Polyuria and Acute Hyperglycemia Secondary to New-Onset Diabetes in a Young Woman With Friedreich’s Ataxia

Santos J, Woloski J R, Wu N (June 29, 2021); Cureus 13(6): e16032. doi:10.7759/cureus.16032 

Diabetes is a common complication in patients with FRDA and should be routinely screened for by healthcare providers, preferably via an OGTT. Treatment of diabetes can be challenging due to neurodegenerative symptoms that may interfere with the ability to self-administer insulin. Additionally, close follow-up with cardiology is important to monitor for any signs or symptoms of cardiomyopathy, especially after the initiation of diabetes medications. Once diabetes is diagnosed, an individualized treatment plan along with efficient coordination of care is essential for successful diabetes management in patients with FRDA.

Cardiac Involvement in Movement Disorders

Rossi M, Wainsztein N, Merello M.; Mov Disord Clin Pract. 2021 Apr 7;8(5):651-668. doi: 10.1002/mdc3.13188. PMID: 34307738; PMCID: PMC8287161.

As cardiac disease is part of the phenotypic spectrum of several movement disorders, heart involvement should be carefully investigated and increased awareness of this association encouraged as it may represent a leading cause of morbidity and mortality.

Neuro-Ophthalmological Findings in Friedreich’s Ataxia

Rojas, P.; de Hoz, R.; Cadena, M.; Salobrar-García, E.; Fernández-Albarral, J.A.; López-Cuenca, I.; Elvira-Hurtado, L.; Urcelay-Segura, J.L.; Salazar, J.J.; Ramírez, J.M.; Ramírez, A.I.; J. Pers. Med. 2021, 11, 708. doi:10.3390/jpm11080708 

Although most patients with FRDA do not present with symptomatic visual impairment, 73% present with clinical neuro-ophthalmological alterations such as optic atrophy and altered eye movement, among others. This review provides a brief overview of the main aspects of FRDA and then focuses on the ocular involvement of this pathology and the possible use of retinal biomarkers.

Very late-onset Friedreich’s ataxia with rapid course mimicking as possible multiple system atrophy cerebellar type

Tushar Ashok Vidhale, Hemant R Gupta, Rohan PJ and Charmi Gandhi; BMJ Case Reports CP 2021;14:e242073, doi:10.1136/bcr-2021-242073 

This 55-year-old man was admitted to the hospital with an insidious onset, progressive backward fall (due to severe truncal ataxia), dysarthria, stiffness in extremities, distal dominant muscle wasting along with behavioural changes and urinary incontinence. Clinical assessment indicated mild cognitive decline (Mini-Mental State Examination 22/27) with cerebellar, pyramidal and peripheral nerves involvement. On investigations, nerve conduction studies revealed symmetrical, sensorimotor peripheral neuropathy affecting both lower limbs. Brain and whole spine MRI revealed widespread cerebral and mild cerebellar atrophy, pons and medulla volume loss, and a normal spinal cord. Transthoracic echocardiography revealed concentric left ventricular hypertrophy. His gene analysis revealed eight GAA repeats on allele 1, and 37 GAA repeats on allele 2 in the first intron of the frataxin gene. Considering his clinical profile and genetic analysis, he was diagnosed as a case of very late-onset Friedreich’s ataxia with likely compound heterozygous genotype.

A Study to Assess Efficacy, Long Term Safety and Tolerability of RT001 in Subjects With Friedreich's Ataxia

UCLA Health, NCT No. NCT04102501; Phase 3 

 The purpose of this study is to assess the Efficacy, Long Term Safety and Tolerability of RT001 in subjects with Friedreich's Ataxia 

 Open Actively Recruiting

Rare occurrence of severe blindness and deafness in Friedreich ataxia: a case report

Joana Damásio, Ana Sardoeira, Maria Araújo, Isabel Carvalho, Jorge Sequeiros & José Barros; Cerebellum & Ataxias volume 8, Article number: 17 (2021) doi:10.1186/s40673-021-00140-6 

With this report we wish to further contribute to the characterization of optic and auditory involvement in FRDA, stress the need to better understand the underlying mechanisms, as well as their genetic and epigenetic modifying factors (including somatic heterogeneity); and increase awareness for this rare extreme phenotype. Improved healthcare services and longer survival of early-onset patients will probably increase the frequency of these devastating manifestations.

