pediatrics
Peroxisomal Disorders
X linked adrenoleukodystrophy
This disorder is caused by deficiency of the peroxisomal membrane transporter ALDP, which is coded for by the geneABCD1. This is an X-linked gene and thus the disorder manifests primarily in males. Currently, > 900 mutations have been identified (seeALD Info). The cerebral form affects 40% of patients. Onset occurs between age 4 years and 8 years, and Symptoms and Signs progress over time to severe behavioral problems, dementia, and vision, hearing, and motor deficits, causing total disability and death 2 to 3 years after diagnosis. Milder adolescent and adult forms have also been described. About 45% of patients have a milder form called adrenomyeloneuropathy (AMN); onset occurs in the 20s or 30s, with progressive paraparesis, and sphincter and sexual disturbance. About one third of these patients also develop cerebral symptoms. Patients with any form may also develop Addison Disease ; about 15% have isolated Addison disease without neurologic involvement. Diagnosis of X-linked adrenoleukodystrophy is suspected by isolated elevation of VLCFA and confirmed by gene sequencing. Bone marrow or Hematopoietic Stem Cell Transplantation may help stabilize symptoms in some cases. Adrenal steroid replacement is needed for patients with adrenal insufficiency. Dietary supplement with a 4:1 mixture of glyceryl trioleate and glyceryl trierucate (Lorenzo’s oil) can normalize plasma VLCFA levels but does not appear to stop neurologic degeneration in symptomatic patients. However, if given to boys before symptom onset, it may slow disease progression; the exact benefit has not been determined. Gene therapy trials are currently underway and have shown some preliminary success. 