Response of the ENPP1 ‐Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Intracerebroventricular enzyme replacement therapy (ICV-ERT) for CLN2 disease represents the first approved treatment for neuronal ceroid lipofuscinosis (NCL) diseases. It is the first treatment where a recombinant lysosomal enzyme, cerliponase alfa, is administered into the lateral cerebral ventricles to reach the central nervous system, the organ affected in CLN2 disease. If untreated, CLN2 children show first symptoms such as epilepsy and language developmental delay at 2-4 years followed by rapid loss of motor and language function, vision loss, and early death. Treatment with cerliponase alfa has shown to slow the rapid neurologic decline. However, the mode of administration by 4 hour-long intracerebroventricular infusions every 14 days represents a potentially greater risk of infection compared to intravenous enzyme replacement therapies. The Hamburg NCL Specialty Clinic was the first site worldwide to perform intracerebroventricular enzyme replacement therapy in children with CLN2 disease. In order to ensure maximum patient safety, we analysed data from our center from more than 3000 intracerebroventricular enzyme replacement therapies in 48 patients over 6 years with regard to the occurrence of device-related adverse events and device infections. Since starting intracerebroventricular enzyme replacement therapy, we have also developed and continuously improved the “Hamburg Best Practice Guidelines for ICV–Enzyme Replacement Therapy (ERT) in CLN2 Disease.” Results from this study showed low rates for device-related adverse events and infections with 0.27% and 0.33%, respectively. Therefore, following our internal procedural guidelines has shown to improve standardization and patient safety of intracerebroventricular enzyme replacement therapy for CLN2 disease.

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Description of a patient with infantile onset Pompe disease after 45 months of enzyme replacement therapy

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2017.12.339 ◽

2018 ◽

Vol 123 (2) ◽

pp. S124-S125

Author(s):

Roberto Sandobal Pacheco ◽

Diana Espinosa Villanueva ◽

Adriana Alcnatara Salinas ◽

Jorge A. Romero Ramirez ◽

Jose Antonio Vasquez Galeana ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Enzyme Replacement

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One-year results of olipudase alfa enzyme replacement therapy in children with chronic visceral and neurovisceral acid sphingomyelinase deficiency

Molecular Genetics and Metabolism ◽

10.1016/s1096-7192(21)00260-2 ◽

2021 ◽

Vol 132 ◽

pp. S115

Author(s):

George Diaz ◽

Roberto Giugliani ◽

Nathalie Guffon ◽

Simon Jones ◽

Eugen Mengel ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Acid Sphingomyelinase ◽

Enzyme Replacement ◽

Sphingomyelinase Deficiency ◽

One Year

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Morquio A syndrome and effect of enzyme replacement therapy in different age groups of Turkish patients: a case series

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-01761-0 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Sebile Kılavuz ◽

Sibel Basaran ◽

Deniz Kor ◽

Fatma Derya Bulut ◽

Sevcan Erdem ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Clinical Data ◽

Treatment Initiation ◽

Case Series ◽

Enzyme Replacement ◽

Morquio A ◽

Over Time ◽

Morquio A Syndrome

Abstract Background This case series includes longitudinal clinical data of ten patients with Morquio A syndrome from south and southeastern parts of Turkey, which were retrospectively collected from medical records. All patients received enzyme replacement therapy (ERT). Clinical data collected included physical appearance, anthropometric data, neurological and psychological examinations, cardiovascular evaluation, pulmonary function tests, eye and ear-nose-throat examinations, endurance in the 6-min walk test and/or 3-min stair climb test, joint range of motion, and skeletal investigations (X-rays, bone mineral density). Results At the time of ERT initiation, two patients were infants (1.8 and 2.1 years), five were children (3.4–7.1 years), and three were adults (16.5–39.5 years). Patients had up to 4 years follow-up. Most patients had classical Morquio A, based on genotypic and phenotypic data. Endurance was considerably reduced in all patients, but remained relatively stable or increased over time in most cases after treatment initiation. Length/height fell below normal growth curves, except in the two infants who started ERT at ≤ 2.1 years of age. All patients had skeletal and/or joint abnormalities when ERT was started. Follow-up data did not suggest improvements in skeletal abnormalities, except in one of the younger infants. Nine patients had corneal clouding, which resolved after treatment initiation in the two infants, but not in the other patients. Hepatomegaly was reported in seven patients and resolved with treatment in five of them. Other frequent findings at treatment initiation were coarse facial features (N = 9), hearing loss (N = 6), and cardiac abnormalities (N = 6). Cardiac disease deteriorated over time in three patients, but did not progress in the others. Conclusions Overall, this case series with Morquio A patients confirms clinical trial data showing long-term stabilization of endurance after treatment initiation across ages and suggest that very early initiation of ERT optimizes growth outcomes.

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