Late-onset Form Of Disease Research Articles

Genetic analysis of 76 Spanish Pompe disease patients: Identification of 12 novel pathogenic GAA variants and functional characterization of splicing variants.

Glycogenosis type II (GSDII), or Pompe disease (MIM 232300), is an inherited autosomal recessive disorder caused by deficiency of the lysosomal acid-α-glucosidase. Mutations in the GAA gene alter normal enzyme production and lead to progressive buildup of intralysosomal glycogen, which plays an essential role in the severity and progression of the disease. We report here the study of 76 patients from Spain with either infantile or late onset form of Pompe disease. The analysis consisted in the molecular study of exons and intron flanking fragments of GAA gene. We have identified 55 different molecular pathogenic variants, 12 of them not previously described. In addition, we have determined a frequency of 84.37% for the c.-32-13T>G mutation in patients with the late-onset form of the disease. Functional characterization of some splice mutations showed deleterious mechanisms on the processing of mRNA.

Patient and caregiver perspectives on burden of disease manifestations in late-onset Tay-Sachs and Sandhoff diseases

BackgroundThe GM2 gangliosidoses (GM2), Tay-Sachs and Sandhoff diseases, are rare, autosomal recessive genetic disorders caused by mutations in the lysosomal enzyme β-hexosaminidase A (HEXA) or β-hexosaminidase B (HEXB) genes, respectively. A minority of patients have a late-onset form of disease that presents from late-childhood to adulthood and has a slowly progressive course with prolonged survival.Little research has been published documenting patient experiences with late-onset Tay-Sachs and Sandhoff diseases and how the disease impacts their daily lives and functioning. This study explored the most frequent symptoms and functional impacts experienced by patients with late-onset GM2 gangliosidosis through interviews with patients and caregivers.MethodsA qualitative research study design was employed, using three focus groups and 18 one-on-one interviews with patients who were recruited at the National Tay-Sachs and Allied Diseases Annual Family Conference. Transcripts were generated from the discussions, and patient quotes were analyzed using a content analysis approach. Concepts were aggregated into symptom and functional impacts, and the frequency of mention in the focus groups and individual interviews was calculated.Key findingsMany of the frequently described symptoms [muscle weakness (n = 19, 95%), “clumsy” gait (n = 12, 60%), fatigue (n = 10, 50%)] and impacts [difficulty walking (n = 19, 95%), falling (n = 17, 85%), and climbing stairs (n = 16, 80%)] disclosed by patients and caregivers were similar to those previously reported in the literature. However, less frequently described symptoms such as gastrointestinal issues (n = 4, 20%) and coughing fits (n = 5, 25%) have been expanded upon. This study evaluated the immediate impact of these symptoms on the patients’ lives to highlight the burden of these symptoms and the functional limitations on daily living activities, independence, and emotional well-being. The findings were used to develop a conceptual disease model that could serve as a foundation for patient-centered outcomes in clinical trials and provide insights to the medical community that may benefit patient care.ConclusionsThis study contributes to the current understanding of symptoms associated with late-onset GM2 gangliosidosis, and further identifies the many consequences and impacts of the disease. These symptoms and impacts could be measured in clinical trials to examine the effects of novel treatments from the patient perspective.

Amyotrophy, cerebellar impairment and psychiatric disease are the main symptoms in a cohort of 14 Czech patients with the late-onset form of Tay-Sachs disease.

Tay-Sachs disease (TSD) is an inherited neurodegenerative disorder caused by a lysosomal β-hexosaminidase A deficiency due to mutations in the HEXA gene. The late-onset form of disease (LOTS) is considered rare, and only a limited number of cases have been reported. The clinical course of LOTS differs substantially from classic infantile TSD. Comprehensive data from 14 Czech patients with LOTS were collated, including results of enzyme assays and genetic analyses. 14 patients (9 females, 5 males) with LOTS were diagnosed between 2002 and 2018 in the Czech Republic (a calculated birth prevalence of 1 per 325,175 live births). The median age of first symptoms was 21years (range 10-33years), and the median diagnostic delay was 10.5years (range 0-29years). The main clinical symptoms at the time of manifestation were stammering or slurred speech, proximal weakness of the lower extremities due to anterior horn cell neuronopathy, signs of neo- and paleocerebellar dysfunction and/or psychiatric disorders. Cerebellar atrophy detected through brain MRI was a common finding. Residual enzyme activity was 1.8-4.1% of controls. All patients carried the typical LOTS-associated c.805G>A (p.Gly269Ser) mutation on at least one allele, while a novel point mutation, c.754C>T (p.Arg252Cys) was found in two siblings. LOTS seems to be an underdiagnosed cause of progressive distal motor neuron disease, with variably expressed cerebellar impairment and psychiatric symptomatology in our group of adolescent and adult patients. The enzyme assay of β-hexosaminidase A in serum/plasma is a rapid and reliable tool to verify clinical suspicions.

