[MIM 229 300, 601 992]

(Spino-cerebellar ataxia)

It is the most common  hereditary spino-cerebellar ataxia: prevalence: 1/29,000.

Neurodegenerative disease. Autosomal recessive transmission.

In 98 % of cases: exaggerated expansion of the GAA triplet (> 70, normal: 5-30) at the level of the FXN gene coding for frataxine (9q21.11). In the  other cases, there is a mutation or a deletion of the same gene. The disease occurs if the two parental alleles are affected: patients are homozygous or compound heterozygous (a different mutation on each allele).

The mutation of the frataxin gene causes intra-mitochondrial iron accumulation that causes cell death (spinocerebellar and spinocortical tracts, cardiomyocytes): it is therefore a form of mitochondrial disease.

Clinical onset between the age of 7 and 14 years (before 20 years in 80 % of cases):

-        ataxia: due to the combination of cerebellar, sensory and vestibular anomalies

-        axonal neuropathy: loss of tendon reflexes of the lower limbs with plantar reflex in extension. Some forms are characterized by a later loss of tendon reflexes

-        neuropathy: loss of proprioception and vibratory sensation

-        dysarthia often associated with dysphagia (risk of aspiration)

-         hollow feet

-         hypertrophic cardiomyopathy of the left ventricule (85 %) (increased number of mitochondria but loss of contractile fibres) which becomes dilated at the end of evolution: cardiac failure and / or atrial arrhythmias are common; palpitations, syncopes, precordial pain. Sometimes the cardiac symptoms appear before the neurologic signs

-        neuromuscular scoliosis (> 50%)

-         visual (optic neuropathy) and hearing disorders

-         diabetes mellitus due to insulin resistance

-        risk of death of cardiac origin (failure, rhythm disorders); some patients can benefit from cardiac transplantation

Treatment: medical, multidisciplinary management. Oral administration of omaveoxolone appears to slow the progression (side-effects: increased transaminases, headache, diarrhea).

Anesthetic implications: 

NO succinylcholine : posssible risk of hyperkalemia. Risk of aspiration pneumonia. Preoperative echocardiography and ECG. Monitor blood glucose levels. Avoid low blood pressure because the cardiac ventricular wall is enlarged, resulting in a risk of coronary ischemia. Occasionally, children are equiped with an internal automatic defibrillator.

In case of scoliosis, intraoperative transoesophageal cardiac ultrasound should be used. Baseline neuromuscular evoked potentials are inadequate in > 20 % of cases, necessitating an intraoperative awakening procedure to check the integrity of motor functions after placement of the spinal equipment. Total IV anaesthesia with propofol has been used without problems in a large number of cases.

References : 

-         Schmitt HJ, Wick S, Münster T. 
Rocuronium for muscle relaxation in two children with Friedreich's ataxia. 
Br J Anaesth 2004; 92: 592-6.

-         Pancaro C, Renz D. 
Anesthetic management in Friedreich’s ataxia. 
Pediatr Anesth 2005; 15: 433-4.

-         Wyatt S, Brighouse D. 
Anaesthetic management of vaginal delivery in a woman with Friedreich’s ataxia complicated by cardiomyopathy and scoliosis. 
Int J Obstetr Anaesth 1998; 7: 185-8.

-         Delatycki MB, Corben LA. 
Clinical features of Friedreich ataxia. 
J Child Neurol 2012 ; 27 : 1133-7.

-         Payne RM, Wagner GR. 
Cardiomyopathy in Friedreich ataxia : clinical findings and research. 
J Child Neurol 2012 ; 27 : 1179-1186.

-         Huercio I, Guasch E, Brogly N, Gilsanz F. 
Anaesthesia for orphan disease: Combined spinal-epidural anaesthesia in a patient with Friedreich’s ataxia. 
Eur J Anaesthesiol 2014 ; 31 : 340-1. 

-        Norrish G, Rance T, Montanes E, Field E, Brown E et al.
Friedreich’s ataxia-associated hypertrophic cardiomyopathy : a national cohort study.
Arch Dis Child 2022 ; 107 :450-5.

-        Corben LA , Collins V, Milne S, Farmer J, Musheno A,  Lynch D, Subramony S, Pandolfo M, Schulz JB, Lin K , Delatycki MB on behalf of the Clinical Management Guidelines Writing Group.
Clinical management guidelines for Friedreich ataxia: best practice in rare diseases.
Orphanet Journal of Rare Diseases (2022) 17:415.

-        O’Brien EM, Neiswinter N, Lin KY, et al.
Perioperative management and outcomes for posterior spinal fusion in patients with Friedreich ataxia: A single-center, retrospective study.
Pediatr Anesth. 2024;34:654-61.

Updated: June 2024