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1.
Neuromuscul Disord ; 25(5): 423-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25728520

ABSTRACT

Adult Polyglucosan Body Disease (APBD) is a rare inherited leukodystrophy associated with axonal polyneuropathy, mainly reported in persons of Ashkenazi-Jewish descent. We describe three Italian siblings at disease onset, presenting in their fifties with a combination of pyramidal and ataxic signs, mild demyelinating neuropathy on neurophysiological investigation (1/3 cases) and transient symptoms (1/3). A leucoencephalopathy with infratentorial lesions without enhancement and medullary/spine atrophy was demonstrated on brain/spine MRI (3/3). Muscle biopsy was normal in 2/3; both muscle and nerve biopsy showed polyglucosan bodies in the sibling with polyneuropathy. This indicated a need for GBE1 sequencing, which revealed a novel missense mutation (c.1064G>A; p.Arg355His) and one previously described (c.1604A>G; p.Tyr535Cys) in all siblings. We highlight that peripheral neuropathy, deemed as disease hallmark, may be missing and that transient symptoms are confirmed as early disease manifestations. The pattern of damage at neuro-imaging described recurs irrespective of clinical presentation, constituting a unifying diagnostic clue.


Subject(s)
Glycogen Storage Disease/diagnosis , Nervous System Diseases/diagnosis , Family , Female , Glycogen Storage Disease/pathology , Glycogen Storage Disease/physiopathology , Humans , Italy , Male , Middle Aged , Muscle, Skeletal/innervation , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Myelin Sheath/pathology , Nervous System Diseases/pathology , Nervous System Diseases/physiopathology , Neural Conduction , Pedigree , Sural Nerve/metabolism , Sural Nerve/pathology , White People
2.
Neuromuscul Disord ; 24(3): 272-6, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24380807

ABSTRACT

Adult polyglucosan body disease is a rare autosomal recessive disease, caused by glycogen branching enzyme gene mutations, characterised by urinary dysfunction, spastic paraplegia with vibration sense loss, peripheral neuropathy, and cognitive impairment. Fabry's disease is an X-linked lysosomal storage disorder caused by α-galactosidase A gene mutations; neurological manifestations include cerebrovascular accidents, small-fibre neuropathy and autonomic dysfunction. Here, we report the case of a 44-year-old Sicilian male with stroke-like episodes, hypohidrosis and mild proteinuria, which led to the diagnosis of Fabry's disease after a hemizygous mutation (p.Ala143Thr) in α-galactosidase A gene was detected. Subsequently, he developed progressive walking difficulties and dementia, which were considered atypical for Fabry's disease. Therefore, we performed additional investigations that eventually led to the diagnosis of adult polyglucosan body disease caused by two novel missense mutations (p.Asp413His and p.Gly534Val) in the glycogen branching enzyme gene. Recently, the pathogenic role of the p.Ala143Thr mutation in causing Fabry's disease has been questioned. This case underlines the importance of performing further investigations when facing with atypical features even in the presence of a genetic diagnosis of a rare disease.


Subject(s)
Diagnostic Errors , Fabry Disease/diagnosis , Glycogen Storage Disease/diagnosis , Nervous System Diseases/diagnosis , Adult , Fabry Disease/genetics , Glycogen Storage Disease/genetics , Humans , Male , Nervous System Diseases/genetics
3.
Eur J Clin Nutr ; 63(1): 106-12, 2009 Jan.
Article in English | MEDLINE | ID: mdl-17717532

ABSTRACT

OBJECTIVES: To investigate the antioxidative properties of sulfurous drinking water after a standard hydropinic treatment (500 ml day(-1) for 2 weeks). SUBJECTS/METHODS: Forty apparently healthy adults, 18 men and 22 women, age 41-55 years old. The antioxidant profile and the oxidative condition were evaluated in healthy subjects supplemented for 2 weeks with (study group) or without (controls) sulfurous mineral water both before (T0) and after (T1) treatment. RESULTS: At T1, a significant decrease (P<0.05) in both lipid and protein oxidation products, namely malondialdehyde, carbonyls and AOPP, was found in plasma samples from subjects drinking sulfurous water with respect to controls. Concomitantly, a significant increment (P<0.05) of the total antioxidant capacity of plasma as well as of total plasmatic thiol levels was evidenced. Tocopherols, carotenoids and retinol remained almost unchanged before and after treatment in both groups. CONCLUSIONS: The improved body redox status in healthy volunteers undergoing a cycle of hydropinic therapy suggests major benefits from sulfurous water consumption in reducing biomolecule oxidation, possibly furnishing valid protection against oxidative damage commonly associated with aging and age-related degenerative diseases.


