Papers by Rossella Parini
—Background: Pompe disease is a progressive metabolic neuromuscular disorder resulting from defic... more —Background: Pompe disease is a progressive metabolic neuromuscular disorder resulting from deficiency of lysosomal acid-glucosidase (GAA). Infantile-onset Pompe disease is characterized by cardiomyopathy, respiratory and skeletal muscle weakness, and early death. The safety and efficacy of recombinant human (rh) GAA were evaluated in 18 patients with rapidly progressing infantile-onset Pompe disease. Methods: Patients were diagnosed at 6 months of age and younger and exhibited severe GAA deficiency and cardiomyopathy. Patients received IV infusions of rhGAA at 20 mg/kg (n 9) or 40 mg/kg (n 9) every other week. Analyses were performed 52 weeks after the last patient was randomized to treatment. Results: All patients (100%) survived to 18 months of age. A Cox proportional hazards analysis demonstrated that treatment reduced the risk of death by 99%, reduced the risk of death or invasive ventilation by 92%, and reduced the risk of death or any type of ventilation by 88%, as compared to an untreated historical control group. There was no clear advantage of the 40-mg/kg dose with regard to efficacy. Eleven of the 18 patients experienced 164 infusion-associated reactions; all were mild or moderate in intensity. Conclusions: Recombinant human acid-glucosidase is safe and effective for treatment of infantile-onset Pompe disease. Eleven patients experienced adverse events related to treatment, but none discontinued. The young age at which these patients initiated therapy may have contributed to their improved response compared to previous trials with recombinant human acid-glucosidase in which patients were older.
Glycogenosis type III (GSD III) is an autosomal recessive disorder due to amylo-1,6-glucosidase d... more Glycogenosis type III (GSD III) is an autosomal recessive disorder due to amylo-1,6-glucosidase deficiency. This disease causes limit dextrin storage in affected tissues: liver, skeletal muscles, and heart in GSD IIIa and only liver in GSD IIIb. Cardiomyopathy is quite frequent in GSD IIIa with variable severity and progression of manifestations.
a r t i c l e i n f o Available online xxxx Keywords: MPS II Hunter disease Hunter syndrome Mucop... more a r t i c l e i n f o Available online xxxx Keywords: MPS II Hunter disease Hunter syndrome Mucopolysaccharidosis type II ERT Enzymatic replacement therapy Idursulfase Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosami-noglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood–brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m 2 decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood–brain barrier, might in the future improve the MPS II outcome. j o u r n a l h o m e p a g e : h t t p : / / w w w. j o u r n a l s. e l s e v i e r. c o m / m o l e c u l a r-g e n e t i c s-a n d-m e t a b o l i s m-r e p o r t s /
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/authorsrights
Objectives: The original manufacturers recommended dose of enzyme replacement therapy (ERT) for G... more Objectives: The original manufacturers recommended dose of enzyme replacement therapy (ERT) for Gaucher disease of 120 units/kg body weight/month is safe and effective. In Israel 30 units/kg/month with comparable safety and efficacy is used. Preliminary observations have raised concern that drug withdrawal/dose reduction after high dose is associated with a relatively rapid deterioration in disease parameters, findings not observed on lower doses. We speculated that this differential might be due to down-regulation of endogenous expression of the GBA gene induced by higher concentration of exogenous enzyme.
Journal of Child Neurology, 1995
We studied the seizure and polygraphic patterns of 18 patients with Angelman's sy... more We studied the seizure and polygraphic patterns of 18 patients with Angelman's syndrome. All patients showed movement problems. Eleven patients were also reported to have long-lasting periods of jerky movements. The polygraphic recording showed a myoclonic status epilepticus in nine of them. Seven patients had partial seizures with eye deviation and vomiting, similar to those of childhood occipital epilepsies. These seizures and electroencephalographic patterns suggest that Angelman's syndrome occurs in most of the patients as a nonprogressive, age-dependent myoclonic encephalopathy with a prominent occipital involvement. These findings indicate that, whereas ataxia is a constant symptom in Angelman's syndrome, the occurrence of a transient myoclonic status epilepticus may account for the recurrence of different abnormal movements, namely the jerky ones.
Analytical Biochemistry, 1990
Molecular Genetics and Metabolism, 2015
Objectives. Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that i... more Objectives. Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that individuals with Morquio A syndrome show substantial impairment in multiple domains including endurance and respiratory function (Harmatz et al, Mol Genet Metab, 2013). Here, 1-and 2-year longitudinal endurance and respiratory function data are presented.
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Papers by Rossella Parini