Biomedical subjects

Deyanira Corzo

Publications and source records attributed to Deyanira Corzo.

5 recordsLinked to original sources

PubMed2006

A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease.

OBJECTIVE: To characterize the natural progression of infantile-onset Pompe disease. STUDY DESIGN: Retrospective chart reviews of 168 patients with documented acid alpha-glucosidase deficiency and symptom onset by 12 months of age; Kaplan-Meier analysis of total and ventilator-free survival time; Cox proportional hazards regression modeling of mortality risk factors. RESULTS: The median age at symptom onset was 2.0 months (range 0 to 12 months), 4.7 months at diagnosis (range: prenatal to 4.2 months), 5.9 months at first ventilator support (range 0.1 to 31.1 months), and 8.7 months at death (range 0.3 to 73.4 months). Survival rates at 12 months of age were 25.7% overall and 16.9% ventilator-free; at 18 months 12.3% and 6.7%. Cardiomegaly (92%), hypotonia (88%), cardiomyopathy (88%), respiratory distress (78%), muscle weakness (63%), feeding difficulties (57%), and failure to thrive (53%) appeared after a median age of approximately 4.0 months. Multiple covariate analysis confirmed that early symptom onset increased risk of early death. CONCLUSION: Despite frequent therapeutic interventions, infantile-onset Pompe disease remains lethal.

Cohort Studies↗

PubMed2006

Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.

OBJECTIVE: To conduct an open-label, multinational, multicenter study examining the safety and efficacy of recombinant human acid alpha-glucosidase (rhGAA) in treatment of infantile-onset Pompe disease. STUDY DESIGN: We enrolled 8 infant patients who had Pompe disease with GAA activity <1% of normal, cardiomyopathy, and hypotonia. In the 52-week initial phase, rhGAA was infused intravenously at 10 mg/kg weekly; an extension phase continued survivors' treatment with 10 to 20 mg/kg of rhGAA weekly or 20 mg/kg every 2 weeks for as long as 153 weeks. Safety measurements included adverse events, laboratory tests, and anti-rhGAA antibody titers. Efficacy evaluations included survival, ventilator use, echocardiograms, growth, and motor and cognitive function. RESULT: After 52 weeks of treatment, 6 of 8 patients were alive, and 5 patients were free of invasive ventilator support. Clinical improvements included ameliorated cardiomyopathy and improved growth and cognition. Five patients acquired new motor milestones; 3 patients walked independently. Four patients died after the initial study phase; the median age at death or treatment withdrawal for all patients was 21.7 months, significantly later than expected for patients who were not treated. Treatment was safe and well tolerated; no death was drug-related. CONCLUSION: rhGAA improved ventilator-free survival, cardiomyopathy, growth, and motor function in patients with infantile-onset Pompe disease compared with outcomes expected for patients without treatment.

Body Height↗

PubMed2005

A computer adaptive testing approach for assessing physical functioning in children and adolescents.

The purpose of this article is to demonstrate: (1) the accuracy and (2) the reduction in amount of time and effort in assessing physical functioning (self-care and mobility domains) of children and adolescents using computer-adaptive testing (CAT). A CAT algorithm selects questions directly tailored to the child's ability level, based on previous responses. Using a CAT algorithm, a simulation study was used to determine the number of items necessary to approximate the score of a full-length assessment. We built simulated CAT (5-, 10-, 15-, and 20-item versions) for self-care and mobility domains and tested their accuracy in a normative sample (n=373; 190 males, 183 females; mean age 6y 11mo [SD 4y 2m], range 4mo to 14y 11mo) and a sample of children and adolescents with Pompe disease (n=26; 21 males, 5 females; mean age 6y 1mo [SD 3y 10mo], range 5mo to 14y 10mo). Results indicated that comparable score estimates (based on computer simulations) to the full-length tests can be achieved in a 20-item CAT version for all age ranges and for normative and clinical samples. No more than 13 to 16% of the items in the full-length tests were needed for any one administration. These results support further consideration of using CAT programs for accurate and efficient clinical assessments of physical functioning.

Activities of Daily Living↗

PubMed2004

Nephrotic syndrome complicating alpha-glucosidase replacement therapy for Pompe disease.

We report a patient with Pompe disease who developed reversible nephrotic syndrome during prolonged, high-dose, experimental, enzyme replacement therapy with recombinant human acid alpha-glucosidase (rhGAA). Because of the development of antibodies to rhGAA and concomitant clinical decline, escalating doses of rhGAA were administered as part of an experimental immune tolerance regimen. Histologic evaluation of kidney tissue revealed glomerular deposition of immune complexes containing rhGAA itself, in a pattern of membranous nephropathy. To our knowledge, this is the first reported case of nephrotic syndrome occurring during enzyme replacement therapy. The nephrotic syndrome gradually resolved after the rhGAA dose was decreased, indicating that decreasing the antigenic load can ameliorate glomerular immune complex deposition associated with enzyme replacement in a highly sensitized patient.

Antibodies↗

PubMed2002

Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E: a novel neonatal phenotype similar to peroxisomal biogenesis disorders.

X-linked adrenoleukodystrophy (X-ALD) results from mutations in ABCD1. ABCD1 resides on Xq28 and encodes an integral peroxisomal membrane protein (ALD protein [ALDP]) that is of unknown function and that belongs to the ATP-binding cassette-transporter superfamily. Individuals with ABCD1 mutations accumulate very-long-chain fatty acids (VLCFA) (carbon length >22). Childhood cerebral X-ALD is the most devastating form of the disease. These children have the earliest onset (age 7.2 +/- 1.7 years) among the clinical phenotypes for ABCD1 mutations, but onset does not occur at <3 years of age. Individuals with either peroxisomal biogenesis disorders (PBD) or single-enzyme deficiencies (SED) in the peroxisomal beta-oxidation pathway--disorders such as acyl CoA oxidase deficiency and bifunctional protein deficiency--also accumulate VLCFA, but they present during the neonatal period. Until now, it has been possible to distinguish unequivocally between individuals with these autosomal recessively inherited syndromes and individuals with ABCD1 mutations, on the basis of the clinical presentation and measurement of other biochemical markers. We have identified three newborn boys who had clinical symptoms and initial biochemical results consistent with PBD or SED. In further study, however, we showed that they lacked ALDP, and we identified deletions that extended into the promoter region of ABCD1 and the neighboring gene, DXS1357E. Mutations in DXS1357E and the ABCD1 promoter region have not been described previously. We propose that the term "contiguous ABCD1 DXS1357E deletion syndrome" (CADDS) be used to identify this new contiguous-gene syndrome. The three patients with CADDS who are described here have important implications for genetic counseling, because individuals with CADDS may previously have been misdiagnosed as having an autosomal recessive PBD or SED

ATP Binding Cassette Transporter, Subfamily D, Mem↗