The Challenges of a Successful Pregnancy in a Patient with Adult Refsum’s Disease due to Phytanoyl-CoA Hydroxylase Deficiency

  • Karolina M. Stepien
  • Anthony S. Wierzbicki
  • Bwee T. Poll-The
  • Hans R. Waterham
  • Christian J. Hendriksz
Case Report
Part of the JIMD Reports book series (JIMD, volume 33)


We describe the management and outcomes of pregnancy in a 27-year-old woman with infantile-onset Adult Refsum’s disease (ARD). She presented in infancy but was diagnosed with ARD at the age of 10 on basis of phytanic acidaemia and later confirmed to have the phytanoyl-CoA hydroxylase ((PHYH) c.164delT, p.L55fsX12) mutation. Despite repeated plasmapheresis sessions and strict dietary surveillance for 20 years, her phytanic acid levels persistently stayed above the ideal target level of 100 μmol/L but remained below 400 μmol/L. Initially the pregnancy was uncomplicated but in the third trimester of pregnancy the patient was admitted to the hospital with fluctuating hypertension, sinus tachycardia and breathlessness. The patient was compliant with diet during pregnancy and her phytanic levels were remained well controlled: 177 and 188 μmol/L in the first and second trimester, respectively. Peri-partum management required a coordinated team approach including a high-calorie and restricted diet to reduce the risk of acute metabolic decompensation. During the induced labour she required 10% dextrose infusions.

Post-partum it took the mother a long time to recover from childbirth – her appetite was poor due to post-natal depression and her body weight decreased rapidly by 11 kg within 3 weeks after childbirth, resulting in a spike in phytanic acid to 366 μmol/L. Measures were taken to minimise the risk of acute neurological decompensation. The infant was unaffected and has made normal developmental progress in the subsequent 2 years.


Adult Refsum’s disease Phytanic acid Phytanoyl-CoA hydroxylase deficiency Pregnancy 



The authors would like to thank gynaecologists and obstetricians who looked after the patient during the perinatal period for their comments on the manuscript.


