Refsum dieetistä nykyistä tiedettä , aivan päivitettyä 2026

 

Diagnosis and Metabolic Management of Adult Refsum Disease: Guidance From the Medical and Scientific Committee of Global DARE (Defeat Adult Refsum Everywhere).

Ramachandran R, Buttigieg R, Eichler F, Leroy BP, Mahroo O, Huckfeldt RM, Firman S, Baldwin E, DeMarco K, Kuranoff S, Fine A, Klingel R, Ferdinandusse S, Hacia JG, Wanders RJ, Wierzbicki AS.J Inherit Metab Dis. 2026 May;49(3):e70201. doi: 10.1002/jimd.70201.PMID: 42161578 Free PMC article. Review.

Adult Refsum disease (ARD; OMIM 266510) is a degenerative autosomal recessive condition typically diagnosed in adulthood. ...Greater clinician and patient awareness will lead to early diagnosis and improved outcomes. Implementation of a low PA diet before further en …

2

Adult Refsum Disease: Case Series of Reducing Circulating Phytanic Acid Levels With Dietary Interventions.

Firman SJ, Cook J, Hall I, Yeung K, Buttigieg R, Vaz F, Wierzbicki AS, Ramachandran R.JIMD Rep. 2026 May 15;67(3):e70048. doi: 10.1002/jmd2.70048. eCollection 2026 May.PMID: 42145913 Free PMC article.

Adult Refsum disease (ARD, OMIM #266510) is an autosomal recessive condition, resulting in phytanic acid (PA) accumulation in plasma and tissue. ...Four patients already established on the low PA diet for > 10 years experienced a rapid rise in circulating PA levels due to weight loss and/or inadequate carbohydrate intakes, despite adherence to a low PA diet. Circulating PA levels more than doubled in all four of these cases. Implementing dietary interventions to ensure adequate energy, carbohydrates and weight stabilisation resulted in a decrease in circulating PA levels by 47%-84% in the outpatient setting. The reduction in circulating PA occurred within 1.6-5 months. These cases demonstrate that PA restriction, and weight and carbohydrate management have integral roles in ensuring metabolic stability in ARD. This case series highlights that circulating PA levels can be reduced more rapidly with dietary interventions than previously shown in case series of chronic management.

3

 

Synthesis of stable isotope labeled analogs of phytanic acid for separate and combined tracing of alpha-, beta- and omega-oxidation.

Broadrup RL, Schwartz AC, Smith J, von Trentini D, Snyder NW.bioRxiv [Preprint]. 2025 Nov 27:2025.11.24.689497. doi: 10.1101/2025.11.24.689497.PMID: 41394623 Free PMC article. Preprint.

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched very long chain fatty acid (VLCFA) derived in humans from the diet and catabolized via peroxisomal metabolism. Catabolism of phytanic acid is important in humans as certain inborn errors of peroxisomal me …

4

Identification of novel pathogenic variants in the PHYH gene and extending the phenotypic range in Refsum disease.

Gregory-Evans CY, Lehman A, Mattman A, Kirby M, Gregory-Evans K.Ophthalmic Genet. 2026 Jun;47(3):283-286. doi: 10.1080/13816810.2025.2591819. Epub 2025 Nov 25.PMID: 41290216

Both patients were referred to the metabolic disease clinic and phytanic acid levels were found to be 256 g/mL in P1 (normal is < 3 g/mL) and 48.2 mol/L in P2 (normal is < 2.2 mol/L) confirming the diagnosis of Refsum disease. Both patients shared systemic featur

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5

 

Forty-year odyssey to Refsum disease diagnosis: impact of diagnostic delay on effective treatment.

Truong P, Mack HG, Metha AB, Deen N, Hickey DG, Huq A, Britten-Jones AC, Ayton LN.Clin Exp Optom. 2025 Jul;108(5):636-639. doi: 10.1080/08164622.2024.2401509. Epub 2024 Sep 15.PMID: 39277904 Free article. No abstract available

Keywords: Diet; multidisciplinary care; retinitis pigmentosa; syndrome.

