Maria Alice Donati
A5039295512- Metabolism and Genetic Disorders
- Lysosomal Storage Disorders Research
- Mitochondrial Function and Pathology
- Glycogen Storage Diseases and Myoclonus
- Neonatal Health and Biochemistry
- Muscle Physiology and Disorders
- Amino Acid Enzymes and Metabolism
- Biochemical and Molecular Research
- RNA modifications and cancer
- Trypanosoma species research and implications
- Folate and B Vitamins Research
- Cardiomyopathy and Myosin Studies
- Neurogenetic and Muscular Disorders Research
- ATP Synthase and ATPases Research
- Genomics and Rare Diseases
- Cellular transport and secretion
- Carbohydrate Chemistry and Synthesis
- Diet and metabolism studies
- Genetics and Neurodevelopmental Disorders
- Biotin and Related Studies
- Genetic Neurodegenerative Diseases
- RNA regulation and disease
- Children's Physical and Motor Development
- Cerebral Palsy and Movement Disorders
- RNA and protein synthesis mechanisms
Meyer Children's Hospital
2015-2024
University of Florence
2011-2023
Centro Clinico Nemo
2022
Università Cattolica del Sacro Cuore
2022
Agostino Gemelli University Polyclinic
2022
Sapienza University of Rome
2022
Temple Street Children's University Hospital
2022
Fondazione Stella Maris
2017-2019
University of Siena
1997-2019
University of Verona
2019
Abstract We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, 50 disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in transfer RNA Leu(UUR) gene DNA. found high concordance between clinical diagnosis MELAS mutation, which was present 21 MELAS, all 11 12 14 but only five without MELAS. The proportion...
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder defined clinically by severe gastrointestinal dysmotility; cachexia; ptosis, ophthalmoparesis, or both; peripheral neuropathy; leukoencephalopathy; and mitochondrial abnormalities. The disease caused mutations in the thymidine phosphorylase (TP) gene. TP protein catalyzes phosphorolysis of to thymine deoxyribose 1-phosphate. We identified 21 probands (35 patients) who fulfilled our clinical...
Mitochondrialneurogastrointestinalencephalomyopathy (MNGIE) is an autosomal recessive human disease due to mutations in the thymidine phosphorylase (TP) gene. TP enzyme catalyzes reversible phosphorolysis of thymine and 2-deoxy-d-ribose 1-phosphate. We present evidence that metabolism altered MNGIE. activities buffy coats were reduced drastically all 27 MNGIE patients compared with 19 controls. All had much higher plasma levels than normal individuals asymptomatic mutation carriers. In two...
Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 with tyrosine reviewed the literature. Based presenting neurological features, can be divided two phenotypes: infantile onset, progressive,...
The aim of the study was to assess different outcome measures in a cohort ambulant boys with Duchenne muscular dystrophy (DMD) over 12 months order establish spectrum possible changes relation age and steroid treatment.The is longitudinal multicentric study. A total 106 patients DMD were assessed using 6-minute walk test (6MWT) North Star Ambulatory Assessment (NSAA) at baseline months. Clinical data including treatment collected.During study, we observed mean decline 25.8 meters 6MWT SD...
The 6 minute walk test has been recently chosen as the primary outcome measure in international multicenter clinical trials Duchenne muscular dystrophy ambulant patients. aim of study was to assess spectrum changes at 3 years individual measures, their correlation with steroid treatment, age and values baseline. Ninety-six patients from 11 centers were assessed baseline 12, 24 36 months after using North Star Ambulatory Assessment. Three boys (3%) lost ability perform within 12 months,...
Objectives The aim of the study was i) to assess spectrum changes over 24 months in ambulant boys affected by Duchenne muscular dystrophy, ii) establish difference between first and second year results iii) identify possible early markers loss ambulation. Methods One hundred thirteen patients (age range 4.1–17, mean 8.2) fulfilled inclusion criteria, 67 113 were on daily 40 intermittent steroids, while 6 not steroids. All assessed using Minute Walk Test (6MWT), North Star Ambulatory...
Thymidine kinase 2, encoded by the nuclear gene TK2, is required for mitochondrial DNA maintenance. Autosomal recessive TK2 mutations cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy usually beginning in childhood progressing relentlessly. We investigated safety efficacy deoxynucleoside monophosphate therapies.We administered monophosphates to 16 TK2-deficient patients under compassionate use program.In 5 with early onset severe disease, survival...
Background Thymine kinase 2 (TK2) is a mitochondrial matrix protein encoded in nuclear DNA and phosphorylates the pyrimidine nucleosides: thymidine deoxycytidine. Autosomal recessive TK2 mutations cause spectrum of disease from infantile onset to adult manifesting primarily as myopathy. Objective To perform retrospective natural history study large cohort patients with deficiency. Methods The was conducted by 42 investigators across 31 academic medical centres. Results We identified 92...
Efficacy and safety of onasemnogene abeparvovec (OA) for Spinal Muscular Atrophy infants under 7 months <8.5 kg has been reported in clinical trials. This study examines efficacy predictors a wide age (22 days-72 months) weight (3.2-17 kg) range, also including patients previously treated with other drugs.46 were 12 between January 2020 March 2022. Safety profile was available another 21 at least 6 month follow-up after OA infusion. 19/67 treatment naïve when OA. Motor function measured the...
Background: Glycogen storage disease type IV (GSD-IV) is a clinically heterogeneous autosomal recessive disorder due to glycogen branching enzyme (GBE) deficiency and resulting in the accumulation of an amylopectin-like polysaccharide. The typical presentation liver childhood, progressing lethal cirrhosis. neuromuscular form GSD-IV varies onset (perinatal, congenital, juvenile, or adult) severity. Objective: To identify molecular bases different forms establish possible genotype/phenotype...
Abstract Background: The expansion of newborn screening programs has increased the number newborns diagnosed with inborn errors metabolism in presymptomatic phase, but it also costly, stress-producing false-positive results. Because propionylcarnitine (C3) is one analytes most frequently responsible for results, we aimed to develop a rapid liquid chromatography–tandem mass spectrometry (LC-MS/MS) method identify free methylmalonic (MMA) and 3-OH propionic (3OH-PA) acids blood spots. Methods:...
Objective In the last few years some of therapeutical approaches for Duchenne muscular dystrophy (DMD) are specifically targeting distinct groups mutations, such as deletions eligible skipping individual exons. The aim this observational study was to establish whether patients with mutations have different profiles changes on 6 minute walk test (6MWT) over a 12 month period. Methods 6MWT performed in 191 ambulant DMD boys at baseline and months later. results were analysed using...
Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize recombinant enzyme used therapy. Here, we evaluated effects a combination chaperone on activity disease patients. α-Glucosidase was analyzed by tandem-mass spectrometry dried blood spots from patients treated with therapy,...