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

Abstract

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 mmol/L but remained below 400 mmol/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 mmol/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 mmol/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.

Pregnancy outcome in Refsum disease: Affected fetuses and children born to an affected mother

“…Only in one instance, fetal exposure to PA has been postulated for a young boy affected by a very earlyonset ARD hypothetically born to a homozygous mother. 21 In conclusion, as previously highlighted, 11 this case of a homozygous woman suffering from ARD and pregnant with affected fetuses suggests that the risk of developing disease manifestations is higher for the mother during pregnancy than for her fetus. Whereas additional cases need to be investigated, prenatal diagnosis may not be indicated in an affected mother who follows regular dietary therapy during pregnancy and whose plasma PA levels are monitored.…”

“…The pregnancy management of an ARD female patient with a heterozygous fetus has already been reported. 11 In this situation, the risk for the fetus remains low because of the residual phytanoyl-CoA hydroxylase activity. However, for the mother, the risk of exacerbation of ARD is higher, on account of changes in lipid metabolism during pregnancy, especially lipolysis in the third trimester.…”

“…Pregnancy outcomes in a homozygous female have already been described; her heterozygous fetus developed normally. 11 Here, we describe the first published case of a homozygous woman affected by ARD, who was repeatedly pregnant with homozygous fetuses.…”

Impact of pregnancy on inborn errors of metabolism

“…Phytanic acid levels are managed by diet-restriction ± plasmapheresis and avoidance of lipolysis, which can release phytanic acid from adipose tissue triggering neurological decompensation. A childhood-onset Refsum’s disease pregnancy, reporting reduced phytanic acid control late gestation, despite close dietetic management [ 191 ], likely reflected accelerated lipolysis [ 12 , 14 ].…”

Therapeutic Apheresis in Neurology

“…Therapeutic strategy is ultimately determined by monitoring the patient ś PA level, clinical signs and symptoms, and the need to control or prevent exacerbations of the disease [61]. To date, no cure exists for Refsum´s disease, but phytanate levels in patients can be reduced by TPE and a strict diet [62,63].…”