Zellweger Spectrum (Zellweger Syndrome, Neonatal Adrenoleukodystrophy, and Infantile Refsum Disease)
Zellweger Syndrome is a rare form of leukodystrophy affecting infants, of which a reduction or absence of peroxisomes in the cells of the liver, kidneys, and brain is characteristic. The major manifestations of Zellweger Syndrome include unusual problems in prenatal development, an enlarged liver, high levels of iron and copper in the blood, and vision disturbances.
Infants with Zellweger Syndrome have the disease from birth, and it is usually fatal within six months. It can often be recognized at birth due to profound lack of muscle tone; some infants may be unable to move. Prenatal growth failure, despite a normal period of gestation, are another manifestation of Zellweger, along with unusual facial characteristics, mental retardation, the inability to suck and/or swallow, and liver enlargement. Less commonly there may be vision problems and congenital heart lesions. Jaundice and/or gastrointestinal bleeding due to deficiency of a coagulation factor in the blood can also occur. This There may also be abnormal bleeding that can be corrected by giving Vitamin K. Infections should be guarded against carefully to delay complications, as pneumonia or respiratory distress may develop if infections are not prevented or controlled.
Zellweger Syndrome is inherited as an autosomal recessive trait. The deficiency or absence of the microbodies known as peroxisomes causes an accumulation of very long chain fatty acids the in body. The exact cause of the lack of these peroxisomes is not yet known. Early diagnosis and prenatal detection can be made through the study of the very long chain fatty acids which accumulate in the absence of peroxisomes.
Treatment of Zellweger Syndrome is symptomatic and supportive.
Neonatal ALD is autosomal recessive in its pattern of inheritance, so unlike the other form of ALD it affects both males and females. The disorder is now fairly easy to diagnose through biochemical tests, which demonstrate abnormally high levels in the tissues and body fluids of the very long chain fatty acids typical of ALD.
Neonatal ALD is similar to the Zellweger cerebrohepatorenal syndrome, and may actually represent a milder variant of Zellweger. While there is no doubt that it is distinct from X-linked ALD, the exact classification of this neonatal form of ALD is still indeterminate.
Individuals with Neonatal ALD suffer severe or profound mental retardation and impaired psychomotor development, together with possible impaired liver function and retarded growth.
The clinical presentation and course of neonatal ALD is still not fully defined. It may take the form of an extremely severe illness with intractable seizures during the earliest part of life, or manifest as a milder form where the sufferer may survive to their mid-teens or possibly longer.
Treatment of neonatal ALD is symptomatic and supportive.
Patients with the infantile form of this phytanic acid storage disorder show differences from the adult form. Early onset, associated with mental retardation, retinal pigmentation, hearing defects, enlargement of the liver, osteoporosis and failure to thrive.
Clinically, Infantile Refsum's Disease shares some features with Adrenoleukodystrophy and Zellweger Syndrome, in that while IRD sufferers share the phytanic acid accumulation of adult Refsum's, they also show the defective metabolism of bile acid as in Zellweger.
IRD is slowly progressive if left untreated, but as with adult Refsum's Disease, a diet which limits the intake of phytanic acid presents a hopeful treatment.
Further information can be obtained from:
Zellweger Spectrum (Zellweger Syndrome, Neonatal Adrenoleukodystrophy, and Infantile Refsum Disease