Article
Medicine, General & Internal
Derralynn A. Hughes, Patrick Deegan, Pilar Giraldo, Ozlem Goker-Alpan, Heather Lau, Elena Lukina, Shoshana Revel-Vilk, Maurizio Scarpa, Jaco Botha, Noga Gadir, Ari Zimran
Summary: This study used data from the Gaucher Outcome Survey (GOS) to investigate the reasons for and consequences of switching between enzyme replacement therapies (ERT) and substrate reduction therapies (SRT) in patients with type 1 Gaucher disease (GD1). The study found that the most common reasons for switching were duration of infusion, drug shortage, and adverse events. The bodyweight and hematologic parameters of the patients remained relatively stable before and after switching.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Weijing Kong, Cheng Lu, Yingxue Ding, Yan Meng
Summary: This paper provides an update on approved therapies and potential curative therapies for Gaucher disease (GD), the most common lysosomal disorder.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Paulina Szymanska-Rozek, Barbara Czartoryska, Grazina Kleinotiene, Patryk Lipinski, Anna Tylki-Szymanska, Agnieszka Lugowska
Summary: Chitotriosidase is an enzyme produced by activated macrophages, especially in Gaucher disease, where macrophages loaded with phagocytozed glycosphingolipid secrete chitotriosidase in proportion to the degree of overload. Gaucher disease is caused by the deficiency of beta-glucocerebrosidase activity and results in the storage of glucosylceramide in tissue macrophages. Chitotriosidase has been found to be a sensitive biomarker for enzyme replacement therapy in GD patients.
Article
Biochemistry & Molecular Biology
Pawel Dubiela, Paulina Szymanska-Rozek, Andrzej Eljaszewicz, Patryk Lipinski, Piotr Hasinski, Dorota Giersz, Alicja Walewska, Marlena Tynecka, Marcin Moniuszko, Anna Tylki-Szymanska
Summary: Gaucher disease, caused by GBA1 gene variants, is characterized by hepatosplenomegaly, hematological abnormalities, and bone disease. GBA1 variants are also important risk factors for Parkinson's disease. A study investigated biomarkers for Gaucher disease and Parkinson's disease in patients receiving enzyme replacement therapy (ERT). The results showed elevated levels of alpha-synuclein mRNA in GD3 patients and L444P carriers, while GD1 patients, GBA1 carriers with unknown variants, and healthy controls had low levels of alpha-synuclein mRNA. The level of alpha-synuclein mRNA did not correlate with age in GD patients treated with ERT, except for L444P carriers.
Article
Medicine, General & Internal
Xia Zhan, Huiwen Zhang, Gustavo H. B. Maegawa, Yu Wang, Xiaolan Gao, Dengbin Wang, Jinning Li
Summary: The study aimed to evaluate the hematologic and visceral outcomes, biomarker changes, and safety of ambroxol therapy for patients with Gaucher disease without disease-specific treatment. The results showed that long-term treatment with ambroxol was safe and associated with patient improvement, especially in patients with relatively mild symptoms and those who received initial treatment at younger ages.
Article
Genetics & Heredity
Wen-Li Lu, Yin-Hsiu Chien, Fuu-Jen Tsai, Wuh-Liang Hwu, Yen-Yin Chou, Shao-Yin Chu, Meng-Ju Li, An-Ju Lee, Chao-Chuan Liao, Chung-Hsing Wang, Ni-Chung Lee
Summary: This study investigated the clinical features of patients diagnosed with Gaucher disease (GD) during different eras in Taiwan. The results showed a higher proportion of GD3 individuals in Taiwan compared to worldwide reports. The major subtypes identified through newborn screening (NBS) were GD2 and GD3. Early diagnosis and enzyme replacement therapy (ERT) were effective in improving hematological manifestations and preventing skeletal complications, but there is still a need for effective intervention for neurological dysfunction.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Article
Genetics & Heredity
Patrick Deegan, Aneal Khan, Jose Simon Camelo, Julie L. Batista, Neal Weinreb
Summary: The GRAF score is a tool that, when combined with bone density and other modifiable, non-GD-specific risk factors (such as smoking, alcohol intake, frailty), informs physicians and previously untreated GD1 patients about the risk of future fractures after starting imiglucerase, regardless of potential switch to alternative ERT or substrate reduction therapy. The GRAF score can also help predict the extent to which fracture risk increases with further delay in treatment initiation.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Tama Dinur, Peter Bauer, Christian Beetz, Claudia Cozma, Michal Becker-Cohen, Majdolen Istaiti, Arndt Rolfs, Volha Skrahina, Ari Zimran, Shoshana Revel-Vilk
Summary: Glucosylsphingosine (lyso-Gb1), the deacylated form of glucocerebroside, is a specific and sensitive biomarker for diagnosing Gaucher disease (GD). This study assessed the impact of lyso-Gb1 levels at the time of diagnosis on treatment decisions in newly diagnosed GD patients. The findings suggest that higher lyso-Gb1 levels are associated with the initiation of GD-specific therapy, especially among mildly affected patients. However, the exact cutoff value may vary due to differences in measurement methodologies and units between laboratories.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pediatrics
Gianluca Bossu, Laura Pedretti, Lorenzo Bertolini, Susanna Esposito
Summary: Gaucher Disease (GD) is an autosomal recessive disorder characterized by a deficiency of the lysosomal enzyme beta-glucocerebrosidase, leading to the accumulation of lipids in tissues. The diagnosis of GD is confirmed through enzyme activity measurement and genetic testing. In this case study, a young girl with splenomegaly and hepatic gaucheroma was diagnosed with GD through genetic analysis, highlighting the importance of early detection and treatment to prevent complications.
