Is Pompe disease an autosomal recessive disorder?

The probability that their children will have the disease is dependent on knowing the genotype of the father. Since his brother died of the disease, we know that his brother was homozgyous recessive. Therefore, their parents must have both been carriers (note that we have to assume that neither of the parents had the disease because they would be unlikely to survive to reproductive age). Usually a cross between two carriers would give offspring in a 1:2:1 ratio of homozyous normal : heterozygous : homozygous recessive. However, since the man doesn't have the disease, we can eliminate the homozygous recessive in the probability equation and so this means that he is either homozygous normal (1/3 chance) or heterozygous carrier (2/3 chance). So the man has a 2/3 chance of being a carrier. If he is a carrier, then the probability that the man would pass on the recessive allele would be 1/2. So, the probability that he is a carrier AND that he would pass on the recessive allele is 2/3 x 1/2 = 2/6 = 1/3. Since his wife is a carrier, then she has a probability of passing on the recessive allele of 1/2. So, the probability that they would have an affected child is the product of both probabilities: 1/3 x 1/2 = 1/6.

Pompe disease has become a public concern nowadays.Without more info about the man you cannot answer the question. Since the man does not have the disease, we know that the man is either heterozygous or homozygous dominant. Just because his brother was homozygous recessive, that does not tell us anything about the man himself. All we know is that both of the man's parents had at least one recessive allele, but they could have had the disease too because it is not necessarily fatal before the person has children (some people can be asymptomatic for their whole lives)

If the man is homozygous dominant, then the children have a 0% chance of getting the disease because they will be 50% homozygous dominant and 50% heterozygous.

If the man is heterozygous, then there is a 25% chance of getting the disease (homozygous recessive), 50% of being heterozygous, and 25% chance of being homozygous dominant.

Pompe disease hits screens in "Extraordinary Measures"

BOSTON (Reuters) - "Extraordinary Measures", starring Harrison Ford and Brendan Fraser, opens on Friday and 101 employees from Genzyme Corp will gather in a Boston movie theater to see themselves portrayed in what some fear may be an unflattering light.

ENTERTAINMENT

The movie chronicles the story of John Crowley, currently the chief executive of Amicus Pharmaceuticals In, in his race to find a cure for Pompe disease, a rare muscle disorder that threatened to kill two of his three children.

For the staff at Cambridge, Massachusetts-based Genzyme, which eventually developed a treatment, the movie has special meaning and opens as the biotechnology company struggles to emerge from its worst year ever.

Last year, a manufacturing crisis caused it to close its Boston-area manufacturing plant after it strained capacity to breaking point. Ironically, it was the company's rush to ramp up production of the Pompe drug, called Myozyme, that led to the crisis.

The movie is loosely based on the book "The Cure" by Wall Street Journal reporter Geeta Anand. It describes the emotional drama of the Crowleys' personal struggle to save their children, and the scientific drama of the drug's development.

"This is our lives played out on screen, and we want to experience it together," said Lori Gorski, a Genzyme spokeswoman.

Pompe disease affects some 5,000 to 10,000 people worldwide, and often kills babies before they reach the age of 2. People with the disease are deficient in an enzyme known as acid alpha-glucosidase, which is responsible for breaking down glycogen, a form of sugar stored in muscle cells. When glycogen builds up in these cells it can cause swelling of the heart and other organs and lead to disability and death.

SCIENTIFIC BATTLE

The race for a cure was fought out among scientists at four companies, including Genzyme. Between 1998 and 2002, Genzyme teamed up with a trio of companies and acquired rights to their experimental drugs.

The company's first partnership was with Pharming Group NV, a company based in the Netherlands that was developing an enzyme using milk from hundreds of transgenic rabbits.

Genzyme also partnered with a research group from Duke University that was using cells taken from Chinese hamster ovaries. In 2001 it acquired Novazyme, a company that John Crowley -- played by Brendan Fraser in the movie -- helped form based on the work of Dr. William Canfield, the scientist who is played by Harrison Ford. Genzyme also had its own product.

Finally, Genzyme chief executive Henri Termeer demanded that his researchers stop bickering.

"How many more babies have to die?" he shouted from the balcony of the company's boardroom.

In late November 2001, Genzyme decided to run an experiment to figure out which program to focus on.

A review of the data revealed Genzyme's product was the most efficacious and the easiest to manufacture. The other programs were discontinued and in 2006, Myozyme was approved in the United States and Europe.

But the Pompe story was far from over.

The U.S. Food and Drug Administration still has not approved a scaled-up version of the drug, which will be known in the United States as Lumizyme. That means there is still not enough of the commercial product to go around.

Gorski thinks some employees might be hurt at the way Genzyme (called Zymagen in the film) is portrayed -- as a somewhat cold bureaucracy -- and said the real story is far more dramatic than any movie.

"Putting 20 years of work into 90 minutes is a hard task that can never be put on screen," she said.

(Reporting by Toni Clarke, editing by Maureen Bavdek)

Pompe Disease - Introduction

Pompe disease is described as a progressive sickness because it gets worse over time. The progressive nature of Pompe disease is a result of its fundamental cause: the continuing buildup of a substance called glycogen inside muscle cells. As overload glycogen continues to build up, it interferes with normal cell function and causes continuous damage to cells, ensuing in deterioration muscle weakness that can affect movement, breathing, and, in infants, heart function.

Pompe Disease is a neuromuscular, autosomal recessive metabolic disorder in the family of lysosomal storage diseases caused by a deficiency in the enzyme Acid alpha-glucosidase , which is needed to break down glycogen—a long, branched glucose polymer and stored form of sugar used for energy. It is the only glycogen storage disease with a defect in lysosomal metabolism and was the first glycogen storage disease to be identified, in 1932.

The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.

The disease is named after Johann Pompe, who characterized it in 1932.[1][2]
Despite Pompe's initial observations, the metabolic basis for the disease remained a puzzle until Christian de Duve's discovery of lysosomes in 1955, leading his co-worker Henri G. Hers to establish the principle of lysosomal storage diseases, in 1965.