Neurological Manifestations

The Wulf family attended the webinar on Patient-Focused Drug Development for Neurological Manifestations of Inborn Errors of Metabolism, June 10, 2014, and participated in the discussion, polls, and made the following public comment.

Our son Matthew, diagnosed with Zellweger’s Syndrome at nine weeks of age, was given six to twelve months to live. Symptoms of this rare disorder (1/50,000) include cholestatic jaundice in newborns, failure to thrive, bile acid deficiency, DHA deficiency, cholesterol deficiency, adrenal insufficiency, leukodystrophy, seizure disorder, impaired synthesis of plasmalogen, hypotonia, hyporeflexia, ataxia, blindness, and sensorineural hearing loss.   To correct the deficiency of DHA, at five months of age Matthew began treatment of 200 mg/day of DHA-ethyl ester in Barcelona, Spain, due to it not being available in the United States.  Typically children with peroxisomal disorders cannot break down the commonly available DHA triglycerides (DHA-TG) because their liver’s inability to synthesize and release very low density lipoprotein (VLDL) particles due to a reduced synthesis of phophalidylcholine.  DHA-EE bypasses the initial step of entry synthesis and once into the body it is then converted into a triglyceride for use.

Not only did the DHA-EE singularly correct the deficiency of DHA in Matthew, but it produced spin-off effects in several other areas, improving his plasmalogen level, lowering his VLCFA (very long chain fatty acids), lowering his liver enzyme tests (AST, ALT, gamma GT), improving muscle weakness, myelination, and vision.  However, regardless of the published spectacular results in most children with Zellweger’s who are treated early with the DHA-EE, it is still not an available treatment in the United States.

We would like to not only see early diagnosis through screening these children for bile acid deficiency when they present with newborn cholestatic jaundice, but also to see the treatment of DHA-EE provided to prevent irreversible damage and to give them the best quality of life possible.