Article
Genetics & Heredity
Simona D'Amore, Kathleen Page, Aimee Donald, Khadijeh Taiyari, Brian Tom, Patrick Deegan, Chong Y. Tan, Kenneth Poole, Simon A. Jones, Atul Mehta, Derralynn Hughes, Reena Sharma, Robin H. Lachmann, Anupam Chakrapani, Tarekegn Geberhiwot, Saikat Santra, Siddarth Banka, Timothy M. Cox
Summary: The Gaucher Investigative Therapy Evaluation study collected comprehensive data on 250 patients with Gaucher disease in the UK to analyze the disease course, revealing a high prevalence of skeletal manifestations and unexpected neurological features. The study stratified the disease with respect to advanced therapies, showing that splenectomy was associated with increased risk of fragility fractures and orthopedic surgery, highlighting the complex interplay of systemic, skeletal, and neurological manifestations in Gaucher disease.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Tama Dinur, Ulrike Grittner, Shoshana Revel-Vilk, Michal Becker-Cohen, Majdolen Istaiti, Claudia Cozma, Arndt Rolfs, Ari Zimran
Summary: Enzyme replacement therapy (ERT) and substrate reduction therapy have been standard treatments for type 1 Gaucher disease for thirty years. This study compared the impact of three different ERTs on GD1 patients, with velaglucerase alfa showing a faster decrease in lyso-Gb1 levels. Significant variations in lyso-Gb1 levels were observed among different patients and within the same patient across all ERTs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medical Laboratory Technology
Ramazan Uzen, Fahri Bayram, Huseyin Dursun, Fatih Kardas, Pinar Altin-Celik, Mustafa Cakir, Ahmet Eken, Nurhan Cucer, Hamiyet Donmez-Altuntas
Summary: This study evaluated plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters in patients with Gaucher disease (GD) and carriers. The results showed that CBMN-cyt assay parameters were not significantly different between patients with GD and carriers compared to controls, but plasma 8-OHdG levels were higher in both patients with GD and carriers.
CLINICAL BIOCHEMISTRY
(2023)
Article
Genetics & Heredity
Menno ter Huurne, Benjamin L. Parker, Ning Qing Liu, Elizabeth Ling Qian, Celine Vivien, Kathy Karavendzas, Richard J. Mills, Jennifer T. Saville, Dad Abu-Bonsrah, Andrea F. Wise, James E. Hudson, Andrew S. Talbot, Patrick F. Finn, Paolo G. V. Martini, Maria Fuller, Sharon D. Ricardo, Kevin I. Watt, Kathy M. Nicholls, Enzo R. Porrello, David A. Elliott
Summary: This study evaluated the efficacy of nucleoside-modified messenger RNA (modRNA) treatment for Fabry disease and validated it using a human cardiac model generated from induced pluripotent stem cells. The results showed that modRNA treatment restored α-Galactosidase A enzyme activity and reduced glycosphingolipid accumulation, demonstrating its therapeutic potential.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Endocrinology & Metabolism
Neal J. Weinreb, Jose Simon Camelo, Joel Charrow, Monica R. McClain, Pramod Mistry, Nadia Belmatoug
Summary: The study observed the long-term effects of enzyme replacement therapy on Gaucher disease patients and found that improvements were sustained over 20 years, with some symptoms showing improvement. Patients who started treatment in childhood achieved normal weight and height in adulthood.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Hematology
Barry E. Rosenbloom, Maria Domenica Cappellini, Neal J. Weinreb, Marta Dragosky, Shoshana Revel-Vilk, Julie L. Batista, Davorka Sekulic, Pramod K. Mistry
Summary: This study evaluated the incidence of hematological malignancies, gammopathies, and solid tumors in GD1 patients and found that GD1 patients have a higher risk of hematological malignancies, particularly non-Hodgkin lymphoma and multiple myeloma. Furthermore, GD1 patients were found to have an increased risk of solid malignancies of the liver, kidney, melanoma, and breast, but a lower risk of colorectal, prostate, and lung cancer.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Genetics & Heredity
Patricia Ioschpe Gus, Karina Carvalho Donis, Diane Marinho, Tiago Franco Martins, Carolina Fischinger Moura de Souza, Rafael Barboza Carloto, Gabriel Leivas, Ida Vanessa Doederlein Schwartz
Summary: Eye abnormalities are common in late-diagnosed HCU patients, with ectopia lentis and myopia being the most frequent findings. Regular ophthalmological evaluations are important for these patients.
