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At a glance

Mitochondrial disease. NARP is an acronym that stands for Neuropathy, Ataxia, and Retinitis Pigmentosa. Other features include corticospinal tract atrophy, developmental delay, dementia, seizures, cerebellar ataxia, sensory neuropathy, and proximal neurogenic muscle weakness.

Incidence

Unknown. Prevalence is estimated at 1:12,000 populations.

Genetic inheritance

NARP Syndrome is maternally transmitted.

Pathophysiology

NARP Syndrome is caused predominantly by m.8993T>G/C point mutations in the mitochondrial adenosine triphosphate (ATP) synthase subunit 6 gene (MT-ATP6). This MT-ATP6 encodes for subunit 6 of mitochondrial adenosine triphosphatase. Defect of complex V of the respiratory chain enzymes, with progressive loss of mitochondrial bioenergetic capacity. A mutation load or heteroplasmy level (ie, ratio of mutant to wild-type mitochondrial DNA) marks the difference between the phenotypes. Heteroplasmy levels between 70 and 90% lead to NARP Syndrome, but a heteroplasmy level greater than 90% result in ☞Leigh Syndrome (Maternally Inherited Leigh Syndrome [MILS]).

Diagnosis

Clinical and laboratory confirmation of elevated pyruvate and lactate. Muscular biopsy shows ragged-red muscle fibers, and the biochemical defect is often segmental on histochemistry. On ophthalmoscopy, the retina reveals salt-and-pepper retinopathy.

Clinical aspects

Association of neuropathy, ataxia, and retinitis pigmentosa leading progressively to blindness. Other clinical features include mental retardation, progressive deafness, muscle weakness, developmental delay, and sluggish pupils. Onset in young adulthood, with normal development and language problems.

Precautions before anesthesia

Diagnosis of mitochondrial disease should be considered in any child with a multisystem neurologic disorder or who is being investigated for hypotonia. Anesthesia-related morbidity and mortality risk is essentially linked to the preoperative status of the child, that is, the number and extent of organ dysfunction. The presence of a mitochondrial disease is not considered a risk for malignant hyperthermia. Avoid any elective anesthesia/surgery in the presence of infection or temperature because the increase in cytokines (mainly tumor necrosis factor) inhibits some complex of the respiratory chain. The following should be checked: central nervous system (CNS) (seizures, myoclonus, strokes, swallowing problems; usual venous or arterial concentration of lactates and glucose); muscles (hypotonia, contractures, scoliosis); heart (even if the child is asymptomatic, ECG and echocardiography to exclude conduction disorders and cardiomyopathy, respectively; check functioning of pacemaker, if present); respiratory (frequent infections, chronic lung aspiration, pulse oximetry breathing room air should be obtained, obstructive and/or central apnea; reduced ventilatory drive is common, and many patients have an abnormal response to both hypoxia and hypercarbia. Deaths have been reported following sedation with chloral hydrate or diazepam). Other organ involvement includes: hepatic and renal function; nutritional status and diet (glucose and/or lipid rich; tolerance to fasting and treatment [carnitine, vitamin Q, antiepileptic drugs]).

Anesthetic considerations

Usual treatment up to the day of surgery. Preoperative fasting must ...

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