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At a glance

A rare peroxisomal disorder characterized by retinitis pigmentosa, anosmia, peripheral neuropathy, ataxia, bone and skin changes. Cardiomyopathy and arrhythmias may develop later in life.

Synonyms

Phytanic Acid Oxidase Deficiency; Heredopathia Atactica Polyneuritiformis; Hereditary Motor and Sensory Neuropathy IV.

History

The Norwegian neurologist Sigvald B. Refsum (1907-1991) described this syndrome in 1945.

Incidence

Rare. Approximately 1-9/1,000,000 affected individuals.

Genetic inheritance

Autosomal recessive. This slowly progressive disorder is most common in children and young adults of Scandinavian heritage. Age of onset is between 7 months and 50 years of age.

Pathophysiology

Phytanic acid is derived from the metabolism of chlorophyll. Refsum disease (adults form) is caused by mutations in the gene encoding phytanoyl-CoA hydroxylase (PHYH) on 10p13 resulting in accumulation of exogenous phytanic acid (milk, fat of cows and sheep) in blood plasma and tissues. Mutations in PEX7 on 6q23.3 results a peroxisome disorder and leukodystrophy that affects growth of the myelin. This results in the infantile Refsum disease (see below).

Diagnosis

Usually evocated and diagnosed during childhood or young adulthood on the association of retinitis pigmentosa, chronic polyneuropathy, and cerebellar signs. It can be confirmed by laboratory investigations: phytanic acid oxidase deficiency and 3,7,11,15-tetramethyl-hexadecanic acid in serum and tissue deposits. Histological analysis shows interstitial hypertrophic polyneuritis and degeneration of nuclei and fiber tracts in brain stem.

Clinical aspects

Congenital skeletal abnormalities can occur: multiple epiphyseal dysplasia, and bilateral fourth metatarsal shortening. Progressive problems appear secondarily: ocular (retinitis pigmentosa, myosis, ptosis, cataract, nystagmus), neurological (chronic polyneuritis, cerebellar signs, ataxia, anosmia, nerve deafness, hypotonia, hemiparesis), cardiac (electrocardiographic changes, congestive heart failure), and cutaneous (ichthyosis). Other features include renal failure, amyotrophy, and respiratory distress. Dietary treatment avoiding sources of phytanic acid such as dairy, fish, beef, and lamb.

Precautions before anesthesia

A complete evaluation of the cardiac function (echography, ECG, radionuclide imaging if necessary); renal function (kalemia, urea, creatinine); respiratory function (chest radiograph, arterial blood gas analysis, pulmonary function test) must be obtained. A review of the neuropathy evolution and muscular weakness is essential.

Anesthetic considerations

Exacerbation of this disease has been observed with surgery and pregnancy. Perioperative fluid management should be realized in case of renal dysfunction. Careful perioperative positioning is necessary to avoid nerve compression in these patients with neuropathy. Cardiac perioperative monitoring is necessary because of the risk of ECG change.

Pharmacological implications

Avoid cardiodepressive, ototoxic, and nephrotoxic drugs. Aminoglycosides can be used, but real benefit has to be assessed in the presence of incomplete deafness or renal dysfunction. Avoid succinylcholine in patients with neuropathy (risk of hyperkalemia). Local anesthetics are ...

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