OPHTHALMIC GENETICS
(2021)
Article
Genetics & Heredity
Suelen Porto Basgalupp, Karina Carvalho Donis, Marina Siebert, Filippo Pinto e Vairo, Osvaldo Artigalas, Louise L. de Camargo Pinto, Sidney Behringer, Ute Spiekerkoetter, Luciana Hannibal, Ida Vanessa D. Schwartz
Summary: Gaucher disease is classified into types I, II, and III based on neurological complications, with type II being the most severe. Abnormalities in B-12 metabolism markers have been observed in type I patients, but a 2-month-old male with type II presented with elevated B-12 and holo-TC levels. This study suggests that higher levels of holo-TC may be associated with a more severe form of Gaucher disease and serve as a biomarker for type II.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Biochemistry & Molecular Biology
Gerda Cristal Villalba Silva, Taciane Borsatto, Ida Vanessa Doederlein Schwartz, Fernanda Sperb-Ludwig
Summary: Reduced biotinidase activity is associated with genotype-phenotype discrepancies, but variations in the 3'UTR region do not explain these differences. MiRNAs and regulatory elements may play a significant role in the genotype-phenotype association.
GENETICS AND MOLECULAR BIOLOGY
(2022)
Article
Medicine, General & Internal
Matheus V. M. B. Wilke, Bibiana M. Oliveira, Alessandra Pereira, Maria Juliana R. Doriqui, Fernando Kok, Carolina F. M. Souza
Summary: This study reports two unrelated cases of children with CSNK2B variants, each presenting with a different disease. Case 1 is a 7-month-old Caucasian female with severe hypotonia and drug-refractory myoclonic epilepsy, harboring a likely pathogenic de novo variant. Case 2 is a 5-year-old Latino male with craniodigital intellectual disability syndrome, carrying a likely pathogenic de novo variant. Both cases had distinct dysmorphic features.
JOURNAL OF MEDICAL CASE REPORTS
(2022)
Article
Genetics & Heredity
Marta Zawadzka, Magdalena Krygier, Malgorzata Pawlowicz, Matheus Vernet Machado Bressan Wilke, Karolina Rutkowska, Naig Gueguen, Valerie Desquiret-Dumas, Eric W. Klee, Lisa A. Schimmenti, Jaroslaw Slawek, Vincent Procaccio, Rafal Ploski, Maria Mazurkiewicz-Beldzinska
Summary: Leigh syndrome is a progressive neurodegenerative disease with extensive clinical and biochemical features. This study describes three Polish patients and provides further evidence for the association of DNAJC30 gene variants with Leigh syndrome. DNAJC30-associated Leigh syndrome exhibits clinical heterogeneity with variable age at onset, movement disorder phenotype, and blood lactate level.
Review
Genetics & Heredity
A. L. S. Pessoa, A. M. Martins, E. M. Ribeiro, N. Specola, A. Chiesa, D. Vilela, E. Jurecki, D. Mesojedovas, I. V. D. Schwartz
Summary: This is a systematic literature review investigating the impact of phenylketonuria (PKU) on affected individuals and healthcare resources in Latin American countries. The results demonstrate a high clinical burden in PKU patients in Latin American countries, with intellectual disability, motor delay, and speech deficit being common complications.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Nutrition & Dietetics
Bruna B. dos Santos, Karina Colonetti, Tatiele Nalin, Bibiana M. de Oliveira, Carolina F. M. de Souza, Poli Mara Spritzer, Ida V.d. Schwartz
Summary: This study evaluated the body composition of patients with hepatic glycogen storage disorders (GSDs) and found a high frequency of increased fat mass. The study also suggested that treatment with uncooked cornstarch (UCCS) is associated with excess weight and may impair protein intake, leading to a decrease in lean mass.
Article
Biochemistry & Molecular Biology
Matheus Vernet Machado Bressan Wilke, Bibiana Mello de Oliveira, Rodrigo Tzovenos Starosta, Marwan Shinawi, Liang Lu, Mai He, Yamin Ma, Janis Stoll, Carolina Fischinger Moura de Souza, Ana Cecilia Menezes de Siqueira, Sandra Maria Goncalves Vieira, Carlos Thadeu Cerski, Lilia Farret Refosco, Ida Vanessa Doederlein Schwartz
Summary: This study describes five cases of patients with GSD IV, with different ages of onset and outcomes, and identifies a novel GBE1 variant. The research findings indicate that GSD IV has different ages of onset and diverse cardiac phenotypes, and is associated with high levels of chitotriosidase. Dietary intervention did not show clear improvement in these cases.
