is a global neuromuscular (NM) organization, created to enhance infrastructure to facilitate novel therapeutics reaching patients. One main activity is aimed at supporting NM disease registries. These rare disease registries are useful to fill knowledge gaps for various stakeholders in the disease community using real world data. Although it is important to understand how patient data is being utilized in the TREAT-NMD network and other rare disease registries, there is no systematic process or consistent metric for documenting the academic output from these registries.

Objectives: The objective of this study was to determine the academic output from NM registries associated with the TREAT-NMD network, and the types of research the data is facilitating.

Results: A systematic search of EMBASE, Medline, Cochrane Central and SCOPUS was performed from inception to November 24, 2021. The search yielded a total of 650 results, with 231 full text studies assessed for eligibility and a total of 97 studies that met the inclusion criteria.

Conclusions: The results suggest publications from TREAT-NMD are mainly descriptive or methodologic. Rare disease registries, like the TREAT-NMD network, would benefit from clear and consistent metrics to facilitate reporting of academic output.

DOI: 10.29245/2572-9411/2022/2.1204 View / Download Pdf

Shahid Ullah1*, Alex Tonks2, Asif Ullah Khan1, Abdulsalam Muharrab Alruwaili3, Muhammad Arif lodhi1

1Abdul Wali khan University, Mardan, KPK, Pakistan

2Division of Cancer and Genetics, Cardiff University School of Medicine, UK

3Northern border university, Saudi Arabia

Case presentation

Prolidase enzyme plays a crucial role in proline-rich proteins metabolism and physiological processes such as inflammation, cell proliferation, wound healing, angiogenesis, and carcinogenesis. Due to mutations in the peptidase D (PEPD) gene, the catalytic activity of prolidase loss results in prolidase deficiency. Deficiency of prolidase enzyme is an autosomal inborn metabolic rare genetic disorder that has neither any proper treatment nor consensus for treatment. With approximately 100 cases recorded worldwide, the submitted manuscript describes the 2nd recorded case of prolidase deficiency, an extremely uncommon autosomal recessive disorder associated with collagen metabolism, in a 15-year-old Pakistan boy. The disorder typically becomes apparent during infancy. Affected individuals may have enlargement of the spleen (splenomegaly); in some cases, both the spleen and liver are enlarged (hepatosplenomegaly). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Here we present the report of a 15-year-old boy who has all the clinical manifestations of deficiency of prolidase. This is the 2nd case in Pakistan's 229,488,994 million population.

DOI: 10.29245/2572-9411/2022/2.1206 View / Download Pdf

Michelle T. Passos1, Patricia Varela2, Danilo E. Fernandes1, M. Goretti Polito1, João B. Pesquero2#, Gianna Mastroianni Kirsztajn1#*

1Division of Nephrology, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil

2Center for Research and Molecular Diagnostic of Genetic Diseases, Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil

#Both authors had equal participation in this study and share senior authorship

Introduction: Focal segmental glomerulosclerosis (FSGS) can be caused by mutations in the genes NPHS2, ACTN4, TRPC6, and INF2 among others, presenting variable levels of proteinuria, including nephrotic syndrome, that frequently progress to end-stage renal disease (ESRD). The establishment of the genotype-phenotype correlation caused by mutations in genes expressed in the podocyte could contribute to understanding their role in FSGS and to the decision-making in the clinical setting in similar cases.

Methods: Genomic DNA was extracted from peripheral blood of the proband, his brother, sister and mother. All the exons of the genes NPHS2, ACTN4, TRPC6, and INF2 were amplified by a polymerase chain reaction, purified, and sequenced by the Sanger method. The presence of variants was evaluated in the proband with FSGS and relatives, reviewed, and annotated using dbSNP and HGMD.

Results: In the clinical evaluation, the proband and his brother presented childhood-onset nephrotic syndrome, added with renal biopsies confirming FSGS, which was resistant to steroid and other immunosuppressive drugs, and progressed to ESRD. Both patients showed the variants p.P316S in NPHS2 and p.G894S in ACTN4, as well as the polymorphism p.R229Q in NPHS2, all variants in heterozygosis. Their parents were healthy, and the mother presented only the variant p.P316S in NPHS2 in heterozygosis.

Conclusions: The family members with FSGS had a combination of the variants p.P316S and p.R229Q in NPHS2, and p.G894S in ACTN4, shared similar clinical presentation, nephrotic syndrome with onset in late childhood that rapidly progressed to ESRD.

