Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression
Maria-Veronica Muñoz-RojasTaiane Alves VieiraRonaldo Campelo da CostaSimone Chaves FagondesÂngela Beatriz JohnLaura Bannach JardimLeonardo VedolinMarcia RaymundoPatricia DicksonEmil KakkisRoberto Giugliani
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Abstract In mucopolysaccharidosis I, deficiency of α‐ L ‐iduronidase can cause spinal cord compression (SCC) due to storage of glycosaminoglycans (GAGs) within the cervical meninges. As intravenous enzyme replacement therapy (ERT) is not likely to provide enzyme across the blood–brain barrier, standard treatment for this complication is usually surgical, which has a high morbidity and mortality risk. We report on the use of intrathecal (IT) laronidase in a MPS I patient with SCC who refused the surgical treatment. Assessments were performed at baseline, with clinical and biochemical evaluations, 4‐extremity somatosensory evoked potentials, 12 min walk test and MRI studies of the CNS. Changes on these parameters were evaluated after 4 IT infusions of laronidase administered monthly via lumbar puncture. To our knowledge, this was the first MPS patient who received IT ERT. No major adverse events were observed. There were no clinically significant changes in serum chemistries. CSF GAG results revealed pretreatment values slightly above normal standards: 13.3 mg/L (NV < 12 mg/L) which after IT laronidase infusions were within normal levels (10.3 mg/L). 12MWT presented a 14% improvement, with better performance on stability and gait control. Maximum voluntary ventilation showed 55.6% improvement considering the percentage of predicted (26.7% at baseline compared to 41.9%); Maximum Inspiration Pressure improved 36.6% of predicted (26.8% at baseline to 36.7%); Pulmonary diffusion improved 17.6% of predicted %. In conclusion, although the improvement observed in this case with IT laronidase should be confirmed in further patients, this procedure seems to be a safe treatment for SCC in MPS I. © 2008 Wiley‐Liss, Inc.Keywords:
Mucopolysaccharidosis I
Mucopolysaccharidosis
Spinal cord compression
Hurler syndrome
Somatosensory evoked potential
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.
Hurler syndrome
Mucopolysaccharidosis
Mucopolysaccharidosis I
Mucopolysaccharidosis type I
Lysosomal storage disease
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Mucopolysaccharidosis (MPS) type I is an autosomal recessive lysosomal storage disease caused by deficiency on the enzyme α-L-iduronidase. The spectrum of severity ranges from most severe Hurler syndrome, Hurler-Scheie syndrome to mildest form as Scheie syndrome. Enzyme replacement therapy (ERT) with recombinant α-L-iduronidase (laronidase) has shown to significantly improve the quality of life in children. Here we want to describe clinical characteristics, enzyme activity and genetic finding in the first patient with MPS type I who received aldurazyme replacement therapy in Marathwada, India.
Hurler syndrome
Mucopolysaccharidosis I
Mucopolysaccharidosis type I
Mucopolysaccharidosis
Lysosomal storage disease
Enzyme deficiency
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Mucopolysaccharidosis type I is an autosomal recessive disorder caused by deficiency of α-L-iduronidase and characterized by a progressive course with multisystem involvement. Clinically, Mucopolysaccharidosis type I is classified into two forms: severe (Hurler syndrome), which presents in infancy and is characterized by rapid progressive neurological involvement and attenuated (Hurler/Scheie and Scheie syndromes), which presents with slower progression and absent to mild nervous system involvement. The specific treatment for attenuated Mucopolysaccharidosis type I consists of enzyme-replacement therapy with laronidase (human recombinant α-L-iduronidase, Aldurazyme). We present here the clinical and laboratory results in an 12-year-old patient affected by the attenuated form of Mucopolysaccharidosis type I treated by enzyme-replacement therapy from the age of 5 months, compared with his 17 year old affected sister, who started therapy at 5 years of age. Clinical evaluation of these siblings shows that initiation of therapy prior of the onset of clinically detectable disease resulted in considerable improvement in outcome in the young sibling. After 12 years of enzyme-replacement therapy, facial appearance, linear growth rate, and liver and spleen volumes were normal; moreover, the degree of joint disease, vertebral, and cardiac valvular involvement were only minimal compared with those of his sister. This study demonstrates that early diagnosis and early initiation of enzyme-replacement therapy substantially modify the natural history of the attenuated form of Mucopolysaccharidosis type I.
