Clinical Features of Friedreich Ataxia

Friedreich ataxia, the most common hereditary ataxia, affects approximately 1 per 29,000 white individuals. In about 98% of these individuals, it is due to homozygosity for a GAA trinucleotide repeat expansion in intron 1 of FXN; in the other 2%, it is due to compound heterozygosity for a GAA expansion and point mutation or deletion. The condition affects multiple sites in the central and peripheral nervous system as well as a number of other organ systems, resulting in multiple signs and symptoms. Onset of this autosomal recessive condition is usually in the first 2 decades of life. Major clinical features include progressive ataxia, absent lower limb reflexes, upgoing plantar responses, and peripheral sensory neuropathy. The main nonneurological sites of morbidity are the heart, resulting in cardiomyopathy, and the pancreas, resulting in diabetes mellitus. In this review, we provide an overview of the clinical features of Friedreich ataxia and discuss differential diagnoses.

Download Full-text

FRIEDREICH ATAXIA – A CASE REPORT

Journal of Health and Allied Sciences NU ◽

10.1055/s-0040-1703782 ◽

2014 ◽

Vol 04 (02) ◽

pp. 133-135

Author(s):

Deepthi R. V. ◽

Seema Pavanam ◽

Vijaya Shenoy ◽

Siddarth S. Joshi

Keyword(s):

Autosomal Recessive ◽

Trinucleotide Repeat ◽

Friedreich Ataxia ◽

Autosomal Recessive Disorder ◽

Ataxic Gait ◽

Progressive Ataxia ◽

Extensor Plantar Response ◽

Romberg Test ◽

Endocrine Abnormality ◽

Tendon Reflexes

Abstract:Friedreich ataxia is an autosomal recessive disorder, due to expansion of trinucleotide repeat in Frataxin gene which presents with ataxic gait, absent tendon reflexes, extensor plantar response and positive Romberg test. We present a child who came with complaints of progressive ataxia of gait since the age of 10 years and was diagnosed to have Friedreich ataxia. They have associated cardiomyopathy and endocrine abnormality like diabetes and hypothyroidism.

Download Full-text

Faculty Opinions recommendation of Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1060982.512938 ◽

2007 ◽

Author(s):

Ahmet Hoke

Keyword(s):

Animal Model ◽

Sensory Neuropathy ◽

Peripheral Sensory Neuropathy ◽

Peripheral Sensory

Download Full-text

Clinical Features and Mortality Associated with Severe Malaria in Adults in Southern Mauritania

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6010001 ◽

2020 ◽

Vol 6 (1) ◽

pp. 1

Author(s):

Boushab Mohamed Boushab ◽

Mohamed Salem Ould Ahmedou Salem ◽

Ali Ould Mohamed Salem Boukhary ◽

Philippe Parola ◽

Leonardo Basco

Keyword(s):

Renal Failure ◽

Respiratory Distress ◽

Severe Malaria ◽

Falciparum Malaria ◽

Clinical Features ◽

Signs And Symptoms ◽

Plasmodium Falciparum Malaria ◽

Severe Anaemia ◽

World Health ◽

Health Organization

Severe malaria in adults is not well-studied in Sahelian Africa. Clinical features and mortality associated with severe Plasmodium falciparum malaria in adult patients hospitalized in Kiffa, southern Mauritania, were analysed. Patients over 15 years old admitted for severe malaria between August 2016 and December 2019 were included in the present retrospective study. The World Health Organization (WHO) criteria were used to define severe malaria. The presenting clinical characteristics and outcome were compared. Of 4266 patients hospitalized during the study period, 573 (13.4%) had a positive rapid diagnostic test for malaria, and 99 (17.3%; mean age, 37.5 years; range 15–79 years; sex-ratio M/F, 2.1) satisfied the criteria for severe malaria. On admission, the following signs and symptoms were observed in more than one-fourth of the patients: fever (98%), impairment of consciousness (81.8%), multiple convulsions (70.7%), cardiovascular collapse (61.6%), respiratory distress (43.4%), severe anaemia ≤ 80 g/L (36.4%), haemoglobinuria (27.3%), and renal failure (25.3%). Patients were treated with parenteral quinine or artemether. Fourteen (14.1%) patients died. Multiple convulsions, respiratory distress, severe anaemia, haemoglobinuria, acute renal failure, jaundice, and abnormal bleeding occurred more frequently (p < 0.05) in deceased patients. Mortality due to severe falciparum malaria is high among adults in southern Mauritania. An adoption of the WHO-recommended first-line treatment for severe malaria, such as parenteral artesunate, is required to lower the mortality rate associated with severe malaria.

