Childhood Refsum disease (IRD) is the mildest variant of peroxisome biogenesis disorders, spectrum of Zellweger syndrome (PBD-ZSS). It is characterized by hypotonia , retinitis pigmentosa , developmental delay, sensorineural hearing loss, and liver dysfunction. There is an overlapping phenotype between IRD and neonatal adrenoleukodystrophy (NALD).
- Synonym: IRD
- Heredity: Autosomal recessive
- Age of onset or appearance: Any age
Summary
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- 1 Epidemiology
- 2 Etiology
- 3 Diagnostic methods
- 1 Differential diagnosis
- 2 Prenatal diagnosis
- 4 Genetic advice
- 5 Management and treatment
- 1 Psychological Support
- 6 Forecast
- 7 Sources
epidemiology
The prevalence at birth of PBD-ZSS is estimated to be 1 / 50,000 in North America and 1 / 500,000 in Japan . More than half of the patients with PBD-ZSS have the NALD-IRD forms. Clinical description IRD begins at birth or early childhood, but the manifestations can be so subtle that there is no diagnosis until adulthood. In childhood, symptoms may include nystagmus , hypotonia , sensorineural hearing loss, stunted growth, facial middle third dysmorphism, and hepatomegaly . Liver dysfunction causes jaundice in infancy and sometimes episodes of intracranial bleeding due to coagulopathy. In childhood, progressive retinitis pigmentosa, developmental deficits, and hypotonia have been observed. Most motor milestones are achieved, albeit with delay, and communication with few words or signs. In older children, adrenal insufficiency and calcium oxalate kidney stones may occur . Leukodystrophy can occur with loss of previously acquired skills at any age and can stabilize or progress and be fatal. Atypical presentations have been described.
Etiology
PBD-ZSS is caused by mutations in one of the 13 PEX genes that encode peroxins that lead to abnormal peroxisome biogenesis.
Diagnostic methods
IRD is suspected on physical examination and confirmed by biochemical evaluation. Levels of very long chain fatty acids in plasma (VLCFA) indicate defects in peroxisomal fatty acid metabolism with high plasma concentrations of C26: 0 and C26: 1 and high levels of C24 / C22 and C26 / C22. The concentrations of C16 and C18 plasmalogens in the erythrocyte membrane are usually reduced, but may be normal. The levels of plasma pipecolic acids and intermediate bile acids (THCH and DHCA) increase. Occasionally, VLCFA levels and enzyme assays in fibroblasts may be within the normal range, requiring evaluations in expert laboratories. Sequencing analyzes of all 13 PEX genes can be performed.
Differential diagnosis
Differential diagnosis includes: Usher syndrome I and II, other PBD-ZSS disorders, individual enzyme defects in peroxisome fatty acid beta-oxidation, and disorders with severe hypotonia , neonatal seizures, liver dysfunction, or leukodystrophy . IRD should not be confused with adult Refsum disease.
Prenatal diagnosis
Prenatal study of cultured amniocytes and chorionic villi are possible for VLCFA synthesis of plasmalogens. If the two disease-causing alleles have been identified in the parents, prenatal diagnosis and preimplantation genetic diagnosis can be made.
Genetic advice
- IRD is inherited in an autosomal recessive manner.
Management and treatment
There is no cure for IRD. Cataracts should be removed in early childhood and glasses, and hearing aids, should be worn by those with hearing disabilities, and cochlear implants should be considered when hearing loss is profound. The coagulopathy liver can be treated with vitamin K and can improve liver function in primary bile acid therapy. A gastrostomy tube may be necessary to allow adequate calorie intake. Foods rich in phytanic acid should be restricted . Standard epileptic drugs are used for seizures. There will be a permanent monitoring of hearing , vision and liver function.
Psychological Support
This support should include not only the patient but also brothers and sisters of the affected children, parents and other family members.
Forecast
There is great variability in life expectancy, medical complications, and preservation of neurological functions. Most patients survive childhood, and can reach adulthood.
