Alcohol supplementation in Rhizomelic chondrodysplasia punctata
in the Netherlands.

Rationale: Plasmalogen deficiency is the main biochemical defect in patients with Rhizomelic chondrodysplasia punctata (RCDP); a peroxisomal disorder characterized by skeletal abnormalities and severe neurological (both mental and motor) impairments. RCDP patients can have either a mild or a severe phenotype depending on the rest-capacity to synthesize plasmalogens. Most patients with the severe phenotype of RCDP die in their first decade of life. Currently there is no therapy available. Batyl alcohol is a naturally occurring mono ether glycerol. In vitro studies in human fibroblast cell lines and in vivo studies in the mice model for RCDP and Zellweger syndrome patients showed that plasmalogen levels can be restored by batyl alcohol.
Objective: The central aims of this study are to evaluate whether the plasmalogens in RCDP patients can be increased by batyl alcohol supplementation and to find clinical effects of oral batyl alcohol supplementation.
Study design: Cohort study
Study population: All patients with biochemically proven RCDP can enter this study. The aim is to include 10 patients in a study period of 2 years.
Intervention: Patients will be taking 5 to 50 mg/kg batyl alcohol daily. The batyl alcohol will be administered orally.
Main study parameters/endpoints: the primary endpoints in this study will be an increase in plasmalogen content of erythrocytes to at least 50% of normal C18:0 DMA/C18:0 fatty acid values in patients with the severe phenotype and to at least 90% of normal C18:0 DMA/C18:0 fatty acid values in patients with the milder phenotype of RCDP and an increase in growth and bone development. Secondary endpoints include 1) increased plasmalogen content in sputum 2) improving quality of life scores (TAPQOL) and 3) stabilization or improvement in nerve conduction. Stabilization in MRI/MRS will be our tertiary endpoint.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will take batyl alcohol capsules every day. No side-effects of alkylglycerols including batyl alcohol have been described in literature. An extended work-up / follow-up will be at baseline and after 12 months, including a physical examination, blood sampling, urine sampling, electroneurophysiological examinations, skeletal X-rays, joint function tests and MRI/MRS. The MRI/MRS, sputum collection and the blood sampling will be performed during narcosis. For these investigations the child will be admitted to the paediatric ward of the AMC. At 2, 4, 8, 12, 26, 39 weeks the patient will come to the outdoor clinic for a physical examination and blood and urine sampling. The investigators will try to minimize the burden for patients and their parents by minimizing the hospitalisation time and by performing the invasive studies during the narcosis. Medical X-ray burden is minor.

Plasmalogens can be synthesized out of batyl alcohol (naturally occuring alkylglycerol) in patients with the peroxisomal disorder rhizomelic chondrodypslasia punctata (RCDP), bypassing the peroxisomal steps in the pathway.

1. batyl alcohol supplementation 5 - 50 mg/kg/day

2. blood sampling

3. X-ray skeleton

4. Dexa scan

5. MRI

6. EEG

7. VEP

8. BAEP

9. EMG

10. SSEP

11. questionnaire well being