Otorhinolaryngological, audiovestibular and swallowing manifestations of patients with Niemann–Pick disease Type C

ObjectivesThe aim of this study is to evaluate audiovestibular and swallowing impairment of patients with NPC. MethodsAudiovestibular and swallowing evaluation were performed on patients with Niemann–Pick disease type C (NPC) at Hacettepe University between 20013 and 2015 prospectively. Pure-tone audiometry (PTA), Auditory Brain stem response (ABR), Flexible endoscopic evaluation of swallowing (FEES) test and posturography were done. Hearing, swallowing and balance states were measured. ResultsThere were 16 patients (5 male and 11 female, with a median age of 6.5 years old). The most common ABR abnormalities observed were absent waves I and III (%70 absent I waves, %43.75 absent III waves). Twelve of sixteen patients (%75) had an ABR abnormality in at least one ear, of these, four patients had normal hearing and three of them had periferal hearing loss. 12 (75%) patients had complaint of postural imbalance. 11(69%) of patients had peripheral and one (6%) patient had central impairment. Nine of sixteen patients (56.25%) show some degree of dysphagia (either penetration or aspiration). Two patients (12.5%) showed aspiration both liquid and viscous nutrition. Three patients (18.75%) showed aspiration primarily in liquids and two of them had penetration with viscous nutrition. Three patients (18.75%) had penetration with no aspiration neither liquid nor viscous nutrition (PEN-ASP score was 3, 3, 5, respectively). ConclusionThere is no curative treatment for this devastating and fatal disorder and hearing impairment, balance and swallowing disorders can be seen especially late onset form of disease.

Selective White Matter Involvement in a Patient with Late Onset Krabbe Disease: MR, MR Spectroscopy, and Diffusion Tensor Study

The most frequent type of Krabbe disease has an infantile onset. Unusual slowly progressive adult forms have also been described. We described a different involvement of white matter tracts where magnetic resonance signal alterations were evident in a case of a patient affected by late-onset form of disease.

Listeriosis during pregnancy.

Listeriosis is an uncommon infection that has a unique predilection for pregnant women and may result in pregnancy loss. Contaminated food is the usual source of infection, and increased federal surveillance of foodstuffs is the most effective strategy for prevention of disease. Although dramatic epidemics have received the most publicity, more cases of perinatal listeriosis are isolated. If Listeria chorioamnionitis is diagnosed preterm, in contrast to other types of chorioamnionitis, in utero therapy with high-dose penicillin or trimethoprim-sulfamethoxazole is possible, and preterm delivery may be avoided. The clinical characteristics of neonatal listeriosis are similar to neonatal Group B Streptococcus sepsis, with early and late onset forms of disease. The epidemiology, diagnosis, and management of Listeria infection in pregnancy are reviewed.

GENERALIZED PARESIS IN A 15-YEAR-OLD GIRL.

GENERALIZED paresis of insane and late manifestations of congenital syphilis were at one time relatively common clinical problems. Today remaining handful of patients with generalized paresis inhabit back wards of state mental hospitals, and congenital syphilis is seen infrequently in newborns and almost never as late onset form of disease. With discovery of penicillin, and subsequent relative decline in number of cases of syphilis being seen by private practitioner, there has been a tendency to omit serological test for syphilis from routine prenatal examination. In past few years syphilis has been on increase, particularly in 15- to 25-year-age group—the early reproductive years. It is by reputation the great imitator, and unless suspected and looked for, it will be missed. The occurrence of late-onset congenital syphilis manifesting itself as generalized paresis is a rare situation. This