BackgroundCharcot–Marie–Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to ...determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.MethodsThe genes known to cause CMT were sequenced in 1607 patients with CMT (425 patients attending an inherited neuropathy clinic and 1182 patients whose DNA was sent to the authors for genetic testing) to determine the proportion of different subtypes in a UK population.ResultsA molecular diagnosis was achieved in 62.6% of patients with CMT attending the inherited neuropathy clinic; in 80.4% of patients with CMT1 (demyelinating CMT) and in 25.2% of those with CMT2 (axonal CMT). Mutations or rearrangements in PMP22, GJB1, MPZ and MFN2 accounted for over 90% of the molecular diagnoses while mutations in all other genes tested were rare.ConclusionFour commonly available genes account for over 90% of all CMT molecular diagnoses; a diagnostic algorithm is proposed based on these results for use in clinical practice. Any patient with CMT without a mutation in these four genes or with an unusual phenotype should be considered for referral for an expert opinion to maximise the chance of reaching a molecular diagnosis.
Worldwide, many production supply chains generate a considerable amount of legume by-products (e.g., leaves, husks, broken seeds, defatted cakes). These wastes can be revalorized to develop ...sustainable protein ingredients, with positive economic and environmental effects. To separate protein from legume by-products, a broad spectrum of conventional (e.g., alkaline solubilization, isoelectric precipitation, membrane filtration) and novel methodologies (e.g., ultrasound, high-pressure homogenization, enzymatic approaches) have been studied. In this review, these techniques and their efficiency are discussed in detail. The present paper also provides an overview of the nutritional and functional characteristics of proteins extracted from legume by-products. Moreover, existing challenges and limitations associated with the valorization of by-product proteins are highlighted, and future perspectives are proposed.
Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial ...support, tax credits, and perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs, both for newly developed drugs and for drugs that were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one‐fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington disease, adrenocorticotropic hormone for infantile spasms, and enzyme replacement therapy with alglucosidase alpha for Pompe disease, we highlight these paradoxical effects. ANN NEUROL 2012;72:481–490
Nerve biopsy was previously reported in two of the original families with FAM134B mutations, also showing an axonal neuropathy but with a preference for small myelinated fibres. 3 The nonsense ...mutation found in this patient, c.471C->T (p.Q145X), was described in the original paper in a Turkish family, is predicted to lead to nonsense mediated decay resulting in absence of the protein or a non-functional gene product. 3 This family had onset in the first decade, impaired nociception, ulcerations of hands and feet, and chronic osteomyelitis; however, weakness was not described. ...this report expands the phenotype of HSNII due to mutations in FAM134B emphasising that motor involvement may occur and providing further evidence for the pathogenicity of mutations in FAM134B.
Inherited cerebellar ataxias (CA) are heterogeneous progressive neurological conditions associated with significant functional limitations. This study aimed to assess the implications of inherited CA ...on patients’ self-reported quality of life (QoL) and impairments in work and activities. 129 individuals with ataxia responded to a survey focused on QoL. Health-related QoL was measured using the RAND 36-Item Short Form Survey. An adaptation of the validated Work Productivity and Activity Impairment questionnaire was used to assess the effect of health on work productivity and ability to perform activities over the past week. Nine percent of respondents were currently employed. Individuals with inherited ataxia experienced significant activity impairment, and 75% required professional or informal care. Health-related quality of life (HRQoL) was significantly worse in all areas for the individuals with inherited ataxia compared with Irish population normative values. Participants with Friedreich’s ataxia (
n
= 56) demonstrated worse physical functioning then those with undetermined ataxia (
n
= 55). Female gender, younger age at symptom onset, current employment, retirement due to age or ataxia, and living in a long-term care facility were associated with higher sub-scores in different domains of HRQoL, while disease duration correlated with worse physical functioning sub-scores. This study is the first cross-sectional study on HRQoL in patients with inherited ataxia in Ireland. It highlights high rates of unemployment, difficulty with daily activities and physical functioning limitations, which is worse than comparative international studies. Given the limited therapeutic options currently available, optimising HRQoL is an important aspect of managing ataxia.
BackgroundTay-Sachs disease is a rare, and often fatal, autosomal recessive, lysosomal storage disease. Deficiency in ß-Hexosaminidase A (HEX A) leads to accumulation of GM ganglioside resulting in ...neuronal swelling and degeneration. Typical onset is in infancy with developmental regression and early death. Late-onset Tay-Sachs disease (LOTS) is extremely rare, especially in the non-Ashkenazi Jewish population, and is characterised by a more indolent presentation, typically encompassing features of cer- ebellar and anterior horn cell dysfunction in addition to extrapyramidal and neuropsychiatric symptoms.Case SummariesWe present four adult patients with known LOTS from four unrelated non-consanguineous families. Each had neurophysiological evidence of chronic motor axonal loss in the limbs, accompanied in 2 cases by peripheral sensory axonal loss. Cerebellar atrophy, reported to be a ubiquitous feature on MRI in LOTS, was absent in all cases.DiscussionOur case series supports the existence of a pure neuromuscular phenotype in LOTS. This condition should be considered in the differential diagnosis of anterior horn cell disorders.
Background and purpose
Tay−Sachs disease is a rare and often fatal, autosomal recessive, lysosomal storage disease. Deficiency in β‐hexosaminidase leads to accumulation of GM2 ganglioside resulting ...in neuronal swelling and degeneration. Typical onset is in infancy with developmental regression and early death. Late‐onset Tay−Sachs disease (LOTS) is extremely rare, especially in the non‐Ashkenazi Jewish population, and is characterized by a more indolent presentation typically encompassing features of cerebellar and anterior horn cell dysfunction in addition to extrapyramidal and neuropsychiatric symptoms.
Cases
A case series of four unrelated patients of non‐Ashkenazi Jewish origin with a predominantly, and in some cases pure, neuromuscular phenotype with evidence of a motor neuronopathy on electromyography is presented. Cerebellar atrophy, reported to be a ubiquitous feature in LOTS, was absent in all patients.
Conclusion
This case series provides evidence to support a pure neuromuscular phenotype in LOTS, which should be considered in the differential diagnosis of anterior horn cell disorders.
•Pre-processing influenced extractability and functionality of fava bean protein.•Dehulling is an important step to produce protein with high purity and solubility.•Soaking of beans prior to wet ...milling led to increased protein yield and WAC.
In this study, fava bean protein (FPI) was isolated from flours prepared from dehulled seeds and compared to FPI extracted from whole flours; in the latter case, flours were prepared either by dry- or wet-milling. Significant differences in composition and functionality were observed between the three FPIs produced. Dehulling maximized protein purity, oil-absorption capacity, solubility, foamablity and minimized both starchy and non-starchy carbohydrate contents. Protein isolated from wet-milled whole beans provided higher mass and extraction yields, better water-absorption capacity, and exhibited higher surface charge (zeta potential) compared to other samples. The protein extracted from dry-milled whole seed exhibited a higher least gelation concentration, emulsifying activity and zeta value compared to its dehulled counterpart. Dehulling was also found to be a useful process to increase the lightness/whiteness of protein powder. Overall, the present findings provide useful technological information relating to the production of FPI with and without a dehulling step.
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