Question

Fabry Disease

A 35-year-old man has a history of chronic burning pain in his hands and feet since early childhood. His family history is significant for two maternal uncles who died in their 40’s of renal failure. His mother had a stroke in her 50’s, but is still living. He has just learned that he has Fabry disease and is at very high risk for renal failure, early onset heart disease and stroke. He remembers being told about a enzyme replacement therapy but was too overwhelmed at that time to now recall what he was told. He also wants to know if there are any other options. The scenario described is typical for the presentation of the classical form. There is a less severe variant referred to as the cardiac variant because it is not associated with renal failure.

1. What gene is mutated in Fabry disease and where in the genome is the gene located?
2. Identify the enzyme altered by this mutation and discuss the consequences that result from the impairment of this enzyme.
3. What is the pattern of inheritance for Fabry disease?
4. Discuss some potential therapies, including the enzyme replacement therapies mentioned, as well as any additional options that there may be for this patient.

Answer 1

1. What gene is mutated in Fabry disease and where in the genome is the gene located?

Fabry disease is a rare genetic disorder its an X linkend diseases which means the mutated gene is present on the X chromosome.The gene mutated in thus Fabry disease is GLA gene and the function of this gene is to produce an enzyme called Alpha galactosidase A which are actively present in Lysosomes of the cells.The decrease in the amount of Alpha galactosidase A enzyme will cause bulid up of globotriaosylceramide a fat in the whole body because one of the function of this enzyme is to break down globotriaosylceramide fat which is made of three sugars attached to fatty acids.

2. Identify the enzyme altered by this mutation and discuss the consequences that result from the impairment of this enzyme?

The enzyme altered by this mutation is Alpha galactosidase A enzyme which is present in the lysosomes which are known as the repairing part of the cells or the suicidal bags.The mutation of GLA gene here causes deficiency in Alpha galactosidase A enzyme.

The decrease in the amount of Alpha galactosidase A enzyme will cause bulid up of globotriaosylceramide a fat in the whole body because one of the function of this enzyme is to break down globotriaosylceramide fat which is made of three sugars attached to fatty acids.

Thus accumulation of the fat or globotriaosylceramide occurs in all parts of the body mostly the bood vessels and causes blocks and cardiac areest and strike and alao these get accumulated in cells in the kidneys, heart, and nervous system. The progressive accumulation of globotriaosylceramide damages these cells, leading to the varied signs and symptoms of Fabry disease.

3. What is the pattern of inheritance for Fabry disease?

Fabry disease is an X linked disease which means the gene mutation occurs in the X chromosomes. Males are mostly affected by this mutation as they contain XY chromosomes one altered copy of GLA gene in each cell is sufficient to cause the disease but in femalesas they contains XX chromosomes alteration in one cell wont make much severe symptoms and  most of them act as carriers and may not have severe symptoms and in rare cases no symptoms too.
But a female who delevop symptoms can even some times make it severe upto development of renal failure,cardiac arrest and even stroke too.

4.Discuss some potential therapies, including the enzyme replacement therapies mentioned, as well as any additional options that there may be for this patient.?

The treatment always aims at treating underlying condition of deficiency of the enzyme and preventing the organ damage .Thus enzyme replacement therapy place a major role as a part of treatment and for other organs damaged the care depends according to the damage of particular organ affected.

ENZYME THERAPY

Certain country like Europe ,US etc have manufactured Alpha galactosidase A enzyme by changing its bond type so that they are not destroyed by the mutated gene and is used as enzyme therapy ,even though its not a cure but it could prevent the severity.

ORGAN SPECIFIC TREATMENT

It depends according to the organ affected by the Fabry disease.Enzyme replacement therapy reduces the lain felt by the patient but even though some patients needs analgesics therapy and NS AIDS and in case of Renal failure they needs Hemodialysis and in cardiac complications caused such as abnormal heart rhythms, which may require a pacemaker or implantable defibrillator, while the restrictive cardiomyopathy often seen may require diuretics. So,here symptomatic treatment is given avvording to area affected.

GENE THERAPY

Its still under clinical trials and yet to be practiced clinically. And there are even lot many drugs under studies expecting for a great hope for the condition.