About acid maltase deficiency

What is acid maltase deficiency?

Pompe disease is a rare multisystem genetic disorder that is characterized by absence or deficiency of the lysosomal enzyme alpha-glucosidase (GAA). This enzyme is required to breakdown (metabolize) the complex carbohydrate glycogen and convert it into the simple sugar glucose. Glycogen is a thick, sticky substance and failure to properly break it down results in massive accumulation of lysosomal glycogen in cells, particularly in cardiac, smooth, and skeletal muscle cells. Pompe disease is a single disease continuum with variable rates of disease progression and different ages of onset. The infantile form is characterized by severe muscle weakness and abnormally diminished muscle tone (hypotonia) without muscle wasting, and usually manifests within the first few months of life. Additional abnormalities may include enlargement of the heart (cardiomegaly), the liver (hepatomegaly), and/or the tongue (macroglossia). Without treatment, progressive cardiac failure usually causes life-threatening complications by the age of 12 to 18 months. Pompe disease can also present in childhood, adolescence or adulthood, collectively known as late-onset Pompe disease. The extent of organ involvement may vary among affected individuals; however, skeletal muscle weakness is usually present with minimal cardiac involvement. Initial symptoms of late-onset Pompe disease may be subtle and may go unrecognized for years. Pompe disease is caused by mutations of the GAA gene and is inherited as an autosomal recessive trait.

Pompe disease belongs to a group of diseases known as the lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that function as the primary digestive units of cells. Enzymes within the lysosomes break down or digest particular nutrients, such as complex molecules composed of a sugar attached to a protein (glycoproteins). There are more than 40 different lysosomal enzymes. Low levels or inactivity of the GAA lysosomal enzyme leads to the accumulation of glycogen in the lysosomes of various cells within the body with unwanted consequences. Pompe disease may also be classified as a glycogen storage disease, a group of metabolic disorders characterized by abnormalities involving the use and/or storage of glycogen.

What are the symptoms for acid maltase deficiency?

Soft murmur symptom was found in the acid maltase deficiency condition

Patients with the ‘classic infantile’ form of Pompe disease are the most severely affected. Although hardly any symptoms may be apparent at birth, the disease usually presents within the first three months of life with rapidly progressive muscle Weakness (‘floppy infants’), diminished muscle tone (hypotonia), respiratory deficiency, and a type of heart disease known as hypertrophic cardiomyopathy, a condition characterized by abnormal thickening of the walls of the heart (mainly the left chamber and the wall between the left and right chamber) resulting in diminished cardiac function. These problems together culminate in cardio-respiratory failure within the first 2 years of life.

Many infants have a large, protruding, tongue and a moderate enlargement of the liver. The legs often rest in a frog position and feel firm on palpation (pseudo-hypertrophy). Feeding and swallowing problems as well as respiratory difficulties, which are often combined with respiratory tract infections, are common. Major developmental milestones such as rolling over, sitting up, and standing are delayed or not achieved. Mental development is usually normal. Virtually all infants experience hearing loss. The ‘classic infantile’ form of Pompe disease is caused by a total absence of acid alpha-glucosidase (GAA) activity and by a rapid buildup of glycogen in skeletal muscle and heart.

‘Childhood’ Pompe disease typically presents during childhood, and ‘adult’ Pompe disease during adulthood. In the current literature, these two forms of Pompe disease are often grouped together as ‘late-onset’ Pompe disease (abbreviated as LOPD) despite the fact that the time of presentation can vary from the first year of life to the eighth decade. Patients who develop symptoms early in life tend to be more severely affected and to have a faster rate of disease progression than those who develop symptoms later in life. Both children as well as adults usually have more GAA activity (their GAA deficiency is not total) than the most severely affected infants (who do not have any GAA activity), and the glycogen buildup is usually not as rapid. However, symptoms do progress, and can greatly affect the quality of life and diminish the lifespan.

