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Friedreich Ataxia (FA)

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Comorbidities

Friedreich ataxia (FA) is a rare hereditary ataxia, typically seen in children and young adults, that is characterized by gait and limb ataxia, dysarthria, and loss of lower limb reflexes. FA also tends to present with comorbidities, including ulcerative colitis, Crohn’s disease, inflammatory bowel disease, and obstructive sleep apnea. Some patients may also experience emotional and psychological symptoms, such as anxiety and depression. Some of these conditions may be evident at diagnosis, while some may develop as the patient’s FA progresses. 1

Gastrointestinal Disorders

A 2016 retrospective study reviewed medical information from a large multicenter natural history trial of 641 patients with FA (FACOMS cohort) to investigate comorbid medical conditions.2 

The study found a higher prevalence of comorbid ulcerative colitis, Crohn’s disease, and inflammatory bowel disease (or IBD characterized by the presence of both Crohn disease and ulcerative colitis) in the FA cohort than in the general population. Of the 641 subjects, 3 had ulcerative colitis, 3 had Crohn disease, and 10 had IBD. Thus, within the FA cohort, the respective prevalence rates of ulcerative colitis, Crohn disease, and IBD were 2, 2.5, and 3.5 times the rates of the general population. In this study, the onset of gastrointestinal problems occurred on average 8.6 ± 5.3 years after the onset of neurological symptoms. The most common symptom of IBD in FA was diarrhea.2

In addition, 4 patients with FA were deficient in human growth hormone (hGH). Thus, the prevalence of hGH deficiency in the FA cohort was 28 times that of individuals without FA. The study also found that hGH deficiency was not linked to the length of the guanine-adenine-adenine (GAA) trinucleotide repeat. Clinical studies showed expanded GAA trinucleotide repeats on both alleles of the FXN gene in 96% of patients with FA. The remaining patients have an expanded GAA repeat on one allele and large deletion or point mutation on the other.2

Read more about FA genetics

Mental Health Issues

Several studies have reported emotional and psychological symptoms, such as anxiety and depression, in patients with FA. 

A descriptive observational study of 57 patients with FA found that the severity and prevalence of depressive symptoms (sadness, loss of pleasure, pessimism, punishment feelings, suicidal thoughts, agitation, worthlessness, loss of energy, irritability, and fatigue) were higher in patients with FA than in the general population.2,3

A longitudinal study of cognitive function in 29 patients with FA conducted during a period of 8.24 years demonstrated a significant decline over time in several cognitive domains, including verbal fluency, processing speed, and visuoconstructive skills.4

A meta-analysis of 18 neuropsychological studies from 1950 to 2021 confirmed that patients with FA perform significantly worse than the general population in the cognitive domains of attention, executive function, language, memory, visuospatial function, emotion recognition, and social cognitive abilities. The cognitive impairments in the study were found to be linked to changes in the cerebellar structure.5

In a 10-year observational study, from 2010 to 2020, of a cohort of 175 patients with FA, the incidence of comorbidities varied according to duration of disease, with a higher number of psychotic symptoms (hallucinations or delusions) observed in patients with a very long duration of disease than in the general population.6

Read more about FA prognosis

Respiratory Dysfunction

A retrospective observational study of respiratory data collected across 3 years (from 2018 to 2021) from 44 patients with FA found a recurrent restrictive pattern of respiratory dysfunction in this cohort. Reductions in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and peak expiratory flow (PEF) were noted; the expiratory function was the most compromised.7

A study by Corben et al found a higher prevalence (21%) of obstructive sleep apnea (OSA) syndrome in an FA cohort than in the general population. The OSA was often associated with hypoxia (oxygen desaturation index >5/h). The authors suggested that OSA may be caused by upper airway collapse due to deficits in pharyngeal muscle activity.8

Read more about FA risk factors

Sexual Dysfunction

A study of 179 adult patients confirmed a comorbidity of sexual dysfunction in patients with FA. Erectile dysfunction was reported in 57% of male patients, insufficient vaginal lubrication in 57.7% of female patients, and reduced genital sensation in 47% of patients.9

Read more about FA treatment

References

  1. Cook A, Giunti P. Friedreich’s ataxia: clinical features, pathogenesis and management. Br Med Bull. 2017;124(1):19-30. doi:10.1093/bmb/ldx034
  2. Shinnick JE, Schadt K, Strawser C, et al. Comorbid medical conditions in Friedreich Ataxia: association with inflammatory bowel disease and growth hormone deficiency. J Child Neurol. 2016;31(9):1161-1165. doi:10.1177/0883073816643408
  3. Nieto A, Hernández-Torres A, Pérez-Flores J, Montón F. Depressive symptoms in Friedreich ataxia. Int J Clin Health Psychol. 2018;18(1):18-26. doi:10.1016/j.ijchp.2017.11.004
  4. Hernández-Torres A, Montón F, Hess Medler S, de Nóbrega É, Nieto A. Longitudinal study of cognitive functioning in Friedreich’s ataxia. J Int Neuropsychol Soc. 2021;27(4):343-350. doi:10.1017/S1355617720000958
  5. Naeije G, Schulz JB, Corben LA. The cognitive profile of Friedreich ataxia: a systematic review and meta-analysis. BMC Neurol. 2022;22(1):97. doi:10.1186/s12883-022-02615-3
  6. Fichera M, Castaldo A, Mongelli A, et al. Comorbidities in Friedreich ataxia: incidence and manifestations from early to advanced disease stages. Neurol Sci. 2022;43(12):6831-6838. doi:10.1007/s10072-022-06360-w
  7. Vinante E, Colombo E, Paparella G, Martinuzzi M, Martinuzzi A. Respiratory function in Friedreich’s ataxia. Children (Basel). 2022;9(9):1319. doi:10.3390/children9091319
  8. Corben LA, Ho M, Copland J, Tai G, Delatycki MB. Increased prevalence of sleep-disordered breathing in Friedreich ataxia. Neurology. 2013;81(1):46-51. doi:10.1212/WNL.0b013e318297ef18
  9. Corben LA, Hermans MM, Marks A, Crowe LM, Delatycki MB. Sexual function, intimate relationships and Friedreich ataxia. J Neurol. 2021;268(3):1088-1095. doi:10.1007/s00415-020-10258-y

Reviewed by Debjyoti Talukdar, MD, on 1/28/2023.

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