The mitochondrial protein frataxin plays a central role in mitochondrial iron homeostasis, and frataxin deficiency is responsible for Friedreich ataxia, a neurodegenerative and cardiac disease that affects 1 in 40000 children. Here we present a single-particle reconstruction from cryoelectron microscopic images of iron-loaded 24-subunit oligomeric frataxin particles at 13 and 17 Å resolution. Computer-aided classification of particle images showed heterogeneity in particle size, which was hypothesized to result from gradual accumulation of iron within the core structure. Thus, two reconstructions were created from two classes of particles with iron cores of different sizes. The reconstructions show the iron core of frataxin for the first time.

Read More: Structural basis of the iron storage function of frataxin from single-particle reconstruction ...

Our aim was to evaluate with modern tools the efficacy of orthopedic shoes on gait disorders in Friedreich's ataxia. The case of a 26-year-old woman with Friedreich's ataxia is described. She mainly complained of fatigability, ankle instability, frequent falls and pain. Impairments involved a cerebellar syndrome, a proprioceptive deficit, an upper motor neurone syndrome and osteoarticular deformities. Gait disabilities included ataxia and requirement of a cane. Handicap concerned outings, altering quality of life. Orthopedic shoes combined with physical therapy were prescribed. Assessment of treatment was planned after one month. Self-assessment by the patient was noted. Clinical assessment was provided by physical examination and clinical gait analysis supported by video. Quantified assessment was performed with a Gaitrite system recording spatiotemporal gait parameters.

Read More: Orthopedic shoes improve gait in Friedreich's ataxia: a clinical and quantified case study

PURPOSE:
Friedreich's ataxia is a genetically transmitted, progressive spinocerebellar degenerative disease characterized by ataxia. The purpose of this study is to evaluate the demographics, progression, nonoperative, and operative treatment of spinal deformities in patients with Friedreich's ataxia at 2 tertiary pediatric orthopaedic hospitals.

METHODS:
After institutional review board approval, chart review of Friedreich's ataxia patients identified those having scoliosis. Demographic data, length of follow-up, brace treatment, operative treatment, and complications were determined. Radiographic review was also performed.

RESULTS:
Seventy-seven patients were identified as having Friedreich's ataxia, of which 49 (63%) were diagnosed with scoliosis. Twenty-seven were male; 22 were female.

Read More: Friedreich's ataxia and scoliosis: the experience at two institutions

Marked rearrangement of energy metabolism, a response to cellular stress and altered expression of proteins involved in cell structure, motility and metabolism.

A frequent cause of death in Friedreich's ataxia patients is cardiomyopathy, but the molecular alterations underlying this condition are unknown. We performed 2-DE to characterize the changes in protein expression of hearts using the muscle creatine kinase frataxin conditional knockout (KO) mouse. Pronounced changes in protein expression profile were observed in 9 week-old KO mice with severe cardiomyopathy. In contrast, only several proteins showed altered expression in asymptomatic 4 week-old KO mice. In hearts from frataxin KO mice, components of the iron-dependent complex-I and -II of the mitochondrial electron transport chain and enzymes involved in ATP homeostasis (creatine kinase, adenylate kinase) displayed decreased expression. Interestingly, the KO hearts exhibited increased expression of enzymes involved in the citric acid cycle, catabolism of branched-chain amino acids, ketone body utilization and pyruvate decarboxylation.

Read More: Proteomic analysis of hearts from frataxin knockout mice