Mucopolysaccharidosis
Mucopolysaccharidosis I
Hurler syndrome
Mucopolysaccharidosis type I
Lysosomal storage disease
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The mucopolysaccharidoses are a group of lysosomal storage diseases caused by deficiency of an enzyme required for the normal degradation of glycosaminoglycans. Patients with mucopolysaccharidosis typically have widespread lysosomal storage, skeletal and central nervous system disease, and hepatosplenomegaly. Some patients with mucopolysaccharidosis may benefit from enzyme replacement therapy or bone marrow transplantation. Animal models of mucopolysaccharidosis have proven valuable for the evaluation of the effectiveness of potential treatments for patients with lysosomal storage disease. A murine model of MPS VII (Sly syndrome) has proven particularly useful because of its well-defined genetics and its well-characterized clinical, pathologic, and biochemical alterations, which resemble those seen in patients with mucopolysaccharidosis. Correction of these alterations forms the basis for evaluation of the effectiveness of novel treatments. A wide range of therapies have been tested using this model, including enzyme replacement therapy, bone marrow, stem cell, and neural progenitor cell transplantation, and a variety of viral-mediated gene therapies. The inferences drawn from these therapeutic studies using the murine MPS VII model are likely generalizable to other lysosomal storage diseases.
Mucopolysaccharidosis
Mucopolysaccharidosis I
Lysosomal storage disease
Hurler syndrome
Hepatosplenomegaly
Mucopolysaccharidosis type I
Substrate reduction therapy
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Mucopolysaccharidosis I
Lysosomal storage disease
Mucopolysaccharidosis type I
Mucopolysaccharidosis
Hurler syndrome
Meninges
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Hurler syndrome
Mucopolysaccharidosis I
Mucopolysaccharidosis
Mucopolysaccharidosis type I
Hunter syndrome
Lysosomal storage disease
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Hurler syndrome
Mucopolysaccharidosis
Mucopolysaccharidosis type I
Mucopolysaccharidosis I
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Background: Laronidase (Aldurazyme®) is a recombinant formulation of α-L-iduronidase, the enzyme deficient in mucopolysaccharidosis type I (MPS-I); a disorder associated with skeletal dysplasia, restricted joint movement, short stature, obstructive pulmonary disease, cardiac valvular problems and cognitive impairment (in the severe and intermediate variants). Objective: To describe MPS-I and review data on the safety and efficacy of laronidase. Results: Laronidase is safe and effective in stabilizing or improving pulmonary function and physical endurance. As intravenously administered enzyme is unable to correct CNS disease, hematopoietic stem cell transplantation remains the primary treatment for Hurler's syndrome despite the morbidity and mortality risks. Conclusions: Palliative care remains part of the treatment. Long-term studies are required to ascertain the effect of enzyme therapy on survival and its effectiveness in modifying the disease course and reducing morbidity. Intrathecal administration is under investigation for patients with signs of cord compression secondary to glycosaminoglycan accumulation within the dura matter. The cost of therapy remains a concern.
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OBJECTIVES: Promote the early detection of the disease through pertinent clinical findings in patients with mucopolysaccharidosis. CASE REPORT: Patient with MPS I with typical clinical signs of the disease from a very early age were diagnosed only at 22 months old and will begin enzymatic replacement therapy. DISCUSSION: The disease, the earlier it is detected, the better and more effective the treatment, which may be enzyme replacement therapy, or, in the last case, transplantation of hematopoietic stem cells.
Hurler syndrome
Mucopolysaccharidosis
Mucopolysaccharidosis I
Lysosomal storage disease
Rare disease
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Mucopolysaccharidosis
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