  1. Baldwin EJ, Gibberd FB, Harley C, Sidey MC, Feher MD, Wierzbicki AS (2010) The effectiveness of long-term dietary therapy in the treatment of adult Refsum disease. J Neurol Neurosurg Psychiatry 81:954–957CrossRefPubMedGoogle Scholar
  2. Baldwin EJ, Harrington DJ, Sampson B, Feher MD, Wierzbicki AS (2016) Safety of long-term restrictive diets for peroxisomal disorders: vitamin and trace element status of patients treated for Adult Refsum Disease. Int J Clin Pract 70:229–235CrossRefPubMedGoogle Scholar
  3. Brown PJ, Mei G, Gibberd FB et al (1993) Diet and Refsum’s disease. The determination of phytanic acid and phytol in certain foods and application of this knowledge to the choice of suitable convenience foods for patients with Refsum’s disease. J Hum Nutr Diet 6:295–305CrossRefGoogle Scholar
  4. Burns TM, Ryan MM, Darras B, Jones HR Jr (2003) Current therapeutic strategies for patients with polyneuropathies secondary to inherited metabolic disorders. Mayo Clin Proc 78:858–868CrossRefPubMedGoogle Scholar
  5. Butte NF (2000) Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr 71:1256S–1261SPubMedGoogle Scholar
  6. Claridge KG, Gibberd FB, Sidey MC (1992) Refsum disease: the presentation and ophthalmic aspects of Refsum disease in a series of 23 patients. Eye (Lond) 6(Pt 4):371–375CrossRefGoogle Scholar
  7. DiGiovanna JJ, Robinson-Bostom L (2003) Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermatol 4:81–95CrossRefPubMedGoogle Scholar
  8. Herbert MA, Clayton PT (1994) Phytanic acid alpha-oxidase deficiency (Refsum disease) presenting in infancy. J Inherit Metab Dis 17:211–214CrossRefPubMedGoogle Scholar
  9. Jansen GA, Hogenhout EM, Ferdinandusse S et al (2000) Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum’s disease. Hum Mol Genet 9:1195–1200CrossRefPubMedGoogle Scholar
  10. Kohlschutter A, Santer R, Lukacs Z, Altenburg C, Kemper MJ, Ruther K (2012) A child with night blindness: preventing serious symptoms of Refsum disease. J Child Neurol 27:654–656CrossRefPubMedGoogle Scholar
  11. Langendonk JG, Roos JC, Angus L et al (2012) A series of pregnancies in women with inherited metabolic disease. J Inherit Metab Dis 35:419–424CrossRefPubMedGoogle Scholar
  12. Laurell S, Nilsen R, Norden A (1972) Incorporation of phytanic and linoleic acid into plasma lipids in Refsum’s disease. Clin Chim Acta 36:169–174CrossRefPubMedGoogle Scholar
  13. Lloyd MD, Darley DJ, Wierzbicki AS, Threadgill MD (2008) Alpha-Methylacyl-CoA racemase – an ‘obscure’ metabolic enzyme takes centre stage. FEBS J 275:1089–1102CrossRefPubMedGoogle Scholar
  14. Poulos A, Sharp P, Fellenberg AJ, Johnson DW (1988) Accumulation of pristanic acid (2, 6, 10, 14 tetramethylpentadecanoic acid) in the plasma of patients with generalised peroxisomal dysfunction. Eur J Pediatr 147:143–147CrossRefPubMedGoogle Scholar
  15. Ruther K (2005) Adult Refsum disease. A tapetoretinal degeneration accessible for therapy. Ophthalmologe 102:772–777CrossRefPubMedGoogle Scholar
  16. Skjeldal OH, Stokke O, Refsum S, Norseth J, Petit H (1987) Clinical and biochemical heterogeneity in conditions with phytanic acid accumulations. J Neurol Sci 77:87–96CrossRefPubMedGoogle Scholar
  17. van den Brink DM, Brites P, Haasjes J et al (2003) Identification of PEX7 as the second gene involved in Refsum disease. Am J Hum Genet 72:471–477CrossRefPubMedPubMedCentralGoogle Scholar
  18. Wierzbicki AS, Lloyd MD, Schofield CJ, Feher MD, Gibberd FB (2002) Refsum’s disease: a peroxisomal disorder affecting phytanic acid alpha-oxidation. J Neurochem 80:727–735CrossRefPubMedGoogle Scholar
  19. Wierzbicki AS, Mayne PD, Lloyd MD et al (2003) Metabolism of phytanic acid and 3-methyl-adipic acid excretion in patients with adult Refsum disease. J Lipid Res 44:1481–1488CrossRefPubMedGoogle Scholar
  20. Zolotov D, Wagner S, Kalb K, Bunia J, Heibges A, Klingel R (2012) Long-term strategies for the treatment of Refsum’s disease using therapeutic apheresis. J Clin Apher 27:99–105CrossRefPubMedGoogle Scholar
  21. Zomer AW, Jansen GA, van Der BB et al (2000) Phytanoyl-CoA hydroxylase activity is induced by phytanic acid. Eur J Biochem 267:4063–4067CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Karolina M. Stepien
    • 1
  • Anthony S. Wierzbicki
    • 2
  • Bwee T. Poll-The
    • 3
  • Hans R. Waterham
    • 4
  • Christian J. Hendriksz
    • 1
    • 5
  1. 1.Adult Inherited Metabolic Disorders, The Mark Holland Metabolic UnitSalford Royal NHS Foundation TrustSalfordUK
  2. 2.Metabolic Medicine/Chemical Pathology, Guy’s & St Thomas’ HospitalsLondonUK
  3. 3.Department of Paediatric NeurologyEmma Children’s Hospital, Academic Medical Centre, University of AmsterdamAmsterdamThe Netherlands
  4. 4.Academic Medical Centre, Laboratory Genetic Metabolic DiseasesUniversity of AmsterdamAmsterdamThe Netherlands
  5. 5.Paediatrics and Child Health, Steve Biko Academic UnitUniversity of PretoriaPretoriaSouth Africa

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