Winter 2023 OAA Newsletter (Digital Version Available Now!)
April 5, 2023
3-methylcrotonyl-CoA carboxylase deficiency is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down proteins containing a particular building block (amino acid) called leucine. Infants with this disorder appear normal at birth but usually develop signs and symptoms during the first year of life or in early childhood. The characteristic features of this condition, which can range from mild to life-threatening, include feeding difficulties, recurrent episodes of vomiting and diarrhea, excessive tiredness (lethargy), and weak muscle tone (hypotonia). If untreated, this disorder can lead to delayed development, seizures, and coma. Early detection and lifelong management (following a low-protein diet and using appropriate supplements) may prevent many of these complications. In some cases, people with gene mutations that cause 3-methylcrotonyl-CoA carboxylase deficiency never experience any signs or symptoms of the disorder.
What else is it called?
What causes it?
Glutathione synthetase deficiency was first described in the 1970’s as a rare autosomal recessive disorder in which the body cannot produce the molecule glutathione. Glutathione is an important molecule which neutralises unstable molecules that are produced through energy production, building DNA, essential proteins and other fundamental properties for the body.
Mutations in the inherited GGS gene causes this condition, this gene provides instructions for making the enzyme glutathione synthetase which can break down glutathione. With this disorder the body is unable to break down glutathione or may only be able to break it down in small quantities.
Glutathione synthetase deficiency falls into 3 subtypes; mild, moderate and severe. Mild glutathione synthetase deficiency usually leads to the destruction of red blood cells [haemolytic anaemia]. Individuals with the moderate version of this condition may experience symptoms. With the severe form of this condition, individuals may experience neurological dysfunctions.
How common is it?
This condition has been found in no more than 70 people worldwide, with no preference over males or females.
What are the signs and symtoms?
The signs and symptoms of this Disorder are dependent upon the subtype one may be diagnosed with. Some of the more common symptoms one may experience are:
How is it diagnosed?
A diagnosis for this condition may be considered when your child experiences metabolic acidosis. This is suggestive of a metabolic condition. A doctor may order a blood test which involves a sharp needle being placed into your arm to get a sample of blood to test for levels of glutathione or a urine test to test your urine for levels of this metabolite.
Can it be treated?
Unfortunately, there is no treatment for this condition, treatment generally relies upon the management of the symptoms experience for the specific subgroups of the condition. Treatment may therefore include doses of sodium bicarbonate to counteract the low levels of glutathione and supplementation of vitamins to interact with free radical damage within the body.
People diagnosed with this condition also require a lot of follow up appointments at their local doctors, pediatrician or hospital.
Do my family need to be tested?
Autosomal recessive disorder.
Glutathione synthetase deficiency can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier.
If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.
If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.
Once you are diagnosed, you can speak to a genetic counselor. They can explain how you may have inherited Glutathione synthetase deficiency. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own.