DOI: 10.29245/2572-9411/2022/1.1205 View / Download Pdf

Bhumika Dua, Rajaram Sharma*, Tapendra N. Tiwari, Saurabh Goyal

Department of Radio-Diagnosis, Pacific Institute of Medical Sciences, Umarda, Udaipur, Rajasthan, India

For the past few decades, a solid mass in the kidney with avid enhancement was considered renal cell carcinoma (RCC). With the advancement in radiological interventions, the understanding and treatment of a large number of tumours has changed. Oncocytomas are solid benign renal masses contributing 3-7% in all renal neoplasms. We report a case of a 32-year-old male who presented to our medicine OPD with abdominal pain and discomfort for about one month, later diagnosed with oncocytoma. We emphasize the importance of the typical imaging findings for the diagnosis and characterization of renal tumors.

DOI: https://doi.org/10.29245/2572-9411/2022/1.1203 View / Download Pdf

Moustapha Niasse1*, Awa Cheikh Ndao2, Ramadhane Bouchrane1, Siddiki Charifah1, Adama Bah1, 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

DOI: 10.29245/2572-9411/2021/2.1202 View / Download Pdf

Mona Al Mukaddam1, Kin Cheung2, Sammi Kile3, Michelle Davis3, Frederick S. Kaplan1,4 Robert J. Pignolo5*

1Departments of Medicine, Orthopaedic Surgery, and The Center for Research in FOP and Related Disorders, The Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA, USA

2BioSAS Consulting, Inc., Wellesley, Massachusetts, USA

3International FOP Association (IFOPA), North Kansas City, Missouri, USA

4Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine

5Chair, Geriatric Medicine & Gerontology, Robert and Arlene Kogod Professor of Geriatric Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA

Background:Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disease characterized by malformed great toes and progressive heterotopic ossification (HO) in soft tissues. Current standard-of-care is aimed at palliation of symptoms; there are no currently approved therapies to prevent HO. Recurrent episodes of HO starting in early life lead to cumulative disability, severe functional limitations, and shortened life span. Most individuals require assistive devices and extensive caregiver support before the second decade of life. Caregiver support is thought to be high, but the timing and extent of caregiver support in FOP has not been formally assessed. Methods: Using data from the International FOP Association (IFOPA) Global Registry on 299 patients (median age 21 years; range 0.1 to 78 years) from 54 countries, we characterized the extent of caregiver support by assessing the number of part-time and full-time caregivers and school aides reported by participants, based on age. Results: Over 50% of FOP Registry respondents reported a need for part-time or full-time home personal care attendants. The percentage of individuals who reported a requirement for bathing attendants and part- or full-time home personal care attendants increased with age (>1 part-time or full-time caregiver exceeded 30% for individuals >15 years of age), as did the number of part-time or full-time attendants. Support from school aides peaked between 9 and 15 years of age. Conclusion: Caregiver support in FOP is high in terms of time and amount of support needed, increases rapidly with age, and is substantial by the second decade of life. These findings highlight the urgent need for transformative treatments that will preserve the independence of individuals with FOP.

DOI: 10.29245/2572-9411/2021/1.1200 View / Download Pdf

Maria Goretti Polito1, Michelle Tiveron Passos1, Danilo Euclides Fernandes1, Gianna Mastroianni-Kirsztajn2*

1Department of Medicine (Nephrology), Federal University of São Paulo, São Paulo-SP, Brazil

2Associate Professor of Medicine, Department of Medicine (Nephrology), Federal University of São Paulo, São Paulo-SP, Brazil

Background: Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage kidney disease in children and adults. Although most cases are sporadic (s), familial (f) presentation is also described. The purpose of the present study was to establish clinical and laboratory profiles of fFSGS vs. primary sFSGS, contributing to the distinguishing diagnosis in clinical practice and best management, in particular when mutation analysis is not available.
Methods: Demographic, clinical and laboratorial parameters were studied in 124 patients 12 years and older with FSGS, subdivided in sFSGS (n=89) and fFSGS (n=35).
Results: General and clinical features were similar, as well as serum creatinine at disease presentation. Proteinuria levels were more frequently ≥ 3g/day in sFSGS (63.8%) than in fFSGS (44%, p=0.080), and serum albumin levels were < 3.0 g/dL in 45.8% and 20%, respectively (p=0.046). The groups were statistically different regarding steroid resistance, corresponding to 60% in sFSGS and 100% in fFSGS (p=0.001).
Conclusions: The studied groups were clinically similar, except that proteinuria tended to be higher (nephrotic range) and serum albumin was lower in sFSGS vs. fFSGS. In addition, all treated fFSGS patients were steroid resistant. At presentation it is important to characterize if the patient has fFSGS, that will contribute to further disease management, and disease history will be the first clue for such differential diagnosis.

