informer

Glycogen storage disease type II (GSDII, Pompe disease) is a rare metabolic disorder caused by a deficiency of acid alpha-glucosidase (GAA), an enzyme localized within lysosomes that is solely responsible for glycogen degradation in this compartment. The manifestations of GSDII are heterogeneous but are classified as early or late onset. The natural course of early-onset Pompe disease (EOPD) is severe and rapidly fatal if left untreated. Currently, one therapeutic approach, namely, enzyme replacement therapy, is available, but advances in molecular medicine approaches hold promise for even more effective therapeutic strategies. These approaches, which we review here, comprise splicing modification by antisense oligonucleotides, chaperone therapy, stop codon readthrough therapy, and the use of viral vectors to introduce wild-type genes. Considering the high rate at which innovations are translated from bench to bedside, it is reasonable to expect substantial improvements in the treatment of this illness in the foreseeable future. For more information click here.

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is an autosomal dominant disease caused by mutations in the transthyretin gene, with the most common mutation being V30M (single amino acid substitution of methionine for valine at position 30). Although each TTR variant has a different clinical presentation, peripheral neuropathy and cardiomyopathy are the most common manifestations. Renal impairment is not quite common. Initially thought to be a disease of benign evolution with respect to the kidneys, it was later found that progression to end-stage renal disease occurs in 10% of patients as a natural course of the disease. The detection and prognosis of TTR-FAP nephropathy depend on the presence of albuminuria and increased serum creatinine. Vegetative dysfunction, manifested as sexual disorders or urinary infections, is also common. Nephropathy does not correlate with age, duration of disease or severity of neuropathy. We hereby present a case report of a patient with TTR-FAP, genetically proven by DNA analysis, followed up at the Nephrology Department, University Hospital “St. George”, Plovdiv, for a period of 4 years. For more information click here.

Phenylketonuria (PKU) is a metabolic condition which, left untreated, results in severe and irreversible brain damage. New-born screening and the development of the low phenylalanine (Phe) diet have transformed the outcomes for people with PKU. Those who have benefited from early treatment are now approaching their fifth and sixth decade. It is therefore timely to consider multi-morbidity in PKU and the effects of ageing, in parallel with the wider benefits of emerging treatment options in addition to dietary relaxation. We have conducted the first literature review of co-morbidity and ageing in the context of PKU. Avenues explored have emerged from limited study of multi-morbidity to date and the knowledge and critical enquiry of the authors. Findings suggest PKU to have a wider impact than brain development, and result in several intriguing questions that require investigation to attain the best outcomes for people with PKU in adulthood moving through to older age. We recognise the difficulty in studying longitudinal outcomes in rare disease and emphasise the necessity to develop PKU registries and cohorts that facilitate well designed studies to answer some of the questions raised in this review. Whilst awaiting new information in these areas we propose that clinicians engage with patients to make personalised and well-informed decisions around Phe control and assessment for co-morbidity. For more information click here.