Gene therapies and COVID-19 vaccines: a necessary discussion in relation with viral vector-based approaches

Angel Aledo-Serrano, Antonio Gil-Nagel, Julian Isla, Ana Mingorance, Fernando Mendez-Hermida & Ruben Hernandez-Alcoceba; Orphanet J Rare Dis 16, 316 (2021). doi:10.1186/s13023-021-01958-3 

 In conclusion, the potential interference between gene therapy and virus-based vaccines deserves a careful consideration and discussion involving the patient community. This is a adequate moment to do so, since current vaccine candidates are not expected to cause such interference. Should people with monogenic diseases preferentially receive, or be given the option to be immunized COVID-19 vaccines based on non-viral platforms, such as the mRNA vaccines? A careful consideration of the impact on the use of vectors for vaccine production and the plausible negative impact in the development of suitable gene therapy medicinal products, should be on top of the scientific and regulatory table discussion in order to facilitate access to patients suffering monogenic diseases and also prevent unnecessary delays in future vector vaccines development.

Myocardial Perfusion Reserve in Children with Friedreich Ataxia

Hutchens JA, Johnson TR, Payne RM.; Pediatric Cardiology. 2021 Jul. DOI: 10.1007/s00246-021-02675-1. 

This retrospective study shows that children with FA develop MPR defects early in the disease process. It also suggests MPR may be a sensitive tool to evaluate underlying cardiac compromise and could be of use in directing surgical management decisions in children with FA.

Interruptions of the FXN GAA Repeat Tract Delay the Age at Onset of Friedreich’s Ataxia in a Location Dependent Manner

Nethisinghe, S.; Kesavan, M.; Ging, H.; Labrum, R.; Polke, J.M.; Islam, S.; Garcia-Moreno, H.; Callaghan, M.F.; Cavalcanti, F.; Pook, M.A.; Giunti, P. Int. J. Mol. Sci. 2021, 22, 7507. doi:10.3390/ijms22147507 

The GAA repeat tract in some cases may be impure with sequence variations called interruptions. It has previously been observed that large interruptions of the GAA repeat tract, determined by abnormal MboII digestion, are very rare. Here we have used triplet repeat primed PCR (TP PCR) assays to identify small interruptions at the 5′ and 3′ ends of the GAA repeat tract through alterations in the electropherogram trace signal. We found that contrary to large interruptions, small interruptions are more common, with 3′ interruptions being most frequent. Based on detection of interruptions by TP PCR assay, the patient cohort (n = 101) was stratified into four groups: 5′ interruption, 3′ interruption, both 5′ and 3′ interruptions or lacking interruption. Those patients with 3′ interruptions were associated with shorter GAA1 repeat tracts and later ages at disease onset. The age at disease onset was modelled by a group-specific exponential decay model. Based on this modelling, a 3′ interruption is predicted to delay disease onset by approximately 9 years relative to those lacking 5′ and 3′ interruptions. This highlights the key role of interruptions at the 3′ end of the GAA repeat tract in modulating the disease phenotype and its impact on prognosis for the patient.

Would Francisco Soca have been the first to relate toe phenomenon as pyramidal disorders?

élio A.G. Teive, Carlos Henrique F. Camargo, Nicolás Sommaruga, Héctor Ignacio Amorin-Costábile, Olivier Walusinski; Journal of Clinical Neuroscience, Volume 91, 2021, Pages 172-175, doi:10.1016/j.jocn.2021.07.013. 

 The Uruguayan physician Francisco Soca, who specialized in neurology in Jean-Martin Charcot’s clinic, defended a thesis at the Paris Faculty of Medicine in 1888 on Friedreich's ataxia in eleven patients. In this work he described the presence of toe phenomenon. In the late 1800s Soca completed a specialization in neurology at the service run by Charcot in Paris. He defended an important thesis in 1888 assessing data from 11 Friedreich’s ataxia. In his thesis, Soca also described the toe phenomenon and the presence of structural changes in the feet of these patients that were not described in the Friedreich study published in 1863. The Soca’s thesis contained the description of toe extension associated with pyramidal tract lesions, eight years later described and further immortalized as Babiński's sign. Therefore, Soca had already publicized this sign as being representative of a pyramidal dysfunction before Babiński or any other neurologist.