Peroxisomal Disorders Treatment & Management

Updated: Jul 29, 2020
  • Author: Hoda Z Abdel-Hamid, MD; Chief Editor: Stephen L Nelson, Jr, MD, PhD, FAACPDM, FAAN, FAAP, FANA  more...
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Medical Care

Management and treatment are based on the disorder, the age of onset, and the rate of progression as well the risks and benefits associated with the available therapies. Other considerations include parent expectations and the quality of life.

In March 2015, cholic acid (Cholbam) was approved by the FDA for adjunctive treatment of peroxisomal disorders, including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption. Bile acids facilitate fat digestion and absorption by forming mixed micelles, and they facilitate absorption of fat-soluble vitamins in the intestine. The mechanism of action of cholic acid has not been fully established; however, it is known that cholic acid and its conjugates are endogenous ligands of the nuclear receptor, farnesoid X receptor (FXR).

Efficacy of cholic acid for peroxisomal disorders was assessed in a single arm, treatment trial involving 29 patients treated over an 18-year period. An extension trial followed 10 of these patients and enrolled an additional 2 patients with interim efficacy data available for 21 additional months. The majority of patients were younger than 2 years at the start of cholic acid treatment (range 3 weeks to 10 years). Response to treatment was evaluated by improvements in baseline liver function tests and weight. Responses were noted in 46% of patients with evaluable data. Forty-two percent of patients survived >3 years. [9, 10]

The treatment can be specific to the disorder, such as in the case of Refsum disease, which includes elimination of the toxic substance.

  • Because phytanic acid is exclusively of dietary origin (butter, cheese, beef, lamb, and some fish), its restriction can reduce its blood and tissue levels in 1-2 years, and the neurotoxic events can be significantly limited.

  • Long-term follow-up has shown that dietary restriction improves peripheral-nerve and cardiac function and stabilizes the retinal abnormalities and hearing deficit.

  • In sick patients, phytanic acid levels can be rapidly lowered with plasma exchange; this may reverse some symptoms. Alternative means to decrease phytanic acid levels is w-oxidation by means of the cytochrome P-450 enzyme; however, this line of therapy remains experimental.

  • Extracorporeal apheresis is another therapeutic approach that may result in in long-term improvement or stabilization in patients with progressive Refsum disease. [11]

In patients with hyperoxaluria type I, combined liver-kidney transplantation has shown the greatest promise.

In patients with X-ALD, oral administration of a mixture of glyceryl trioleate and trierucate oils (also referred to as Lorenzo oil) normalizes levels of saturated VLCFA in plasma within 4 weeks. However, consider the following:

  • Clinical rexults in patients who already had neurologic involvement have been disappointing.

  • The therapy also does not appear to alter the rate of progression of endocrine abnormalities. However, it may diminish the frequency and severity of subsequent neurologic involvement, and it has been recommended in asymptomatic boys with X-ALD after the age of 1 year.

  • Bone marrow transplantation reversed neurologic, cognitive, and neuroradiological abnormalities in 1 patient who was treated when nervous-system involvement was still mild. Results in patients with advanced disease have been disappointing.

  • A French team has reported on autologous hematopoietic stem cell (HCT) gene therapy with a lentiviral vector in 2 patients with X-ALD. Progression of cerebral demyelination in the 2 patients began to stop 14-16 months after infusion of the genetically corrected cells, a clinical outcome comparable to that achieved by allogeneic HCT. [12]

  • Several laboratories are attempting to develop a genetic model of ADL in knock-out mice, with the aim of evaluating the efficacy of gene therapy.

  • Currently, HSCT is not indicated for AMN and Zellweger syndrome. [13]

Postnatal therapy of patients with disorders of peroxisome assembly is limited by the many abnormalities present at birth.

  • Recent data have demonstrated that patients with ZWS, NALD, and IRD have decreased blood tissue levels of docosahexanoic acid (DHA) and have suggested an important role of this substance in retina and brain. On this basis, Martinez et al initiated a therapeutic trial of this substance in patients with NALD. Improved visual and neurologic function was observed in 1 patient. [14]

  • Noguer and Martinez subsequently reported improved visual function with DHA ethyl ester treatment in 23 patients with peroxisomal disorders, 2 with classic Zellweger syndrome and 1 with D-bifunctional protein deficiency. [15]

  • The development of compounds aimed at limiting the accumulation of VLCFA in fibroblasts is under investigation. [16]


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