KOMMENTTIA fytaanihappoa vähentävästä dieetistä: Koska fytaanihappo on pitkä haaralnen rasvahappo,  jossa  sivuhaarat sijaitsevat strategisessa  a.-hiili asemassa  siten että tavallinen beta-oksidaatio ei voi alkaa ilman siihen spesifioitunutta entsyymiä,  tämän hapon liikkertymä haijastaa ongelmaa juuri tuossa entsyymikohdassa. Tuon kohdan pitää lisäksi olla  stereoisomeerisesti oikein päin, jotta entsyymi  pystyyn. Normlaaisti  fytaanihaposta pitäisi tulla pristaanihappoa, joka jatkaa  betaoksidaatiotietä. siitä tiestä   saadaan mm. koliinia normaalisti, joten koliini ei ole vitamiini, vaikka jotkut sitä  vitamiiniksi  ajattelisivat. 

Jo Raamatun ohjeet kyllä antaisivat   Refsumin dieettiin viittavat ohjeita, jos huomattaisiin . Nimittäin  fytaanihappo on mm. naudan rasvaosassa, myös rasvaisissa  kaloissa,   rasvaisissa maitotuotteissa. Myös  kasvikunnassa  kuoriosassa  pähkinöitä.  kuten maapähkinän kuoressa.  Mooseksen laissa  käskettiin rasvaosat erottaa  Jumalalle itselleen  niistä lihauhreista, joita papisto söi.  (Luoja halusi  säästää pappien sydämet ja silmät hyvässä kunnossa) ,Osista hedelmiä mainittiin ettei kuorta tulisi käyttää. Paavali mainitsi että maitosopii lapsille, ja aikuisille kuuluu täysikäisen ruoka.  Nämä esimerkit ainakin huomaan. Nykyaika antaa hyvin tarkat  dieettiohjeet. 

Tauti on harvinainen ja  silmäoireitten ilmetessä  dieetti  on tärkeä.Laboratoriossa   on mitattavissa  fytaanihappopitoisuudet. 

https://www.defeatadultrefsumeverywhere.org/diet-guide

Beta-oksidation, alfa-oksidation ja isopreenirakenteet . AMACR geeni , alfa-metyyli-Coa Rasemaasi, koliininmuodostuksessa tärkeä kohta

 https://pubmed.ncbi.nlm.nih.gov/11893780/

. 2002 Mar;43(3):438-44.

Stereochemistry of the peroxisomal branched-chain fatty acid alpha- and beta-oxidation systems in patients suffering from different peroxisomal disorders

S Ferdinandusse 1, H Rusch, A E M van Lint, G Dacremont, R J A Wanders, P Vreken

Affiliations

• PMID: 11893780

Free articleAbstract

Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is a branched-chain fatty acid derived from dietary sources and broken down in the peroxisome to pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) via alpha-oxidation. Pristanic acid then undergoes beta-oxidation in peroxisomes. Phytanic acid naturally occurs as a mixture of (3S,7R,11R)- and (3R,7R,11R)-diastereomers. In contrast to the alpha-oxidation system, peroxisomal beta-oxidation is stereospecific and only accepts (2S)-isomers. Therefore, a racemase called alpha-methylacyl-CoA racemase is required to convert (2R)-pristanic acid into its (2S)-isomer. To further investigate the stereochemistry of the peroxisomal oxidation systems and their substrates, we have developed a method using gas-liquid chromatography-mass spectrometry to analyze the isomers of phytanic, pristanic, and trimethylundecanoic acid in plasma from patients with various peroxisomal fatty acid oxidation defects. In this study, we show that in plasma of patients with a peroxisomal beta-oxidation deficiency, the relative amounts of the two diastereomers of pristanic acid are almost equal, whereas in patients with a defect of alpha-methylacyl-CoA racemase, (2R)-pristanic acid is the predominant isomer. Furthermore, we show that in alpha-methylacyl-CoA racemase deficiency, not only pristanic acid accumulates, but also one of the metabolites of pristanic acid, 2610-trimethylundecanoic acid, providing direct in vivo evidence for the requirement of this racemase for the complete degradation of pristanic acid.