Download Full-text

Phase II study of an oxaliplatin-based regimen for relapsed colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (INSPIRE study)

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-021-04232-2 ◽

2021 ◽

Author(s):

Keiichiro Ishibashi ◽

Toru Aoyama ◽

Masahito Kotaka ◽

Hironaga Satake ◽

Yasushi Tsuji ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Sensory Neuropathy ◽

Progression Free Survival ◽

First Line ◽

Secondary Endpoints ◽

Grade 3 ◽

Peripheral Sensory ◽

Line Chemotherapy

Abstract Background The aim of this study was to evaluate the efficacy and safety of first-line chemotherapy with re-introduction of oxaliplatin (OX) more than 6 months after adjuvant chemotherapy including OX. Methods Stage II/III colon cancer patients with neuropathies of grade ≤ 1 who relapsed more than 6 months after adjuvant chemotherapy including OX were considered eligible. Eligible patients were treated with 5-fluorouracil, l-leucovorin and OX plus molecularly targeted agents or capecitabine and OX plus bevacizumab (BV) or S-1 and OX plus BV. The primary endpoint was the progression-free survival (PFS), and the secondary endpoints were the overall survival (OS), response rate (RR) and toxicity. Results A total of 50 patients were enrolled between September 2013 and May 2019. Twelve patients received 5-fluorouracil, l-leucovorin and OX (FOLFOX) plus BV, 21 patients received capecitabine and OX plus BV, 10 patients received S-1 and OX plus BV and 7 patients received FOLFOX plus cetuximab or panitumumab. The median PFS was 11.5 months (95% confidence interval [CI] 8.3–16.0), the median OS was 45.4 months (95% CI 37.4–NA), and the RR was 56.0% (95% CI 42.3–68.8). Adverse events of grade ≥ 3 that occurred in ≥ 5% of cases were neutropenia in 6 patients (12%), peripheral sensory neuropathy in 5 patients (10%), diarrhea in 4 patients (8%), hypertension in 4 patients (8%), anorexia in 3 patients (6%) and allergic reactions in 3 patients (6%). Conclusions First-line chemotherapy with re-introduction of OX more than 6 months after adjuvant chemotherapy including OX can be used safely with expected efficacy for relapsed colon cancer patients.

Download Full-text

Siblings with Bardet Beidl Syndrome

Journal of Nepal Paediatric Society ◽

10.3126/jnps.v33i3.8081 ◽

2013 ◽

Vol 33 (3) ◽

pp. 236-238

Author(s):

Ram Peter ◽

Priya Jose ◽

MNG Nair

Keyword(s):

Clinical Features ◽

Autosomal Recessive ◽

Clinical Presentation ◽

The Body ◽

Bardet Biedl Syndrome ◽

Recessive Condition ◽

Autosomal Recessive Condition

Bardet Biedl syndrome is an autosomal recessive condition affecting many parts of the body. Incidence of BBS is 1 in 100000. Its clinical features varies in person to person though from same family too. We are reporting two siblings with Bardet Beidl syndrome with different clinical presentation. DOI: http://dx.doi.org/10.3126/jnps.v33i3.8081 J. Nepal Paediatr. Soc. 2013;33(3):236-238

Download Full-text

Expanding the phenotype of SLC12A6-associated sensorimotor neuropathy

BMJ Case Reports ◽

10.1136/bcr-2021-244641 ◽

2021 ◽

Vol 14 (10) ◽

pp. e244641

Author(s):

Petya Bogdanova-Mihaylova ◽

Patricia McNamara ◽

Sarah Burton-Jones ◽

Sinéad M Murphy

Keyword(s):

Corpus Callosum ◽

Autosomal Recessive ◽

Sensory Neuropathy ◽

Rare Condition ◽

Compound Heterozygous ◽

Sensorimotor Neuropathy ◽

Autosomal Recessive Condition ◽

Solute Carrier ◽

Compound Heterozygous Mutations ◽

Clinical Phenotyping

Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a rare autosomal recessive condition characterised by early-onset severe progressive neuropathy, variable degrees of ACC and cognitive impairment. Mutations in SLC12A6 (solute carrier family 12, member 6) encoding the K+–Cl- transporter KCC3 have been identified as the genetic cause of HMSN/ACC. We describe fraternal twins with compound heterozygous mutations in SLC12A6 and much milder phenotype than usually described. Neither of our patients requires assistance to walk. The female twin is still running and has a normal intellect. Charcot-Marie-Tooth Examination Score 2 was 8/28 in the brother and 5/28 in the sister. Neurophysiology demonstrated a length-dependent sensorimotor neuropathy. MRI brain showed normal corpus callosum. Genetic analysis revealed compound heterozygous mutations in SLC12A6, including a whole gene deletion. These cases expand the clinical and genetic phenotype of this rare condition and highlight the importance of careful clinical phenotyping.

