General information
• Peroxisomes are small organelles found in all tissues. It has over 35 anabolic and catabolic functions in the body. They are found in all cells except mature erythrocytes.
• The most important tasks of peroxisomes and laboratory findings that may occur in Zellweger spectrum disorders are as follows:
- Oxidation of very long chain fatty acids (VLCFA) is impaired and plasma VLCFA levels increase.
- Plasmalogen synthesis is disrupted and its plasma level decreases
- Phytanic acid oxidation is impaired and its plasma level increases.
- Bile acid synthesis and conjugation is impaired and bile acid intermediates increase
- Deterioration in oxidation of L-pipecolic acid and increase in its plasma level.
- Urine dicarboxylic acid secretion is increased.
• Considering the genetic transmission of diseases, all are autosomal recessive except for X-linked adrenoleukodystrophy (the most common peroxisomal disease).
Pathology
• Metabolites accumulated in diseases impair neuronal migration, may cause micronodular cirrhosis of the liver, renal cysts, chondrodysplasia punctata, corneal infiltrates, retinopathy, cataracts, congenital heart disease and dysmorphic facial appearance.
Classification
• The disease is collected in 2 important groups.
Disturbances in peroxisome biogenesis
Zellweger spectrum disorders
• Zellweger's syndrome
• Neonatal adrenoleukodystrophy
• Infantile Refsum disease
• Rhizomelic chondrodysplasia punctata
Diseases due to peroxisomal single enzyme defect
• X-linked adrenoleukodystrophy
• Classic Refsum's disease
• Acyl CoA oxidase deficiency
• Bifunctional enzyme deficiency
• 2-Methylacyl CoA racemase deficiency
Peroxisomal Diseases
1- Zellweger syndrome (cerebrohepatorenal syndrome)
• Typical mongoloid facial appearance and Down stigmatism (palpebral fissure, epicanthal fold, nasal root flattening)
• Severe neonatal hypotonia and resistant convulsions (myoclonic)
• Eye abnormalities (cataract, glaucoma, corneal opacification, Brushfield spots, pigmentary retinopathy, nystagmus)
• Macrocephaly
• Postnatal growth retardation, liver disease, renal cyst
Diagnosis:
Elevated serum VLCFA, pipecolic acid, phytanic acid levels; low plasminogen and bile acid
2- Rhizomelic chondrodysplasia punctata (RCDP)
• Rhizomelic disproportionate short stature
• Point (punctate) ossifications in the metaphyseal regions of the proximal bones radiologically
• Cataract
• Mental retardation
• Ichthyosyphoma erythrodermis
• Weight, height and head circumference <3. percentile
3- CLASSIC REFSUM DISEASE
• OR is a disease that develops due to phytanoyl coenzyme A hydroxylase deficiency and is inherited.
• Classic findings are retinitis pigmentosa and night blindness, ichthyosis, peripheral neuropathy and ataxia.
• It may not show symptoms until adolescence and adulthood.
• Sometimes cardiac arrhythmias accompany the picture.
• Unlike Infantile Refsum disease, mental development is normal. Diagnosis: Increase in serum phytanic acid and decrease in pristanic acid are diagnostic. Early diagnosis is important because phytanic acid-restricted diet can reverse the findings.
4- X Linked Adrenoleukodystrophy ALD
• Peroxisomal Lignoseroyl - Co A Ligase is missing and hexacosanoic acid (C: 26) accumulates.
• The first 3-4 years of life are asymptomatic.
• The childhood cerebral form presents between the ages of 4 and 8 years, and the most common initial symptom is hyperactivity and deterioration in school performance. Visual and hearing impairment, ataxia, convulsions and strabismus are other findings. Inadequate cortisol response to ACTH stimulation is present in 85% of patients. There are also slow-progressing adolescent ALD, adrenomyeloneuropathy causing paraplegia involving the spinal cord, and Addison phenotype forms with only adrenal insufficiency.
Diagnosis
The most specific and most important laboratory finding is increased VLCFA levels in serum, erythrocyte and tissue cultures.
• In cranial MRI; Symmetrical periventricular white matter degeneration is seen in the occipital and posterior parietal regions.
Treatment
Bone marrow transplantation is the best treatment. Lorenzo's oil (4:1 glyceryl triolerate and glyceryl trierucate) cannot stop the progression of the disease in cases with cerebral involvement.
Interferon Beta and immunosuppressants are not effective.