Pompe disease is due to a deficiency in lysosomal α-1,4-glucosidase, also called acid maltase. Lysosomes function as recycling centers in the cell and normally degrade excess muscle glycogen into glucose for the energy-converting reactions of the glycolytic pathway. Pompe disease was described in 1932 by Dutch pathologist Johann Pompe, who recognized that lysosomes in the affected patient's accumulated large amounts of glycogen. However, Henri Hers—the same Belgian pathologist who described the symptoms of liver glycogen phosphorylase deficiency (Hers disease)—discovered in 1965 that Pompe disease was due to a lysosomal α-1,4-glucosidase deficiency.Enzyme deficiencyDisease nameOrganDisease symptomsLysosomal α-1,4- glucosidasePompeAll organsHeart failure in infantile form; muscle defects in juvenile form Answer these questions: What protein/enzyme does the mutation effects? Symptoms and, if you can, how are the symptoms connected to the mutation. Why does the mutation cause these symptoms?prognosistreatment optionsIncidence. Are there populations where incidence is more prevalent?Go to a literature and find one current reference that describes some aspect of research being done on the condition and the significance of the research (current means in the last 5 years). The treatments for most of these glycogen storagediseases depend on the severity of the symptoms and are ofonly moderate success in many cases. In the case of Pompedisease, however, it is now possible to use enzymereplacement therapy to treat these patients, which involvesweekly infusions with recombinant lysosomal a-1,4-glucosidase protein. Although infusion of this recombinantenzyme does not cure the disease, studies have shown that itcan slow the progression of disease symptoms in patientswith juvenile and adult-onset Pompe disease. Figure 14.47shows muscle biopsies from a Pompe disease patient whohad been treated weekly with recombinant lysosomal a-1,4-glucosidase protein for 1 year. In this particular case, thepatient showed a remarkable decrease in the amount ofaccumulated glycogen. William Canfield, a glycobiologist,and John Crowley, a biotechnology entrepreneur, workedtogether at their start-up company Novazyme to develop aclinical protocol to treat Pompe disease using enzymereplacement therapy. Although an improved treatment forPompe disease was later developed using a differentpreparation of a-1,4-glucosidase than that pioneered byCanfield and Crowley, the efforts of Canfield and Crowleydemonstrated that protein-based drugs, also called biologics,could be used to treat human disease. Excess lysosomal glycogen is present beforetreatmentGlycogen is reduced after treatment witha-1,4-glucosidaseFigure 14.47 Enzyme replacement therapy usingrecombinant lysosomal a-1,4-glucosidase protein hasbeen used successfully to treat Pompe disease. Musclebiopsies of a Pompe disease patient before and after 52weeks of treatment are shown. The darkly stainedmaterial in the left panel is excess glycogen in lysosomalcompartments, which was present prior to enzymereplacement therapy. REPRODUCED WITH PERMISSION OFTHE AUTHOR. B. L. THURBERG ET AL. (2006).CHARACTERIZATION OF PRE- AND POST-TREATMENTPATHOLOGY AFTER ENZYME REPLACEMENT THERAPY FORPOMPE DISEASE. LABORATORY INVESTIGATION, 86, 1208-1220.DOI:10.1038/LABINVEST.3700484; PUBLISHED ONLINE 30 OCTOBE2006.

Pompe disease is due to a deficiency in lysosomal α-1,4-glucosidase, also called acid maltase. Lysosomes function as recycling centers in the cell and normally degrade excess muscle glycogen into glucose for the energy-converting reactions of the glycolytic pathway. Pompe disease was described in 1932 by Dutch pathologist Johann Pompe, who recognized that lysosomes in the affected patient's accumulated large amounts of glycogen. However, Henri Hers—the same Belgian pathologist who described the symptoms of liver glycogen phosphorylase deficiency (Hers disease)—discovered in 1965 that Pompe disease was due to a lysosomal α-1,4-glucosidase deficiency. Enzyme deficiency Disease name Organ Disease symptoms Lysosomal α-1,4- glucosidase Pompe All organs Heart failure in infantile form; muscle defects in juvenile form Answer these questions: What protein/enzyme does the mutation effects? Symptoms and, if you can, how are the symptoms connected to the mutation. Why does the mutation cause these symptoms? prognosis treatment options Incidence. Are there populations where incidence is more prevalent? Go to a literature and find one current reference that describes some aspect of research being done on the condition and the significance of the research (current means in the last 5 years).