Download Full-text

Frequency and temporal sequence of clinical features in adults with anti-NMDA receptor encephalitis presenting with psychiatric symptoms

Psychological Medicine ◽

10.1017/s0033291718003665 ◽

2018 ◽

Vol 49 (16) ◽

pp. 2709-2716 ◽

Cited By ~ 3

Author(s):

Ronald J. Gurrera

Keyword(s):

Nmda Receptor ◽

Clinical Features ◽

Psychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Signs And Symptoms ◽

Nmda Receptor Encephalitis ◽

Nmdar Encephalitis ◽

Unexplained Fever ◽

Study Inclusion

AbstractBackgroundAnti-NMDA receptor (NMDAr) encephalitis is the most common autoimmune encephalitis in adults. It mimics psychiatric disorders so often that most patients are initially referred to a psychiatrist, and many are misdiagnosed. Without prompt and effective treatment, patients are likely to suffer a protracted course with significant residual disability, or death. This study focuses on the frequency and chronology of salient clinical features in adults with anti-NMDAr encephalitis who are likely to be first evaluated by a psychiatrist because their presentation suggests a primary psychiatric disorder.MethodsA systematic search of PubMed and EMBASE databases identified published reports of anti-NMDAr encephalitis associated with prominent behavioral or psychiatric symptoms. After eliminating redundancies, the frequencies and relative timing of clinical features were tabulated. Signs and symptoms were assigned temporal ranks based on the timing of their first appearance relative to the first appearance of other signs and symptoms in each patient; median ranks were used to compare temporal sequencing of both individual features and major symptom domains.ResultsTwo hundred thirty unique cases (185 female) met study inclusion criteria. The most common features were seizures (60.4%), disorientation/confusion (42.6%), orofacial dyskinesias (39.1%), and mutism/staring (37.4%). Seizures, fever, and cognitive dysfunction were often the earliest features to emerge, but psychiatric features predominated and sequencing varied greatly between individuals.ConclusionsClinicians should consider anti-NMDAr encephalitis when new psychiatric symptoms are accompanied by a recent viral prodrome, seizures or unexplained fever, or when the quality of the psychiatric symptoms is unusual (e.g. non-verbal auditory hallucinations).

Download Full-text

Retrospective analysis of the effect of CAPOX and mFOLFOX6 dose intensity on survival in colorectal patients in the adjuvant setting

Current Oncology ◽

10.3747/co.23.3059 ◽

2016 ◽

Vol 23 (3) ◽

pp. 171 ◽

Cited By ~ 2

Author(s):

A. Mamo ◽

J. Easaw ◽

F. Ibnshamsah ◽

A. Baig ◽

Y.S. Rho ◽

...

Keyword(s):

Colorectal Cancer ◽

Dose Reduction ◽

Real Life ◽

Disease Free Survival ◽

Dose Intensity ◽

Sensory Neuropathy ◽

Stage Iii ◽

Cancer Centre ◽

Peripheral Sensory ◽

Disease Free

Background Despite lack of a true comparative study, the FOLFOX (5-fluorouracil–leucovorin–oxaliplatin) and CAPOX (capecitabine–oxaliplatin) regimens are believed to be similar in their efficacy and tolerability in the treatment of stage III colorectal cancer. However, that belief has been disputed, because real-life data suggest that the CAPOX regimen is more toxic, leading to more frequent reductions in the delivered dose intensity—thus raising questions about the effect of dose intensity on clinical outcomes.Methods A retrospective data review for two Canadian institutions, the Segal Cancer Centre and the Tom Baker Cancer Centre, considered patients diagnosed with stage III colorectal cancer during 2006–2013. Primary endpoints were dose intensity and toxicity, with a secondary endpoint of disease-free survival.Results The study enrolled 180 eligible patients (80 at the Segal Cancer Centre, 100 at the Tom Baker Cancer Centre). Of those 180 patients, 75 received CAPOX, and 105 received mFOLFOX6. In the CAPOX group, a significant dose reduction was identified for capecitabine compared with 5-fluorouracil in mFOLFOX6 group (p = 0.0014). Similarly, a significant dose reduction was observed for oxaliplatin in mFOLFOX6 compared with oxaliplatin in CAPOX (p = 0.0001). Compared with the patients receiving CAPOX, those receiving mFOLFOX6 were twice as likely to experience a treatment delay of more than 1 cycle-length (p = 0.03855). Toxicity was more frequent in patients receiving mFOLFOX6 (nausea: 30% vs. 18%; diarrhea: 47% vs. 24%; peripheral sensory neuropathy: 32% vs. 3%). At a median follow-up of 40 months, preliminary data showed no difference in disease-free survival (p = 0.598). Pooled data from both institutions were also separately analyzed, and no significant differences were found.Conclusions Our results support the use of CAPOX despite a lack of head-to-head randomized trial data.

Download Full-text