Childhood and adult Pompe disease are associated with progressive Weakness of mainly the proximal muscles (limb girdle, upper arms and upper legs), and varying degrees of respiratory Weakness due to dysfunction of the diaphragm and the intercostal muscles (muscles between the ribs). The lower limbs are more affected than the upper limbs. The extent of muscle involvement is highly variable. Balance can be affected as the major leg muscles lose their strength and spring, forcing core muscles to take up the slack to maintain an upright posture. The muscles adjacent to the spinal column (para-spinal muscles) and neck are usually also involved. Weakness of the para-spinal muscles around puberty can cause abnormal curvature of the spine (scoliosis). Due to the combination of these serious symptoms, affected individuals may become wheelchair and/or ventilator dependent.

Other symptoms can include chewing and swallowing difficulties and drooping of the upper eyelids (ptosis). Additionally, blood vessel abnormalities due to smooth muscle Weakness and problems of the urinary and digestive systems have been reported.

What are the causes for acid maltase deficiency?

Pompe disease is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease. Pompe disease carriers will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

Pompe disease is caused by pathogenic variations (mutations) in the acid alpha-glucosidase (GAA) gene. Close to 600 different GAA gene variations have been identified in families with this disorder. All the known variations of the GAA gene are collected and listed in the Pompe variant database at: www.pompevariantdatabase.nl along with a description of how detrimental they are and with which clinical forms of Pompe disease they are associated.

The degree of acid alpha-glucosidase (GAA) deficiency is dictated by the nature of the variations in each of the 2 GAA gene copies (1 from the father with variation A and 1 from the mother with variation B) and their combined effect. Generally: the more GAA deficiency these variants are causing, the earlier the onset of symptoms, the faster the disease progression, and the greater the clinical severity. However, the clinical presentation of Pompe disease is not solely dictated by the nature of the inherited pathogenic variations in the 2 GAA gene copies, but additionally influenced by a number of still unknown genetic, epigenetic, and environmental factors. These latter might include diet, lifestyle, exercise, etc.

What are the treatments for acid maltase deficiency?

The treatment of Pompe disease is disease-specific, symptomatic and supportive. Treatment requires the coordinated efforts of a team of specialists. The input of pediatricians, internists, neurologists, orthopedists, cardiologists, dieticians, physical therapists and other healthcare professionals may be needed to develop the treatment plan. The treatment plan must be patient centered, including the patient’s self-descriptions or caregiver’s descriptions (patient history), which provide important data for the team of specialists. A patient or caregiver who is fully informed can provide better experiential data. Genetic counseling is of crucial importance for affected individuals and their families.

Enzyme Replacement Therapy Enzyme replacement therapy (ERT) is an approved treatment for all patients with Pompe disease. It involves the intravenous administration of recombinant human acid alpha-glucosidase (rhGAA). This treatment is called Lumizyme (marketed as Myozyme outside the United States) and was first approved by the U.S. Food and Drug Administration (FDA) in 2006. ERT has been shown to extend the life expectancy of patients with infantile-onset Pompe disease, but these patients are not fully cured and residual symptoms remain. There is some evidence that the currently prescribed and approved dosage is not sufficient in all patients.

Most patients with childhood and adult forms of Pompe disease also benefit from ERT. In 2021, avalglucosidase alfa-ngpt (Nexviazyme) was approved by the FDA to treat patients one year of age and older with late-onset Pompe disease. This enzyme replacement therapy is an intravenous medication that helps reduce the accumulation of glycogen.

