SNP Shot: Genomic Insights

Zellweger spectrum disorder (ZSD) is a condition affecting multiple body systems. Its severity is often classified as severe, intermediate, or mild.

In severe ZSD, symptoms typically appear at birth and worsen over time. Infants often exhibit weak muscle tone (hypotonia), difficulty feeding, hearing and vision impairment, and seizures. These issues arise from reduced myelin, the protective covering of nerves crucial for efficient nerve impulse transmission. The myelin-containing part of the brain and spinal cord is called white matter. The loss of myelin (demyelination) results in white matter loss (leukodystrophy).

Children with severe ZSD also experience life-threatening complications in organs and tissues such as the liver, heart, and kidneys. The liver or spleen may be enlarged. Skeletal abnormalities, like a large space between skull bones (fontanelles) and distinctive bone spots (chondrodysplasia punctata) visible on X-rays, can occur. Eye abnormalities, including cloudy lenses (cataracts) or involuntary eye movements (nystagmus), are also possible. Severe ZSD includes characteristic facial features like a flattened face, broad nasal bridge, high forehead, and widely spaced eyes (hypertelorism). Sadly, children with severe ZSD usually do not survive beyond their first year.

Individuals with intermediate or mild ZSD have a wider range of symptoms that progress more slowly than the severe form. Symptoms may not appear until late infancy or early childhood. Common features include hypotonia, vision and hearing problems, liver dysfunction, developmental delays, and some degree of intellectual disability. Most people with the intermediate form live into childhood, while those with the mild form may reach adulthood. Rarely, individuals with very mild ZSD only experience developmental delay in childhood and hearing or vision problems in adulthood, without developing other characteristic features.

The severe, intermediate, and mild forms of ZSD were initially considered separate disorders. The severe form was termed Zellweger syndrome, the intermediate form neonatal adrenoleukodystrophy (NALD), and the mild form infantile Refsum disease. These were later recognized as variations of the same condition and grouped under the umbrella term Zellweger spectrum disorder.

Inheritance:

ZSD is inherited in an autosomal recessive manner. This means that an affected individual inherits a mutated copy of the responsible gene from each parent. The parents, carrying one copy of the mutated gene each, are usually unaffected and do not display symptoms of the disorder.