18‐year follow‐up of enzyme‐replacement therapy in two siblings with attenuated mucopolysaccharidosis I

Abstract

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disorder caused by the deficiency of α‐L‐iduronidase and characterized by a progressive course with multisystem involvement. Clinically, MPS I is divided into two forms: (1) severe (Hurler syndrome), which presents in infancy and is characterized by rapid progressive neurological involvement; (2) attenuated (Hurler/Scheie and Scheie syndromes), which displays a slower progression and absent to mild nervous system involvement. The specific treatment for attenuated MPS I consists of enzyme‐replacement therapy with laronidase (human recombinant α‐L‐iduronidase, Aldurazyme). We present updated data after 18 years of laronidase treatment in two siblings affected by the attenuated form of MPS I who started therapy at 5 months and 5 years of age, respectively. Clinical and laboratory data of the siblings show that long‐term enzyme replacement therapy may improve/stabilize many symptoms already present at the time of the diagnosis and reduce the disease progression. This study confirms that early diagnosis and early initiation of enzyme‐replacement therapy are essential to modify positively the natural history of the attenuated form of MPS I.

Evaluation, in a highly specialised enzyme laboratory, of a digital microfluidics platform for rapid assessment of lysosomal enzyme activity in dried blood spots

“…4 Treatments are available for many LSDs, including enzyme replacement therapy (ERT), haematopoietic stem cell transplantation, substrate reduction therapy, chaperone therapy, and gene therapy. 5 With therapies available and evidence showing that earlier treatment leads to more favourable outcomes for affected patients, [6][7][8] there is a growing interest in detecting patients with LSDs as soon as possible. [9][10][11][12] A crucial part in the diagnosis of LSDs is the measurement of lysosomal enzyme activity from leucocytes, plasma, or dried blood spots (DBS).…”

Light and Shadows in Newborn Screening for Lysosomal Storage Disorders: Eight Years of Experience in Northeast Italy

“…Enzyme analyses on leukocytes/lymphocytes, biochemical assays demonstrating accumulation and gene analyses can confirm the clinical diagnosis [ 5 , 6 ]. The treatment (enzyme-replacement therapy ERT, hematopoietic stem-cell transplantation HSCT, chaperones and gene therapy) can significantly improve outcomes, but the progressive nature of these diseases makes early diagnosis essential [ 7 , 8 , 9 , 10 ].…”