ABSTRACT
Introduction: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by TPP1 gene variants, with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible in an attempt to improve quality of life and survival. This study describes the clinical characteristics as well as the response to treatment with cerliponase alfa. Materials and methods: A retrospective study was conducted in five Latin-American countries, using clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed. Results: A total of 36 patients were observed (range of follow-up of 61-110 weeks post-treatment). At presentation, patients with the classic phenotype (n = 16) exhibited regression in language (90%), while seizures were the predominant symptom (87%) in patients with the atypical phenotype (n = 20). Median age of symptom onset and time to first specialized consultation was 3 (classical) and 7 (atypical) years, while the median time interval between onset of symptoms and treatment initiation was 4 years (classical) and 7.5 (atypical). The most frequent variant was c.827 A > T in 17/72 alleles, followed by c.622C > T in 6/72 alleles. All patients were treated with cerliponase alfa, and either remained functionally stable or had a loss of 1 point on the CLN2 scale, or up to 2 points on the Wells Cornel and Hamburg scales, when compared to pretreatment values. Discussion and conclusion: This study reports the largest number of patients with CLN2 currently on treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotypes and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower progression or stabilization of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes.
ABSTRACT
PURPOSE: This study aims to raise awareness of the need for research and appropriate guidelines for managing spinal cord issues in adult patients with mucopolysaccharidosis (MPS) and transition of these patients from pediatric to adult care. METHODS: Pediatric/adult neurosurgeons, orthopedic spine surgeons, and treating physicians with expertise in metabolic disorders and spinal cord issues were invited to complete a survey to assess their experience with spinal cord problems in MPS and their opinion on transitioning routes from pediatric to adult care. RESULTS: Twenty specialists completed the survey; 16 had treated spinal cord issues in patients with MPS. Foramen magnum and cervical stenosis (87%), atlanto-axial instability (67%), and lumbar spine instability (33%) were the main spinal cord issues encountered; 28% had treated adult patients for one or more spinal cord issues. In 40% of cases, this concerned an intervention or procedures performed during childhood. The main specialist responsible for the care of adult patients with MPS differed considerably between institutions and included both pediatric and adult specialists (30% pediatric neurosurgeons, 10% pediatric spine orthopedic surgeons, 30% adult spine neurosurgeons, 20% general adult surgeons). The preferred option (> 50%) for the transition of care was an interdisciplinary team of pediatric and adult specialists. CONCLUSIONS: Further work needs to be done to address problems of managing spinal cord issues in adult patients with MPS. Currently, the responsibility for the care of patients with MPS with spinal cord issues is inconsistent. The best strategy for transitioning these patients from pediatric to adult care is likely an interdisciplinary approach.
