A rare disorder of lipid metabolism characterized by
peripheral neuropathy, ataxia, retinitis pigmentosa, and bone and skin
changes. Other features include cutaneous ichthyosis and cardiac failure.
Phytanic Acid Oxidase Deficiency; Heredopathia Atactica
Polyneuritiformis; Hereditary Motor and Sensory Neuropathy IV.
Autosomal recessive. This slowly progressive
disorder is most common in children and young adults of Scandinavian
Phytanic acid is derived from the metabolism of
chlorophyll. Refsum disease is caused by mutations in the gene encoding
phytanoyl-CoA hydroxylase (PAHX or PHYH) or the gene encoding peroxin-7
(PEX7), resulting in accumulation of exogenous phytanic acid (milk, fat of
cows and sheep) in blood plasma and tissues. It belongs to the pathological
group of leukodystrophy that affects growth of the myelin. Genes are located
on 6q22-q24 and 10pter-p11.2.
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 brainstem.
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.
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.
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.
Avoid cardiodepressive, ototoxic, and
nephrotoxic drugs. Aminoglycosides can be used, but real interest has to be
evaluated in the presence of incomplete deafness or renal dysfunction. Avoid
succinylcholine in patients with neuropathy (risk of hyperkalemia). Local
anesthetics are not contraindicated; however, the interest should be evaluated in
consideration for an evolutive neuropathic disease. Clear
information has to be given and understood by the patient.
Refsum Infantile Form (Infantile Phytanic Acid Storage
Disease): Autosomal recessive. Caused by mutations in peroxisomal membrane
protein-3 (35 kDa); gene located on 8q21.1, 7q21-q22. Clinical features
include early onset, mental retardation, minor facial dysmorphism, retinitis
pigmentosa, sensorineural hearing deficit, hepatomegaly, osteoporosis,
failure to thrive, and hypocholesterolemia.
Refsum Disease with Increased Pipecolic Acidemia (RDPA): Autosomal recessive. Gene located on 10pter-p11.2. Characterized by
accumulation of l-pipecolic acid and clinically by rapidly progressing