RT Generic
T1 Collaborative model for diagnosis and treatment of very rare diseases: experience in Spain with thymidine kinase 2 deficiency.
A1 Dominguez-Gonzalez, Cristina
A1 Madruga-Garrido, Marcos
A1 Hirano, Michio
A1 Marti, Itxaso
A1 Martin, Miguel A
A1 Munell, Francina
A1 Nascimento, Andres
A1 Olive, Montse
A1 Quan, Joanne
A1 Sardina, M Dolores
A1 Marti, Ramon
A1 Paradas, Carmen
K1 Mitochondrial disease
K1 Mitochondrial medicine
K1 Thymidine kinase 2 deficiency (TK2d)
AB Mitochondrial diseases are difficult to diagnose and treat. Recent advances in genetic diagnostics and more effective treatment options can improve patient diagnosis and prognosis, but patients with mitochondrial disease typically experience delays in diagnosis and treatment. Here, we describe a unique collaborative practice model among physicians and scientists in Spain focused on identifying TK2 deficiency (TK2d), an ultra-rare mitochondrial DNA depletion and deletions syndrome. This collaboration spans research and clinical care, including laboratory scientists, adult and pediatric neuromuscular clinicians, geneticists, and pathologists, and has resulted in diagnosis and consolidation of care for patients with TK2d. The incidence of TK2d is not known; however, the first clinical cases of TK2d were reported in 2001, and only ~ 107 unique cases had been reported as of 2018. This unique collaboration in Spain has led to the diagnosis of more than 30 patients with genetically confirmed TK2d across different regions of the country. Research affiliate centers have led investigative treatment with nucleosides based on understanding of TK2d clinical manifestations and disease mechanisms, which resulted in successful treatment of a TK2d mouse model with nucleotide therapy in 2010. Only 1 year later, this collaboration enabled rapid adoption of treatment with pyrimidine nucleotides (and later, nucleosides) under compassionate use. Success in TK2d diagnosis and treatment in Spain is attributable to two important factors: Spain's fully public national healthcare system, and the designation in 2015 of major National Reference Centers for Neuromuscular Disorders (CSURs). CSUR networking and dissemination facilitated development of a collaborative care network for TK2d disease, wherein participants share information and protocols to request approval from the Ministry of Health to initiate nucleoside therapy. Data have recently been collected in a retrospective study conducted under a Good Clinical Practice-compliant protocol to support development of a new therapeutic approach for TK2d, a progressive disease with no approved therapies. The Spanish experience in diagnosis and treatment of TK2d is a model for the diagnosis and development of new treatments for very rare diseases within an existing healthcare system.
PB BioMed Central Ltd.
YR 2021
FD 2021-10-02
LK https://hdl.handle.net/10668/27812
UL https://hdl.handle.net/10668/27812
LA en
NO Domínguez-González C, Madruga-Garrido M, Hirano M, Martí I, Martín MA, Munell F, et al. Collaborative model for diagnosis and treatment of very rare diseases: experience in Spain with thymidine kinase 2 deficiency. Orphanet J Rare Dis. 2021 Oct 2;16(1):1-9.
DS RISalud
RD Apr 19, 2025