• https://www.sciencedirect.com/science/article/abs/pii/S1096719217302378?via%3Dihub

https://www.genecards.org/search/results?q=alpha-methylacyl-CoA+racemase%2c

GeneCards Summary(1 record)

• GeneCards: AMACR encodes alpha-methylacyl-CoA racemase, an enzyme that converts pristanoyl-CoA and C27-bile acyl-CoAs between their (R)- and (S)-stereoisomers. This reaction is required for degradation of these substrates by peroxisomal beta-oxidation. The protein functions in metabolic pathways linked to bile acid biosynthesis and fatty acid metabolism. The encoded enzyme localizes to the mitochondrion, peroxisome, cytoplasm, and plasma membrane, placing it at the center of intracellular lipid handling. Its activity is associated with catalytic function and binding, and tissue expression is high in the respiratory system and renal system, with substantial expression in the hepatobiliary system and proximal digestive tract. Read-through transcription also exists between AMACR and the upstream neighboring C1QTNF3 gene. Pathogenic variants in AMACR are reported in congenital bile acid synthesis defect type 4 and alpha-methylacyl-CoA racemase deficiency. Mutations in AMACR have also been associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis.
• Alias: Alpha-Methylacyl-CoA Racemase
• Alias: 2-Methylacyl-CoA Racemase
• NCBI Gene: This gene encodes a racemase. The encoded enzyme interconverts pristanoyl-CoA and C27-bile acylCoAs between their (R)- and (S)-stereoisomers. The conversion to the (S)-stereoisomers is necessary for degradation of these substrates by peroxisomal beta-oxidation. Encoded proteins from this locus localize to both mitochondria and peroxisomes. Mutations in this gene may be associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the upstream neighboring C1QTNF3 (C1q and tumor necrosis factor related protein 3) gene. [provided by RefSeq, Mar 2011]
• Molecular Function(3 records)
  • alpha-methylacyl-CoA racemase,expressed in liver,peroxisomal,converting pristanoyl-CoA and C27 beta acyl-CoA to their (5) stereoisomers,essential step for the formation of cholic acid by the normal peroxisomal pathway (GENATLAS)
  • Acts only on coenzyme A thioesters, not on free fatty acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis), and arylpropionic acids like the anti-inflammatory drug ibuprofen (2-(4-isobutylphenyl)propionic acid) but neither 3-methyl-branched nor linear-chain acyl-CoAs. (UniProtKB/TrEMBL)
  • Disorder(2 records)
    • Alpha-Methylacyl-Coa Racemase Deficiency Gene-disease relationship from OMIM®, UniProtKB/Swiss-Prot, ClinVar and three more
      Aliases:

      Alpha-Methylacyl-Coa Racemase Deficiency
      Symptoms:

      reduced alpha-methylacyl-coa racemase activity in cultured fibroblasts
      Summaries:

      • Alpha-methylacyl-CoA racemase (AMACR) deficiency is a disorder that causes a variety of neurological problems that begin in adulthood and slowly get worse. People with AMACR deficiency may have a gradual loss in intellectual functioning (cognitive decline), seizures, and migraines. They may also have acute episodes of brain dysfunction (encephalopathy) similar to stroke, involving altered consciousness and areas of damage (lesions) in the brain. Other features of AMACR deficiency may include weakness and loss of sensation in the limbs due to nerve damage (sensorimotor neuropathy), muscle stiffness (spasticity), and difficulty coordinating movements (ataxia). Vision problems caused by deterioration of the light-sensitive layer at the back of the eye (the retina) can also occur in this disorder.
    • Bile Acid Synthesis Defect, Congenital, 4 Gene-disease relationship from OMIM®, UniProtKB/Swiss-Prot, ClinVar and two more
      Aliases:

      • 2-Methylacyl-Coa Racemase Deficiency
      • Alpha-Methyl-Acyl-Coa Racemase Deficiency
      • Alpha-Methylacyl-Coa Racemase Deficiency