Prader-Willi-2

Summary

Mitochondrial distress with oxidative stress and extreme glutathione up-regulation is exacerbated by glycine conjugation insufficiency and intestinal bacterial overgrowth.

This content was created by the Metametrix Institute

History

Prader-Willi Syndrome (PWS) is a disorder of chromosome 15. Prevalence: 1:12,000- 15,000 (both sexes, all races) Major characteristics: hypotonia, hypogonadism, hyperphagia, cognitive impairment, difficult behaviors. Major medical concern: morbid obesity.

Approximately 70% of cases have a non-inherited deletion in the paternally contributed chromosome 15; approximately 25% have maternal uniparental disomy (UPD), two maternal 15s and no paternal chromosome 15. Hypothalamic dysfunction is thought to be the cause of the disordered appetite/satiety function characteristic of PWS.

Therapy reported in this case: growth hormone therapy with concomitant IGF-1 increase along with thyroid hormone.

Age

3

Gender

Male

Description of Results

Extreme glutathione demand is shown in the pattern of greatly elevated a-hydroxybutyrate, sulfate (upper limit of 450 implemented after this report), and pyroglutamate. Both oxidative challenge (indicated by high 8-OHdG) and hepatic detoxification challenge (indicated by elevated benzoate) are present and may be contributory to the glutathione demand.

Bacterial overgrowth to this degree can lead to insufficiencies of biotin and other vitamins through interference with absorption or with favorable bacterial production of the nutrient.

Recommendations

Focus on reducing intestinal bacterial growth rates, assisting glycine conjugation (oral glycine) and supporting glutathione status (N-acetylcysteine, etc.)

Support B-complex and CoQ10 status.

Other Comments

In this case the disorder is associated with multiple organic acidurias, many of which may respond to nutrient supplementation. There is significant bacterial dysbiosis and hepatic glycine conjugation difficulty.