Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, only females pass mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children. In most cases, people with MELAS inherit an altered mitochondrial gene from their mother. Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MELAS. Diagnosis
MRI: Multifocal infarct-like cortical areas in different stages of ischemic evolution, areas that do not conform to any known vascular territory. Initial lesions often occur in the occipital or parietal lobes with eventual involvement of the cerebellum, cerebral cortex, basal ganglia, and thalamus.Lactate levels are often elevated in serum and cerebrospinal fluid. MR spectroscopy may show an elevated lactate peak in affected and even unaffected brain areas. Muscle biopsy shows ragged red fibers. However, genetic evaluation should be done first, which eliminates the need for muscle biopsy in most cases. Diagnosis may be molecular or clinical:
Stroke-like episodes before or after 40 years old
Encephalopathy with seizures or dementia
Blood lactic acidosis* or ragged red fibers on muscle biopsyDue to mitochondrial heteroplasmy, urine and blood testing is preferable to blood alone. PCR and ARMS-PCR are commonly used, reliable, rapid, and cost-effective techniques for the diagnosis of MELAS.Hearing loss and mitochondrial diabetes are common features. Eyes may have a distinctive speckled pigment in the retina, referred to as a maculopathy. Family members may present differently.
Glutathione synthetase deficiency (GSD) is a rare autosomal recessive metabolic disorder that prevents the production of glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. Glutathione also plays a role in processing medications and cancer-causing compounds (carcinogens), and building DNA, proteins, and other important cellular components. Genetics
Mutations in the GSS gene cause glutathione synthetase deficiency. This gene provides instructions for making the enzyme glutathione synthetase. This enzyme is involved in a process called the gamma-glutamyl cycle, which takes place in most of the bodys cells. This cycle is necessary for producing a molecule called glutathione. Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules which are byproducts of energy production. Mutations in the GSS gene prevent cells from making adequate levels of glutathione, leading to the signs and symptoms of glutathione synthetase deficiency. This disorder is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder each carry one copy of the defective gene, but usually are not affected by the disorder. Diagnosis
Glutathione synthetase deficiency can be classified into three types: mild, moderate and severe.