Affiliations: Saint-Georges Hospital, Lebanon
Journal reference: https://doi.org/10.1016/j.jfo.2017.08.010
Summary: Children with glutathione synthetase deficiency can have many symptoms that vary in severity. The most severe cases can lead to retinal dystrophy and macular edema, both of which alter their vision. This article describes the symptoms and how to treat them.
Children with glutathione synthetase deficiency lack a very important protein called glutathione that plays a protective role in the retina. They suffer from a variety of symptoms that can range from mild, like anemia, to severe, like decreased movements and slow speech.
Glutathione Synthetase Deficiency is classified into three types:
1) Mild: it mainly consists of hemolytic anemia (the abnormal destruction of red blood cells)
2) Moderate: it also includes hemolytic anemia as well as abnormal increase in the acidity of the blood and body tissus. Symptoms are apparent directly after birth.
3) Severe: affected children have both hemolytic anemia and abnormally increased acidity in their bodies, plus a variety of neurological symptoms such as seizures (abnormal electrical activity in the brain leading to incoherent limb and body movements), slowed movements and slowed speech. They might additionally suffer from intellectual disability and an increased risk of bacterial infections.
Children with severe glutathione synthetase deficiency also suffer from retinal dystrophy and cystoid macular edema.
Retinal dystrophy is a slow and progressive destruction of layers of their retina, in a non-inflammatory process. The retina is a thin layer of tissue located in the back of our eye that is responsible for our vision. Our cornea and lens (both transparent structures, acting like the lenses of a camera) are responsible for focusing images on the retina. Our retina is made of 10 microscopic layers, each carrying out a vital function. The most important part of our retina, the part that is responsible for producing the best image one sees, is called the ‘’macula’’ and is in the center of our retina. Patients who suffer from severe glutathione synthetase deficiency can accumulate fluid in the macula (cystoid macular edema) which will interfere significantly with their quality of vision and with time if left untreated can destroy the layers of their retina slowly and permanently.
In this study the fluid accumulation observed in homozygous twins was treated with eye drops called dorzolamide and pills called acetazolamide, both of which belong to the same family of drugs called carbonic anhydrase inhibitors. These drugs work by sucking the abnormally accumulated fluid out of the eye.
Results showed that with time the fluid disappeared when using acetazolamide alone or in combination with the dorzolamide drops. This healing effect was preserved even after both medications were stopped and the children with cystoid macular edema stopped accumulating fluid in their retinas.
Take home message: The combination of dorzolamide drops and acetazolamide pills does seem effective in treating the accumulation of fluid underneath the retina in children with glutathione synthetase deficiency.