Question

There are a number of mitochondrial disorders that affect people with mutations related to enzymes for the Citric acid cycle, for example:

▪ Fumerase deficiency

▪ Mutations in SUCLA2

▪ Mutations in SUCLG1

▪ Alpha-ketoglutarate dehydrogenase deficiency

o Pick one of these disorders, search the WWW for information on it, and write a paragraph (at least 100 words) in your own words answering the following questions:

▪ What enzyme is affected by the mutation?

▪ Where in the Citric Acid cycle is this enzyme used?

▪ What effect does it have on respiration in the cells?

▪ What symptoms does it produce in the body?

Answer 1

Ans. Fumarase Deficiency

Mutations in the FH gene cause fumarase deficiency. The enzyme, known as fumarase, provides the body with guidelines to help cells use oxygen and build energy. Gene mutations affect the function of the enzyme. The creation of energy in cells during brain development is particularly important; therefore, when the enzyme is inappropriate, the brain is poorly developed leading to many signs and symptoms of fumarase deficiency. The mutation of the FH gene affects the fumarate hydratase enzyme.

The function of fumarase in the citric acid cycle is to catalyze the reversible hydration/dehydration of fumarate to malate and facilitate a transition step in the production of energy in the form of NADH. The fumarate metabolized enzyme in the cytosol is the byproduct of both amino acid catabolism and the urea cycle.

Due to the defect in this fumarase enzyme in the citric acid cycle less energy, is produces ad there is no production of NADH so less energy is yield by cellular respiration which directly affects the growth and development of the organism.

The most common neurological malformations among newborns with fumarase deficiency include poor feeding, poor growth, and poor tone of muscle (hypotonic disease). The infants with this disorder show early starting encephalopathy, seizures, microcephaly, and serious developmental delays (abnormal brain structures or functions). Fumarase deficiency most children do not learn to speak or walk. Some have polycythemia (excess of red blood cells), recurrent vomits, or pancreatitis. A high forehead (frontal bossing), a depressed nasal bridge and broad-spaced eyes are distinctive facial features which may be present. Various types of brain abnormalities may be identified on brain MRI in these patients. These may include thinning or absence of the corpus callosum, enlarged ventricles, an abnormally small brain stem, and cerebral atrophy.

These are the causes, symptoms, and effects of Fumarase Deficiency.