Biochemistry

9th Edition

ISBN:9781319114671

Author:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Publisher:Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.

Chapter1: Biochemistry: An Evolving Science

Section: Chapter Questions

Problem 1P

See similar textbooks

Related questions

Question

Pompe disease is due to a deficiency in lysosomal α-1,4-glucosidase, also called acid maltase. Lysosomes function as recycling centers in the cell and normally degrade excess muscle glycogen into glucose for the energy-converting reactions of the glycolytic pathway. Pompe disease was described in 1932 by Dutch pathologist Johann Pompe, who recognized that lysosomes in the affected patient's accumulated large amounts of glycogen. However, Henri Hers—the same Belgian pathologist who described the symptoms of liver glycogen phosphorylase deficiency (Hers disease)—discovered in 1965 that Pompe disease was due to a lysosomal α-1,4-glucosidase deficiency.

Enzyme deficiency	Disease name	Organ	Disease symptoms
Lysosomal α-1,4- glucosidase	Pompe	All organs	Heart failure in infantile form; muscle defects in juvenile form

Answer these questions:
What protein/enzyme does the mutation effects?
Symptoms and, if you can, how are the symptoms connected to the mutation. Why does the mutation cause these symptoms?
prognosis
treatment options
Incidence. Are there populations where incidence is more prevalent?
Go to a literature and find one current reference that describes some aspect of research being done on the condition
and the significance of the research (current means in the last 5 years).

The treatments for most of these glycogen storage
diseases depend on the severity of the symptoms and are of
only moderate success in many cases. In the case of Pompe
disease, however, it is now possible to use enzyme
replacement therapy to treat these patients, which involves
weekly infusions with recombinant lysosomal a-1,4-
glucosidase protein. Although infusion of this recombinant
enzyme does not cure the disease, studies have shown that it
can slow the progression of disease symptoms in patients
with juvenile and adult-onset Pompe disease. Figure 14.47
shows muscle biopsies from a Pompe disease patient who
had been treated weekly with recombinant lysosomal a-1,4-
glucosidase protein for 1 year. In this particular case, the
patient showed a remarkable decrease in the amount of
accumulated glycogen. William Canfield, a glycobiologist,
and John Crowley, a biotechnology entrepreneur, worked
together at their start-up company Novazyme to develop a
clinical protocol to treat Pompe disease using enzyme
replacement therapy. Although an improved treatment for
Pompe disease was later developed using a different
preparation of a-1,4-glucosidase than that pioneered by
Canfield and Crowley, the efforts of Canfield and Crowley
demonstrated that protein-based drugs, also called biologics,
could be used to treat human disease.

Excess lysosomal glycogen is present before
treatment
Glycogen is reduced after treatment with
a-1,4-glucosidase
Figure 14.47 Enzyme replacement therapy using
recombinant lysosomal a-1,4-glucosidase protein has
been used successfully to treat Pompe disease. Muscle
biopsies of a Pompe disease patient before and after 52
weeks of treatment are shown. The darkly stained
material in the left panel is excess glycogen in lysosomal
compartments, which was present prior to enzyme
replacement therapy. REPRODUCED WITH PERMISSION OF
THE AUTHOR. B. L. THURBERG ET AL. (2006).
CHARACTERIZATION OF PRE- AND POST-TREATMENT
PATHOLOGY AFTER ENZYME REPLACEMENT THERAPY FOR
POMPE DISEASE. LABORATORY INVESTIGATION, 86, 1208-1220.
DOI:10.1038/LABINVEST.3700484; PUBLISHED ONLINE 30 OCTOBE
2006.

Expert Solution

Step 1

Pompe disease was named after Johann Pompe who identified the disease in 1932. It is a lysosomal storage disorder. Here, lysosomal enzyme α-1,4- glucosidase is mutated or absent. This disease results in swelling of glycogen-filled lysosomes in many tissues.

Since you have posted a question with multiple sub parts, we will provide the solution only to the first three sub parts as per our Q&A guidelines. Please repost the remaining sub parts separately.

Trending now

This is a popular solution!

Step by step

Solved in 4 steps

SEE SOLUTION Check out a sample Q&A here