Supportive Therapies Additional treatment of Pompe disease is symptomatic and supportive. Respiratory support may be required, as most patients have some degree of respiratory compromise and/or respiratory failure. Physical therapy may be helpful to strengthen respiratory muscles. Some patients may need respiratory assistance through mechanical ventilation (i.e. Bipap or volume ventilators) during the night and/or periods of the day or during respiratory tract infections. Mechanical ventilation support can be through noninvasive or invasive techniques. Decisions about the duration of respiratory support are best made by the patients themselves or the parents in careful consultation with the patient’s physicians and other members of the healthcare team. Physiotherapy is recommended to improve strength and physical ability. Occupational therapy, including the use of canes or walkers, may be necessary. Eventually, some patients may require the use of a wheelchair. Speech therapy can be beneficial in some patients to improve articulation and speech. Orthopedic devices including braces may be recommended in some patients. Surgery may be required for certain orthopedic symptoms such as contractures or spinal deformity.

Since Pompe disease can weaken muscles used for chewing and swallowing, adequate measures may be required to ensure proper nutrition and weight gain. Some patients may need specialized, high-calorie diets and may need to learn techniques to change the size and texture of food to lower the risk of aspiration. Some infants may require the insertion of a feeding tube that is run through the nose, down the esophagus and into the stomach (nasogastric tube). In some children, a feeding tube may need to be inserted directly into the stomach through a small surgical opening in the abdominal wall. Some individuals with childhood or adult Pompe disease / LOPD may require a soft diet, but few require feeding tubes.

What are the risk factors for acid maltase deficiency?

Acid Maltase Deficiency is basically a metabolic muscle disease. Acid maltase deficiency is a metabolic muscle disorder, a group of diseases that interferes with the processing of food (in this case, carbohydrates) for energy production.

  • Acid maltase deficiency results from a defect in the gene for the acid maltase enzyme that prevents the breakdown of glycogen (stored sugar).
  • In adults, this deficiency is associated with progressive muscle disorder and may affect respiratory muscles causing respiratory failure.
  • In a recessive genetic disorder, both copies of a certain gene need to be defective for the condition to manifest itself. It has been shown that mutations in the acid alpha-glucosidase gene may cause AMD.
  • People who only have one mutated gene are called carriers.If only one parent is a carrier, none of the children will have AMD, but 50% of the children will also be carriers; if both parents are carriers, then there is a 50% chance that a child will be a carrier and a 25% chance that a child will have AMD.
  • Flu shots or other viral vaccines may help reduce the risk of infection in the lungs.

Massive cardiomegaly,Soft murmur,Heart failure
Weak muscles,Poor muscle tone,Enlarged liver,Failure to gain weight and grow at the expected rate (failure to thrive),Trouble breathing,Feeding problems,Infections in the respiratory system,Problems with hearing

Is there a cure/medications for acid maltase deficiency?

There a cure/medications for acid maltase deficiency. These include:

  • Feeding tube: Some infants with AMD have difficulty feeding, so tube feeding may be used to deliver nutrients.
  • Ventilators: Because many patients with acid maltase deficiency (AMD) develop respiratory problems, a mechanical ventilator may be recommended by a doctor to assist with breathing.
  • Viral medications: Flu shots or other viral vaccines may help reduce the risk of infection in the lungs.
  • Assistive devices: Devices, such as leg braces, walkers, or wheelchairs, may be used to help patients with weakened muscles who have difficulty walking.
  • Enzyme therapy: An enzyme replacement therapy called Myozyme has been approved to treat AMD. Myozyme is a recombinant form of alpha-glucosidase, which can provide
  • Myozyme requires a prescription, and is recommended at a dosage of 20 milligrams/kilogram body weight, administered every two weeks by injection.
  • A number of side effects have been observed in patients taking Myozyme, including an irregular heartbeat, swelling at the injection site, headache and dizziness, swelling of the hands or feet, and a severe allergic reaction (involving rash, hives, difficulty breathing, and tightness in the chest).
  • Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of acid maltase deficiency.

Massive cardiomegaly,Soft murmur,Heart failure
Weak muscles,Poor muscle tone,Enlarged liver,Failure to gain weight and grow at the expected rate (failure to thrive),Trouble breathing,Feeding problems,Infections in the respiratory system,Problems with hearing

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