Introduction
γ-glutamylcysteine synthetase deficiency disorder is rare, and medical literature mentions nine patients in seven families affected by this enzyme deficiency genetic disorder. γ-glutamylcysteine synthetase is an important enzyme that is responsible for glutathione synthesis. Glutathione is responsible for hemoglobin production in the human body. Deficiency of the enzyme γ-glutamylcysteine synthetase leads to anemia and associated symptoms in the individuals suffering from it. Glutathione is a tripeptide (a molecule containing three amino acid residues). Glutamate, cysteine, and glycine are the three amino acids that together form glutathione. Deficiency of γ-glutamylcysteine synthetase enzyme can cause hemolytic anemia, neuromuscular function disorder, and aminoaciduria (abnormal amino acid concentration in urine). γ-glutamylcysteine synthetase deficiency disorder has an autosomal recessive inheritance pattern.
Can a Child Get γ-Glutamylcysteine Synthetase Deficiency From Their Parents?
γ-glutamylcysteine synthetase deficiency is an inherited genetic disorder with an autosomal recessive inheritance pattern. This means that both the parents, the mother and the father of the individual affected by γ-glutamylcysteine synthetase deficiency, carry the defective genes. Still, the parents do not show the symptoms of the disease. Genetic mutations (structural changes in the genes) are associated with γ-glutamylcysteine synthetase deficiencies. There is a twenty-five percent chance or probability that parents who are carriers of the defective gene will have children with γ-glutamylcysteine synthetase deficiency disorder. Genetic mapping in the prenatal stage can help doctors analyze the likelihood of the child suffering from γ-glutamylcysteine synthetase deficiency.
What Is Red Blood Cell Enzyme Disorder?
Hemolytic anemia is the most common indicator of red blood cell enzyme disorder.
γ-glutamylcysteine synthetase deficiency, pyruvate deficiency, and glucose-6-phosphate dehydrogenase deficiency disorder are a few red blood cell enzyme disorders. Red blood cell destruction increases in these disorders leading to lowered red blood cell count and hemoglobin count. This condition is called hemolytic anemia. In medical terms, hemolytic anemia is also called normocytic normochromic anemia because red blood cells are not associated with structural deformity in this type of anemia. Still, the red blood cell count is reduced due to increased red cell destruction. Genetic mutations are noted to be associated with these enzymatic disorders. Researchers have pointed out four mutations directly linked with red blood cell enzyme disorder.
What Are the Clinical Features of γ-Glutamylcysteine Synthetase Deficiency?
The following are the most common clinical features noted in γ-glutamylcysteine synthetase deficiency:
-
Hemolytic Anemia: Mild hemolytic anemia is noted in these individuals. Hemolytic anemia is caused due to increased red blood cell destruction. γ-glutamylcysteine synthetase deficiency hampers the red blood cell production cycle (glutathione cycle), leading to increased destruction of red blood cells.
-
Spinocerebellar Degeneration: It is a very rare condition. Medical research papers state that one of the siblings suffering from γ-glutamylcysteine synthetase deficiency disorder had spinocerebellar degeneration. Individuals suffering from this condition are generally clumsy in their actions, the joints of their body do not function smoothly, pain in joints is a common complaint in these individuals that leads to uncoordinated movements, they have difficulty in walking, and tremor is also very commonly associated with this condition. These individuals have problems performing precise activities such as writing and painting due to tremors in their hands and other body parts.
-
Peripheral Neuropathy: It is caused due to damage in peripheral nerves (nerves present outside the brain). Patients suffering from peripheral neuropathy have symptoms of numbness and weakness in the hands and legs, leading to difficulty in performing daily basic activities. Patients suffer from sensations like pin or needle pricking in the hands and legs. Sometimes painful sensations are also reported in such cases.
-
Myopathy: This is caused by to lack of proper functioning of the muscle fiber. It most commonly affects the skeletal muscles and leads to muscle stiffness. Muscle stiffness then leads to difficulty in movements. Other than this, features like cramps in muscles and spasms of muscles are also very commonly noted.
Other than the above-mentioned specific medical conditions. Following are a few common features noted in individuals suffering from γ-glutamylcysteine synthetase deficiency disorder:
-
Altered development of speech.
-
Motor skills such as sitting and standing are affected, which causes difficulty in carrying out daily activities.
-
Attention deficit hyperactivity disorder is a commonly noted feature in γ-glutamylcysteine synthetase deficiency disorder. It is a neurodevelopmental disorder diagnosed in childhood and continues up to adulthood. Children suffering from this disorder have difficulty concentrating, get easily distracted, and have delayed thinking abilities. They have difficulty learning the alphabet, spelling, and mathematical tables.
How Is γ-Glutamylcysteine Synthetase Deficiency Disorder Diagnosed?
The diagnostic criteria for this enzyme deficiency genetic disorder can be divided into two categories:
-
Direct: Genetic evaluation by performing specific genetic tests.
-
Indirect: Tests performed to diagnose hemolytic anemia.
Direct tests like genetic mapping help identify the gene associated with γ-glutamylcysteine synthetase deficiency disorder. Moreover, the inheritance pattern can also be studied using genetic tests. Researchers are working specifically on identifying all the genes related to this enzyme deficiency genetic disorder. In indirect methods, hemolytic anemia diagnosis is focused. For this purpose, a complete blood count test is prescribed. Complete blood count tests specify the levels of hemoglobin as well as the red blood cell count. Reduction in hemoglobin count and red blood cell count shows that the individual suffers from anemia. To specify the type of anemia the individual suffers from, tests like bone marrow aspiration and biopsy can be done. Examination under a microscope helps analyze red blood cells' structure, shape, and number. This helps in diagnosing the patient suffering from hemolytic anemia.
Other advanced diagnostic tests used for the diagnosis of γ-glutamylcysteine synthetase deficiency disorder are as follows:
-
Fibroblast culture tests.
-
Polymerase chain reaction test.
Fibroblast culture tests are done to analyze the level of γ-glutamylcysteine synthetase enzyme. The reduced enzyme level in the given fibroblast culture indicates that the individual may suffer from γ-glutamylcysteine synthetase deficiency.
Polymerase chain reaction (PCR) analyzes the sample sequence by sequence and indicates the absence or reduction of theγ-glutamylcysteine synthetase deficiency. Fibroblast culture and polymerase chain reaction tests can be considered specific tests that help detect γ-glutamylcysteine synthetase deficiency disorder early.
Conclusion
Researchers are working to search for a definite treatment protocol for this disorder. The doctors focus on providing symptomatic relief that eases these individuals' daily activities. Psychiatrists aim to reduce the symptoms of behavioral disorders and improve these individuals' socializing skills. Physiotherapists seek to improve the motor skills of these individuals. So that they can sit, stand, and walk without any secondary support or minimum assistance. Dental practitioners aim to improve individuals' oral hygiene to reduce the caries rate. Specialized doctors treat individuals with severe signs and symptoms, including heart and kidney disorders, with utmost care.
