The PBD are a rare group of inherited disorders due to the failure to form functional cellular peroxisomes. Most patients have progressive hearing and visual loss, leading to deafness and blindness, as well as neurological deterioration. There are no therapies for this disorder. A misfolded protein with residual function, PEX1-Gly843Asp, represents one third of all mutant alleles. Using patient cell lines with this mutation, we reported the recovery of peroxisome functions by treatment with Betaine, acting as a nonspecific chemical chaperone for the misfolded PEX1 protein. Betaine, or trimethylglycine, is a Health Canada and FDA approved orphan drug for the treatment of homocystinuria and is used by us safely and regularly in genetic medicine. We will perform a 6 month pilot study with 12 patients to test the hypothesis that Betaine, at recommended doses, can recover peroxisome biochemical functions in blood.

NCT01838941

Conditions

1. Peroxisome Biogenesis Disorders

Interventions

1. Drug: Betaine

MeSH:Peroxisomal Disorders Disease

A misfolded protein with residual function, PEX1-Gly843Asp, represents one third of all mutant alleles. --- Gly843Asp ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D ---

Denver Developmental Screening Test expressed in years and months.. Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Inclusion Criteria: - Males or females - Any age - Peroxisome Biogenesis Disorder (PBD) confirmed by biochemical analysis of at least two peroxisomal enzyme parameters: - Elevated plasma VLCFA (C26/22) > 0.02 - Elevated plasma branched chain pristanic acid > 0.3 μg/ml - Reduced red blood cell plasmalogen levels (C16:0DMA/C16:0 Fatty acid) < 0.07 - PBD clinical syndromes: neonatal adrenoleukodystrophy (NALD) or infantile Refsum disease (IRD) - Genotype PEX1-G843D/G843D, PEX1-G843D/I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Expected survival of at least 6 months Exclusion Criteria: - Genotypes other than PEX1 G843D/G843D, PEX1-G843D//I700fs, or PEX1-G843D and any second PEX1 mutation that is predicted to be null - Patient already treated with betaine Peroxisome Biogenesis Disorders Peroxisomal Disorders Disease Peroxisome biogenesis disorders (PBD) are a group of inherited conditions caused by faulty assembly of peroxisomes, structures located inside cells that regulate levels of important fats and lipids in the body. --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D --- --- G843D ---

Using this test, they have uncovered that Betaine can improve the function of the peroxisome, when the defect is caused by a PEX1-Gly843Asp mutation, and as such may improve the overall health of child suffering from PBD. Betaine is a medication already available as a powder for oral solution, for another rare disease. --- Gly843Asp ---

At the current stage of scientific knowledge, it is a critical next step to evaluate the benefit of betaine in children having a PBD due to a PEX1-Gly843Asp mutation, to ensure that the medication is safe and to measure the level of improvement of the function of the peroxisome. --- Gly843Asp ---