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We report on three cases of infantile Krabbe disease and one case of infantile metachromatic leukodystrophy showing magnetic resonance (MR) imaging findings of diffuse and coexistent cranial nerve and cauda equina nerve roots enhancement. Such findings may be simultaneous, or even precede, typical white matter abnormalities and, in the appropriate clinical context, may facilitate an earlier diagnosis. There is a rational for the use of contrast agents and craniospinal MR imaging during the first imaging of children with a history of psychomotor regression and clinical evidence of peripheral nerve involvement to exclude differential diagnoses. [ABSTRACT FROM AUTHOR]

Pelizaeus–Merzbacher disease (PMD) is an X-linked myelination disorder most frequently caused by duplication of a genomic segment of variable length containing the PLP1 gene. We studied five PMD male patients affected by the classic PMD form carrying a PLP1 gene duplication. On the basis of clinical and neuroradiological features, two of the five patients appeared to be the most severely affected. In order to establish a possible genotype–phenotype correlation, the extent of the duplication was determined in each patient and in the respective mother by quantifying the copy number of genomic markers surrounding the PLP1 gene by a real-time PCR-based approach. Duplications, ranging in size from 167–195 to 580–700 kb, were in the same genomic interval of the majority of the reported duplications. The extent of the duplicated genomic segments does not correlate with the clinical severity. Interestingly enough, each duplication had one of the two breakpoints in or near to low copy repeats (LCRs), supporting recent evidence concerning a possible role of LCRs in the generation of the duplications in PMD. [ABSTRACT FROM AUTHOR]

Alexander disease (AD), a rare neurodegenerative disorder of the central nervous system, is characterized by the accumulation of cytoplasmic protein aggregates (Rosenthal fibers) composed of glial fibrillary acidic protein (GFAP) and small heat-shock proteins within astrocytes. To date, more than 40 different GFAP mutations have been reported in AD. The present study is aimed at the molecular diagnosis of Italian patients suspected to be affected by AD. By analyzing the GFAP gene of 13 unrelated patients (eight with infantile form, two with juvenile form and three with adult form), we found 11 different alleles, including four new ones. Among the novel mutations, three (p.R70Q, p.R73K, and p.R79P) were identified in exon 1 and p.L359P in exon 6. The sequence analysis also detected six different single nucleotide polymorphic variants, including two previously unreported ones, spread throughout non-coding regions (introns 2, 3, 5, 6, and 3′UTR) of the gene. All patients were heterozygous for the mutations, thus confirming their dominant effect. [ABSTRACT FROM AUTHOR]

The present study reports two Italian brothers affected by severe Salla disease (sialic acid storage disease), a slowly progressive autosomal recessive neurodegenerative disorder prevalent in the Finnish population. Mutations of the SLC17A5 gene, which encodes a protein called sialin, are the primary cause of both Salla disease and infantile sialic acid storage disease (ISSD), a clinically distinct severe disorder. All Finnish patients with Salla disease show a R39C mutation. Both patients showed moderate intellectual disability, spastic ataxic syndrome, hypomyelination and cerebellar atrophy on magnetic resonance imaging (MRI), and lysosomal storage, all typical of Salla disease. Mutation analysis of the SLC17A5 gene in the younger brother revealed no R39C mutation, but a 15-bp deletion in exon 6 on one of the alleles. This mutation is the same described in French-Canadian patients with ISSD. Salla disease must be suspected in patients with unexplained psychomotor retardation associated with ataxia and/or pyramidal symptoms, and MRI findings consistent with cerebral hypomyelination, irrespective of the patient's ethnic origin. A mutation screening based on R39C change does not exclude Salla disease outside Finland. Conversely, mutations found in ISSD can be expected, even in patients showing the Salla phenotype (e.g. symptoms at the milder end of the spectrum). [ABSTRACT FROM AUTHOR]

We reviewed the clinical and EEG features of 30 Italian patients with childhood-onset neuronal ceroid lipofuscinosis (NCL). The outcome and the EEG pattern of the 4 infantile NCL cases were classic, although the age at onset of symptoms varied from 1.0 to 3.5 years. This latter finding is unusual and has not been reported for other Italian patients. Both typical and variant cases of late-infantile NCL (LINCL) were observed. This NCL type represents the most common form in our country, and was the largest group (18 cases) in our study. A particular pseudoperiodic EEG pattern was observed in 15 of the 18 patients with LINCL. This pattern may be useful in early diagnosis, especially if associated with the absence of sleep spindles. In the 8 cases with juvenile NCL, clinical and EEG findings were similar to those reported in the literature. [ABSTRACT FROM AUTHOR]

Highlights: [•] Novel mutations in FAM126A have been identified. [•] Further genotype-phenotype correlations of HCC (OMIM #610532) have been defined. [•] FAM126A missense mutations are likely to preserve some neurological functions. [ABSTRACT FROM AUTHOR]

Autosomal recessive hereditary spastic paraplegia with thinning of the anterior corpus callosum (ARHSP-TCC) due to mutations in SPGJJ on chromosome 15q (M1M610844) is the single most common cause ofARHSP. It is characterized by slowly progressive paraparesis and peripheral neuropathy. Although cognitive impairment, sometimes diagnosed as mental retardation, is an almost invariable feature, the extent and specific neuropsychological features are not fully understood. We report a comprehensive neuropsychological assessment in two ARHSP-TCC patients harbouring mutations in SPGJ1. A specific impairment in executive functions occurring even before cognitive decline, may be considered the core of the neuropsychological profile of patients harbouring mutations in SPG11. [ABSTRACT FROM AUTHOR]

Abstract: Mutations in POMT1 and POMT2 genes were originally identified in Walker–Warburg syndrome (WWS) and subsequently reported in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without ocular malformations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystrophy (CMD) patients with α-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known forms of CMD with α-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occur in CMD patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutations in POMT1 and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in POMT1 and six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in patients with mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypoplasia was also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with frontal cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a WWS phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible for the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 is ample and the spectrum of associated phenotypes is wider than initially thought. [Copyright &y& Elsevier]

A letter to the editor discussing identification and functional characterization of c.462delA mutation of the CI subunit gene NADH dehydrogenase (ubiquinone) Fe-S protein 4 (NDUFS4) in two siblings with Leigh syndrome is presented.

Recent legislation has made mandatory to perform the risk assessment taking into account gender differences. This should imply to consider not only the simple differences due to biologic difference between male and female workers, but also what is more related to the social role they really play in the current society. This second aspect of gender difference has not yet been addressed from a technical point of view. The University of Pisa in cooperation with INAIL has recently started a project aimed at identifying technical tools to perform a risk assessment which took into account gender difference. [ABSTRACT FROM AUTHOR]