Article
Neurosciences
Ida Vanessa Doederlein Schwartz, Andrea Amaro Quesada, Erlane Marques Ribeiro, Ana Maria Martins, Daniel Reda Fenga Vilela, Andre Pessoa
Summary: The National Neonatal Screening Program in Brazil allows early treatment for patients with PKU, preventing severe neurological damage and mental disabilities. However, a significant percentage of early-treated patients with PKU still experience cognitive deficits. This study recommends nine tools that can be used to assess quality of life and neuropsychological outcomes in PKU patients in Brazil.
ARQUIVOS DE NEURO-PSIQUIATRIA
(2023)
Article
Endocrinology & Metabolism
Yilmaz Yildiz, Oya Kuseyri Huebschmann, Ayca Akgoz Karaosmanoglu, Filippo Manti, Meryem Karaca, Ida Vanessa D. Schwartz, Roser Pons, Eduardo Lopez-Laso, Natalia Alexandra Julia Palacios, Francesco Porta, Ivana Kavecan, Mehmet Cihan Balci, Marisela E. E. Dy-Hollins, Suet-Na Wong, Mari Oppeboen, Leonardo Simao Medeiros, Leila Cristina Pedroso de Paula, Angeles Garcia-Cazorla, Georg F. F. Hoffmann, Kathrin Jeltsch, Vincenzo Leuzzi, Gulden Gokcay, Daniel Huebschmann, Inga Harting, Z. Alev Ozon, Serap Sivri, Thomas Opladen
Summary: This study provides standardized results on levodopa-refractory hyperprolactinemia and pituitary magnetic resonance imaging abnormalities in patients with inherited disorders of biogenic amine metabolism. The most common diagnosis was tetrahydrobiopterin deficiency (n = 22). Symptoms related to hyperprolactinemia, such as menstruation-related abnormalities, pubertal delay or arrest, galactorrhea, and decreased sexual functions, were observed in some individuals. Treatment with the dopamine agonist cabergoline was effective in relieving hyperprolactinemia-related symptoms.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Genetics & Heredity
Matheus Vernet Machado Bressan Wilke, Fabiano Poswar, Wyllians Vendramini Borelli, Kristiane Michelin Tirelli, Devora Natalia Randon, Franciele Fatima Lopes, Fernanda Bender Pasetto, Fernanda Medeiros Sebastiao, Gabrielle Dineck Iop, Larissa Faqueti, Layzon Antonio da Silva, Francyne Kubaski, Artur Francisco Schumacher Schuh, Roberto Giugliani, Ida Vanessa Doederlein Schwartz
Summary: This study assessed the prevalence and evolution of non-motor symptoms (NMS) compatible with Parkinson's disease (PD) in a cohort of Gaucher disease (GD) patients in South Brazil. The results showed that the patient with the highest number of NMS developed PD four years later, highlighting the importance of longitudinal follow-up. CSF and plasma analysis may provide insights into the neurodegenerative processes linking PD and the lysosomal environment. Further analysis is needed to understand this relationship.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Letter
Multidisciplinary Sciences
Fernanda Staniscuaski, Eugenia Zandona, Fernanda Reichert, Rossana C. Soletti, Pamela B. Mello-Carpes, Giulia A. Wiggers, Ida V. D. Schwartz, Fernanda P. Werneck, Zelia M. c Ludwig, Adriana Neumann, Camila Infanger Almeida, Leticia De Oliveira
ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS
(2023)
Article
Biochemistry & Molecular Biology
Fernanda Sperb-Ludwig, Nataniel Floriano Ludwig, Gustavo Mottin Rizowy, Renata Voltolini Velho, Ida Vanessa Doederlein Schwartz
Summary: Mucolipidosis II and III are genetic diseases caused by pathogenic variants in GNPTAB and GNPTG genes. This study suggests that substrate reduction therapy and immunomodulation may be beneficial in reducing substrate accumulation and improving the phenotype of patients.
GENETICS AND MOLECULAR BIOLOGY
(2023)
Article
Rheumatology
Matheus V. M. B. Wilke, Eva Morava-Kozicz, Matthew J. Koster, Christopher T. Schmitz, Shannon Kaye Foster, Mrinal Patnaik, Kenneth J. Warrington, Eric W. Klee, Filippo Pinto E. Vairo
Summary: This case demonstrates the diagnostic challenge posed by high variant allele frequency detected through exome sequencing for VEXAS syndrome. Sequencing different tissue samples was necessary to confirm the mosaic state of the variant.