DOI: 10.29245/2572-9411/2021/1.1199 View / Download Pdf

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.

DOI: 10.29245/2572-9411/2020/2.1197 View / Download Pdf

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

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

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

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

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

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

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

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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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

Ana Paula Vanz1, Têmis Maria Félix2,3, Neusa Sica da Rocha4, Ida Vanessa D. Schwartz2,5*

1Nurse department, Faculdades Integradas de Taquara, Taquara, Brazil

2Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

3Postgraduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

4Postgraduate Program in Medical Sciences: Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

5Department of Genetics, Universidade Federal do Rio Grande do Sul, Brazil

DOI: 10.29245/2572-9411/2019/3.1175 View / Download Pdf

Alberto Migliore1*, Gianfranco Gigliucci1, Sandro Tormenta2, Angelo De Cata3, Luca Gallelli4, Giovanni Iolascon5

1Rheumatology Unit and Research Center, S. Pietro Fatebenefratelli Hospital, Rome, Italy

2Radiology Unit, S. Pietro Fatebenefratelli Hospital, Rome, Italy

3Department of Medical Sciences, Division of Internal Medicine and Rheumatology Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (FG), Italy

4Chair of Pharmacology Department of Health Science, University of Catanzaro School of Medicine, and Operative Unit of Clinical Pharmacology and Pharmacovigilance, Azienda Ospedaliera MaterDomini, Catanzaro, Italy

5Department of Medical and Surgical Specialties and Dentistry, University of Campania "Luigi Vanvitelli", Naples, Italy

Hip osteoarthritis (OA) causes a set of symptoms that may lead to severe patient impairment, social isolation and morbidity, especially in the elderly. Eventually, patients become candidates for total hip replacement (THR); yet surgery may cause morbidity, increase costs and be too risky in some cases. Viscosupplementation (VS) by intra-articular hyaluronic acid (HA) injection has been shown to be effective to treat symptoms consequent to knee OA. VS is a viable option to treat hip OA too, provided that appropriate techniques are used to inject HA into the articular space. To this end, ultrasound-guided approaches have been developed that allow appropriate intra-articular injection eliminating the risk of exposure to ionizing radiation entailed by fluoroscopy. This review summarizes the results of clinical investigations concerning the use of a high molecular weight HA formulation, Hyalubrix/HyalOne, for treating hip OA symptoms. These results show that Hyalubrix/HyalOne has an enhanced safety profile, is effective from the first injection, significantly reduces NSAIDs consumption, and can be used for repeated therapy cycles over more years as a conservative therapy to delay THR. Nevertheless, it must be also considered that a significant placebo effect linked to intra-articular injections may exist, thus reducing the magnitude of HA benefits.

DOI: 10.29245/2572-9411/2019/2.1181 View / Download Pdf

Moustapha Niasse1*, Baïdy Sy Kane2, Kaba Condé3, Silly Touré4, Lamine Sarr5, Coumba Diouf1, 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 Stomatology and Maxillofacial surgery, University Hospital Aristide Le Dantec of Dakar, Senegal

5Department of Orthopaedics and Traumatology, University Hospital Aristide Le Dantec of Dakar, Senegal

Multiple exostosis disease is one of the hereditary diseases with autosomal dominant transmission. It is characterized by the proliferation of bone protuberances, especially located in the metaphysis of long bones.

Since 1993, advances have been noted in knowledge of the pathophysiology of this disease, in particular with the discovery of the mutation of EXT genes, found in 80% of multiple exostosis disease. These genes, tumor suppressors, code for proteins involved in the synthesis of heparan sulfates. The deficiency in quantity and quality of heparan sulfates leads to changes in certain metabolic processes, which leads to the development of ectopic growth plaques. This is responsible for the development of exostosis, but also for the low longitudinal growth of long bones. The disease phenotype may also associate abnormalities in the shape and length of long bones, such as the typical “Bessel Hagen” deformity. Clinically, bone masses are often painless. The rare complication (2 to 5% of cases) but the most feared is the transformation into chondrosarcoma, which motivates regular clinical and radiological monitoring of these patients. Treatment, mainly surgical, is indicated in case of symptoms (pain, increased exostosis volume after the end of growth, compression of neighboring organs.

DOI: 10.29245/2572-9411/2019/2.1182 View / Download Pdf

Ali M Agha1, Jeremy Burt2*

1The McGovern Medical School at UT Houston, Department of Internal Medicine, USA

2AdventHealth Orlando, Department of Radiology, USA

DOI: 10.29245/2572-9411/2019/2.1180 View / Download Pdf