Showing papers by "Rossella Parini published in 2003"
TL;DR: It is crucial for paediatric Fabry disease patients to have early access to optimal supportive symptomatic management and enzyme replacement therapy should be initiated at an early stage, prior to the onset of irreversible complications.
Abstract: Fabry disease (FD) is a debilitating progressive multisystem X-linked lysosomal storage disorder. It was generally believed that the disease affects only adult males. Through systematic pedigree analysis, we identified 35 paediatric FD patients (age 1 to 21 years, mean 12.6 years) in 25 families. Predominant signs in this cohort were: acroparesthesia, hypohidrosis, and cornea verticillata. Neurological and psychological changes, such as tinnitus, recurrent vertigo, headache, diminished level of activity, fatigue, and depression were often observed. Angiokeratoma and gastrointestinal symptoms were frequent. Some patients also showed cardiac abnormalities. Six children and adolescents (three males and three females) over 14 years of age had renal involvement (all with proteinuria, one male had a decreased creatinine clearance of 62 ml/min). No males, but three females (1.5, 4 and 9 years of age), were free of signs and symptoms. Males (n=15, age 1 to 21 years, mean 12.4 years) and females (n=20, age 1.5 to 20 years, mean 12.7 years) showed comparable disease severity. However, the clinical courses demonstrated a wide intra- and interfamilial variability and tended to be more heterogeneous in the girls. Female patients are frequently affected at an early age, not much differently than males. They should be carefully examined because most carriers are symptomatic. Conclusion: Fabry disease usually becomes clinically manifest in childhood. Renal involvement can begin in adolescence. The diagnosis is made following a high level of suspicion or systematic pedigree analysis. It is crucial for paediatric Fabry disease patients to have early access to optimal supportive symptomatic management. Enzyme replacement therapy has shown promising effectiveness in adults. Considering its widespread therapeutic and potential preventive benefits, enzyme replacement therapy should be initiated at an early stage, prior to the onset of irreversible complications.
201 citations
TL;DR: The classical form is mainly characterised, in affected hemizygous males, by angiokeratoma, acroparaesthesias, hypohidrosis, pains, fever crises, and involvement of the kidneys, brain, and heart, while the cardiac variant is characterised by symptoms restricted to cardiac abnormalities.
Abstract: Anderson-Fabry disease (E C 3.2.1.22, MIM 301500) is an X linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase A (GLA).1,2 The onset of the disease and the severity of clinical manifestations depend principally on residual GLA enzymatic activity.1 Fabry disease can be classified into two clinical phenotypes: the classical form and the cardiac variant.1,3 The classical form is mainly characterised, in affected hemizygous males, by angiokeratoma, acroparaesthesias, hypohidrosis, pains, fever crises, and involvement of the kidneys, brain, and heart. Neurological and/or psychological manifestations with personality disturbances can also occur.1 The cardiac variant is characterised by symptoms restricted to cardiac abnormalities, including conduction defects and/or late onset cardiomyopathy with left ventricular hypertrophy.1,3,4 A prevalence of Fabry disease in a referral population of male patients with a clinical diagnosis of late onset hypertrophic cardiomyopathy (HCM) has also been reported.5 The X linked disorders affect males, while the female carriers are generally asymptomatic, owing in part to the random inactivation of the X chromosome.6 Fabry female carriers can be asymptomatic or clinically affected, usually with a late onset and mild form of the disease. Corneal abnormalities are the most frequent clinical manifestations.1
The human GLA gene, mapped on Xq22, is organised in seven exons encompassing over 12 kb.7 So far, about 265 mutations spread throughout the GLA gene in all exons have been reported in the Human Gene Mutation Database Web site and, in addition, a further 65 have been published.8,9
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62 citations
TL;DR: In this paper, the authors present the case of a newborn infant in the acute stage of the classical form of MSUD in which a remarkable decrease in the water apparent diffusion coefficient (ADC) in advanced myelinating white matter areas was associated with an increase in the T2 signal.
Abstract: Background The acute phase of the neonatal classical form of maple syrup urine disease (MSUD) is usually associated with generalized brain edema. Methods and results The authors present the case of a newborn infant in the acute stage of the classical form of MSUD in whom a remarkable decrease in the water apparent diffusion coefficient (ADC) in advanced myelinating white matter areas was associated with an increase in the T2 signal. This diffusion magnetic resonance imaging (MRI) pattern appears to be compatible with a rare kind of cytotoxic edema, the so-called intramyelinic edema. At the same time, an increase in the ADC was seen in unmyelinated areas together with an increase in the T2 signal, a sign of a coexistent vasogenic-interstitial edema. Conclusions ADC measurements in MSUD provide more specific information than conventional MRI about the pathophysiology of white matter changes.
44 citations
TL;DR: The CliniMACS method is technically feasible and can be successfully used to transplant children with IMSD and it is reported that all patients engrafted at a median time of 12 days and none of the patients developed GVHD.
Abstract: Allogeneic bone marrow stem cell transplantation following CD34+ immunomagnetic enrichment in patients with inherited metabolic storage diseases
33 citations
TL;DR: The molecular characterisation of five unrelated subjects, four Italian and one Tunisian, is reported and the following new mutations are described and confirmed, confirming the genetic heterogeneity of this disease.
Abstract: Total or partial lack of glycogen debranching enzyme (GDE or AGL, amylo-1,6-glucosidase, 4-alpha-glucanotransferase) is responsible for Glycogen Storage Disease type III (GSDIII), a rare autosomal recessive disorder of glycogen metabolism. The clinical and biochemical features of GSDIII subjects are quite heterogeneous, and this mirrors the genotype-phenotype heterogeneity among patients. In this paper, we report the molecular characterisation of five unrelated subjects, four Italian and one Tunisian. The following new mutations are described and confirm the genetic heterogeneity of this disease: p.R864X, p.R428K, c.3911 insA, p.G1087R and c.3512_3549dup+c.3512_3519del. The functional relevance of these mutations is discussed on the basis of the recently acquired knowledge about the boundaries and structures of the two catalytic domains.
21 citations
Journal Article•
TL;DR: The gene, SLC17A5 (MIM 604322), localized on chromosome 6q14-q15 ([2], is a defect in the lysosomal membrane-specific carrier for sialic acid and uronic acids that causes inborn errors of metabolism with autosomal recessive inheritance.
Abstract: Lysosomal free sialic acid storage diseases are rare inborn errors of metabolism with autosomal recessive inheritance that are caused by a defect in the lysosomal membrane-specific carrier for sialic acid and uronic acids ([1][1]). The gene, SLC17A5 (MIM 604322), localized on chromosome 6q14-q15 ([2
18 citations