Vol 7-2 Research Article

Academic Productivity from Rare Neuromuscular Disease Registries: A Systematic Review

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
Vol 7-2 Case Report

A Case report of rare disease Prolidase deficiency in a 15-year-old Pakistan boy

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
Vol 7-1 Case Report

Effect of combined NPHS2 and ACTN4 variants in the onset and severity of focal segmental glomerulosclerosis

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
Vol 7-1 Short Review Article

Typical Imaging Findings of Renal Oncocytoma

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
Vol 6-2 Case Report

Ankylosing Spondylitis associated with Adult Still's Disease: The First Senegalese Case Report

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
Vol 6-1 Short Communication

Caregiver Support in Fibrodysplasia Ossificans Progressiva

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
Vol 6-1 Research Article

Clinical and laboratory features that differentiate familial from sporadic focal segmental glomerulosclerosis in adolescents and adults

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