Subject(s)
Antioxidants/pharmacology , Hydrogen Sulfide/pharmacology , Lipid Peroxidation/drug effects , Mineral Waters , Proteins/metabolism , Adult , Antioxidants/therapeutic use , Female , Humans , Hydrogen Sulfide/therapeutic use , Male , Middle Aged , Mineral Waters/therapeutic use , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects , Water/chemistry
4.
J Neurol Sci ; 275(1-2): 159-63, 2008 Dec 15.
Article in English | MEDLINE | ID: mdl-18804219

ABSTRACT

Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystemic disorder caused by a CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene. We present a three first-degree relative Italian family (proband, his mother and his sister) with a mild DM2 phenotype associated with a short (CCTG)(100) expansion as far as regards the proband and his mother, while his sister shows larger expansion correlated to a more severe phenotype. FISH analysis with (CAGG)(5) probe demonstrated that nuclear foci of mutant RNA were present in the proband muscle and co-localized with muscleblind-like proteins, determining their sequestration in the nucleus. This is one of the smallest expansion reported and the shortest with the evidence of nuclear foci. These data contribute to the clinical and molecular correlation of ZNF9 gene short expansion.


Subject(s)
DNA Repeat Expansion/genetics , Intranuclear Inclusion Bodies/pathology , Myotonic Dystrophy/genetics , Myotonic Dystrophy/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Adult , Creatine Kinase/blood , Electromyography , Family Health , Female , Humans , Indoles , Male , Middle Aged , Muscle, Skeletal/pathology
5.
Acta Myol ; 26(1): 72-4, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17915576

ABSTRACT

Deficiency of debrancher enzyme causes Glycogen Storage Disease (GSD) type III, an autosomal recessive disorder, characterized by tissue accumulation of abnormally structured glycogen. This report reviews current clinical and molecular knowledge about this disorder and describes the variability at phenotype and genotype levels of a large group of Italian GSDIII patients.


Subject(s)
Glycogen Debranching Enzyme System/genetics , Glycogen Storage Disease Type III/genetics , Glycogen Storage Disease Type III/physiopathology , Diet , Female , Genotype , Glycogen Storage Disease Type III/enzymology , Glycogen Storage Disease Type III/therapy , Humans , Italy , Male , Phenotype
6.
Hum Mutat ; 27(6): 600-1, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16705713

ABSTRACT

Glycogenosis type III (Cori disease) is an autosomal recessive disorder caused by the deficiency of the glycogen debranching enzyme, encoded by the AGL gene, and existing in six isoforms alternately spliced in a tissue-specific way. Generally, disease onset occurs early on starting from the first year of life, with hepatomegaly, hypoglycemia, hyperlipidemia, increased CK levels, and, in some cases, short stature and slight mental retardation. Frequently, hepatomegaly tends to resolve spontaneously and inexplicably during childhood, when myopathy, often associated with cardiomyopathy, arises. This disease is known to lack almost invariably clear links between the genotype and clinical phenotype. We describe nine new mutations in Italian patients: four nonsense (p.Arg285X, p.Lys422X, p.Arg910X, p.Arg977X), three frameshift (c.442delA, c.753_756delGACA, c.3963delG), and two missense (p.Ala1120Pro, p.Arg524His). Particularly, the nonsense p.Arg285X is linked to an exonic splicing enhancer and it was found to produce two species of transcripts at the same time. Moreover, we discuss a subgroup of subjects carrying c.2681+1G>A, which has proven to be the most frequent mutation among our patients. The previously described c.664+3A>G was also detected in two patients, both homozygous. The present work is yet another confirmation that the individual genetic background plays a pivotal role in influencing the phenotypes, as occurs in other metabolic diseases.


Subject(s)
Glycogen Debranching Enzyme System/genetics , Glycogen Storage Disease Type III/diagnosis , Mutation , Adult , Amino Acid Sequence , Child , Child, Preschool , Codon, Nonsense , DNA Mutational Analysis , Female , Frameshift Mutation , Glycogen Debranching Enzyme System/chemistry , Glycogen Storage Disease Type III/classification , Glycogen Storage Disease Type III/genetics , Hepatomegaly/genetics , Humans , Italy , Male , Middle Aged , Molecular Sequence Data , Muscular Diseases/genetics , Mutation, Missense , Phenotype , Sequence Alignment
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