Refsum syndrome G60.1

Very rare, autosomal recessive inherited disease in which two forms are distinguished: Infantile form (without skin symptoms - not discussed in detail here): An enzyme deficiency disrupts the breakdown of phytanic acid in the peroxisomes. As a result, phytanic acid and related compounds accumulate in the tissues of the body. The accumulation of phytanic acid is toxic to the cells) and the adult form. The defect in phytanic acid oxidase leads to increased phytanic acid levels in the serum and to phytanic acid deposits in the liver, kidneys, brain and skin.

Clinical picture which clinically belongs to the vulgar ichthyoses with further characteristics (see below ichthyoses).

Described for adult forms are:

• mutations of the PHYH-gene (PAHX-gene), which is mapped on chromosome 10pter-p11.2 and causes a defect of the phytanoyl-CoA hydroxylase
• and
• Mutations of the PEX7 gene (gene locus: 6q22-q24) with consecutive defect of peroxisomal biogenesis factor-7 (peroxin-7).

The enzyme defect leads to an accumulation of phytanic acid, a saturated, branched-chain fatty acid, which is ingested exclusively with food (especially in meat from ruminants). Phytanic acid is not directly metabolized in the healthy organism by mitochondrial or peroxisomal β-oxidation but it is degraded via the so-called peroxisomal alpha-oxidation by the enzyme phytanoyl-CoA hydroxylase.

The defective enzyme is either phytanoyl-CoA hydroxylase itself or peroxin-7, the transport protein responsible for the transport of phytanol-CoA hydroxylase into the peroxisomes.

The result is an accumulation of phytanic acid in the serum and in various tissues, including the nuclei. The result is an accumulation of phytanic acid in serum and in various tissues, including keratinocytes (detection of lipid vacuoles in keratinocytes).

First manifestation in children >10 years); also possible in older adults.

In some patients, clinical picture of (mild) classic vulgar ichthyosis (see ichthyoses below; see also ichthyosis vulgaris, autosomal dominant) with palmoplantar keratoses of varying severity, also ichthyotic erythroderma.

Extracutaneous manifestations: polyneuritis, paresis especially in the distal area of the legs and arms, retinitis pigmentosa, night blindness, papilledema, cerebellar ataxia, anosmia.

Signs of orthhyperkeratosis with reduced or missing Str. granulosum (characteristics of ichthyosis vulgaris). Lipid-containing vacuoles in the keratinocytes.

1. Budden SS et al (1986) Dysmorphic syndrome with phytanic acid oxidase deficiency, abnormal very long chain fatty acids, and pipecolic acidemia: studies in four children. J Pediatr 108: 33-39
2. Choksi V et al (2003) Infantile refsum disease: case report. AJNR Am J Neuroradiol 24: 2082-2084
3. Refsum S, Solomon Islands L, Skatvedt M (1949) Heredopathia atactica polyneuritiformis in children. J Pediat 35: 335-343
4. Sá MJ et al (2015) Infantile Refsum Disease: Influence of Dietary Treatment on Plasma Phytanic Acid Levels. JIMD Rep PubMed PMID: 26303611.