OOA (Old Order Amish)

Inheritance: autosomal recessive
Genes: PEX1; PEX2; PEX26

Infantile phytanic storage disease

Hearing deficit
Mental retardation
Failure to thrive
Retinitis pigmentosa
Phytanic acid
Discoloration and irregularity of the teeth
Behavior problems

Infantile Refsum Disease

Clinical Characteristics

General description (for patients):

Symptoms of this disease such as poor muscle tone may be noted at birth.  Development is delayed in all aspects and mental retardation is soon evident.  Hearing is poor as is vision, especially at night.  The liver is enlarged and jaundice may be seen.  Teeth have an orange, yellowish color with large spaces between them.  Once children begin walking they are unsteady and have a wide-based gait.  Behavior/mood problems may become evident after puberty.

Medical description:  

This is a disorder of peroxisomal metabolism with widespread signs and symptoms, many resembling classical Refsum disease.  However, individuals with this form are hypotonic and have global developmental delays from birth.  Retinitis pigmentosa causes night blindness and at least some have optic atrophy with overall poor vision.  Sensorineural hearing deficits are common.  Hepatomegaly with jaundice may lead to the mistaken diagnosis of Byler disease.  Ataxia and motor neuron disease are usually evident early.  The teeth are broad and abnormally shaped with striking yellow-orange discoloration.  Female Amish patients exhibit labile and fearful emotions post-puberty. Diagnosis can be made from elevated plasma levels of phytanic and pipecolic acids, or by demonstration of decreased phytanic acid oxidation in cultured cells.


Infantile Refsum disease is an autosomal recessive disorder due to phytanic oxidase deficiency as a result of mutations in PEX genes 1, 2, and 26.  As yet, the exact gene mutation in the Amish has not been identified and only one family, in Northern Indiana, has been reported.  Loci may be at 8q21.1, 7q21-q22, and 22q11.21


Diets low in phytanic acid have been tried but results are equivocal due to poor adherence.


Unknown. One 9 year old Amish male died of a presumed cardiac arrhythmia.

Ancillary treatments and support:

None known.

Specialists and specialty centers:

Nutritionists, neurologists, pediatricians.


Bader, P.I., Dougherty, S., Cangany, N., Raymond, G., and Jackson, C.E.:  Infantile Refsum disease in four Amish sibs.  Am. J. Med. Genet. 90: 110-114, 2000.  PubMed ID: 10797430

Wanders, R.J., Schutgens, R.B., Schrakamp, G, van den Bosch, H., Tager, J.M., Schram, A.W., Hashimoto, T., Poll-The, B.T., and Saudubrau, J.M.:  Intantile Refsum disease: deficiency of catalases-containing particles (peroxisomes), alkyldihydroxyacetone phosphate synthase and peroxisomal beta-oxidation enzyme proteins.  Eur. J. Pediatr. 145: 172-175, 1986.  PubMed ID: 2429839


Infantile Refsum Disease
NINDS Infantile Refsum Disease Information

Associated Graphics