eMedicine Specialties > Physical Medicine and Rehabilitation > Myopathy

Acid Maltase Deficiency Myopathy: Treatment & Medication

Author: Michael Weinik, DO, Associate Chairman, Associate Professor, Physical Medicine and Rehabilitation, Temple University Hospital
Coauthor(s): Frank J King, MD, Clinical Instructor, Department of Physical Medicine and Rehabilitation, Georgia Pain Physicians/Emory School of Medicine
Contributor Information and Disclosures

Updated: Apr 15, 2009

Treatment

Rehabilitation Program

Physical Therapy

Little information has been published regarding the physiatric management of Pompe disease, probably owing to the lack of a specific treatment, the relentlessly progressive course, and the fatal outcome of the disease.

In the juvenile and adult forms of acid maltase deficiency (AMD), it would seem intuitive to focus physiatric treatment on the systems involved.

The use of assistive devices and orthoses may prove beneficial in patients with AMD who develop ambulatory difficulties. The use of intermittent positive pressure ventilation in Pompe disease would seem appropriate; however, because the disease is limited not only to the respiratory muscles but also involves the heart, the final outcome is likely to be the same.

Medication

Treatment for this fatal disorder is limited. A copious amount of research into acid maltase deficiency (AMD) is exploring the possibility of replacing the deficient enzyme by means of gene therapy. Up to this point, the results have been frustratingly unfruitful. Future strategies may include in-vivo or ex-vivo gene therapy and/or mesenchymal stem cell or bone marrow transplantation approaches. Some results have been positive in animal models, but to extrapolate these results to the human form, new approaches to AMD must be determined and improvements in the access to cardiac and skeletal muscle must be made. Newer, more efficacious and innocuous vectors also must be discovered. L-alanine supplementation in late-onset AMD has been shown to decrease resting energy expenditure.

Emerging research has shown that infusions of recombinant human alpha-glucosidase from rabbit milk is helpful for stabilizing pulmonary function and improving muscle fatigue in early onset and late-onset Pompe disease. The younger and least affected children have shown the most improvement and delay in the progression of the disease process.

Originally described in the treatment of mice with glycogen storage disease, Ven den Hout et al, in an open-label study, treated 4 babies with recombinant human alpha-glucosidase obtained from rabbit milk.10 Recombinant glucosidase was administered intravenously at a weekly dose of 15-20 mg/kg and later was increased to 40 mg/kg. Alpha-glucosidase activity normalized in muscle, the tissue morphology and motor and cardiac function improved, and the left ventricular mass index significantly decreased. Normal neurologic development was noted in all patients. Subsequent studies have involved the use of recombinant human alpha-glucosidase derived from Chinese hamster ovary cells.2,11

In a 2009 open-label, multicenter study, Nicolino et al employed intravenous treatment with recombinant human alpha-glucosidase in 21 patients, aged 3-43 months, with advanced Pompe disease.12 The drug was administered every 2 weeks for up to 168 weeks; the investigators found that, compared with an untreated reference cohort, the risk of death in the treated children was reduced by 79% (P <0.001), and the risk that invasive ventilation would be required was decreased by 58% (P = 0.02).

The lessons learned from research into AMD may lead to better understanding and treatment of other genetic disorders.13

Enzyme replacement

Used as replacement therapy. Recombinant human enzyme alpha-glucosidase has recently been designated an orphan drug.


Alglucosidase alfa (Myozyme)

Recombinant human enzyme alpha-glucosidase (rhGAA) indicated as an orphan drug for treatment of Pompe disease. Replaces rhGAA, which is deficient or lacking in persons with Pompe disease. Alpha-glucosidase is essential for normal muscle development and function. Binds to mannose-6-phosphate receptors and then is transported into lysosomes; undergoes proteolytic cleavage that results in increased enzymatic activity and ability to cleave glycogen. Improves infant survival without requiring invasive ventilatory support compared with historical controls without treatment.

Adult

Data limited; administer as in pediatrics

Pediatric

20 mg/kg IV q2wk; initial infusion rate not to exceed 1 mg/kg/h; may increase infusion rate by 2 mg/kg/h q30min to a maximum of 7 mg/kg/h if tolerated

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Serious adverse effects reported include heart and lung failure; infusion-related reactions are common (51%) and include life-threatening anaphylaxis, shock, or respiratory or cardiac events (eg, bronchospasm, dyspnea, arrhythmias, hypotension, hypertension); medical support measures must be readily available; discontinue or temporarily stop infusion if reaction occurs; common adverse effects include pneumonia, respiratory failure and distress, infection, and fever

More on Acid Maltase Deficiency Myopathy

Overview: Acid Maltase Deficiency Myopathy
Differential Diagnoses & Workup: Acid Maltase Deficiency Myopathy
Treatment & Medication: Acid Maltase Deficiency Myopathy
Follow-up: Acid Maltase Deficiency Myopathy
Multimedia: Acid Maltase Deficiency Myopathy
References
Further Reading
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References

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Keywords

Pompe disease, Pompe's disease, Pompe, glycogen storage disease, myopathy, cardiomegaly, maltase, acid maltase, acid maltase deficiency, Myozyme, glycogenosis, cardiomegalia glycogenica diffusa, type II glycogenosis, glycogen storage disease type II, severe muscle weakness

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Contributor Information and Disclosures

Author

Michael Weinik, DO, Associate Chairman, Associate Professor, Physical Medicine and Rehabilitation, Temple University Hospital
Michael Weinik, DO is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation
Disclosure: Nothing to disclose.

Coauthor(s)

Frank J King, MD, Clinical Instructor, Department of Physical Medicine and Rehabilitation, Georgia Pain Physicians/Emory School of Medicine
Frank J King, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, and Association of Academic Physiatrists
Disclosure: Nothing to disclose.

Medical Editor

Elizabeth A Moberg-Wolff, MD, Associate Professor and Pediatric PM&R Fellowship Director, Department of Physical Medicine and Rehabilitation, Medical College of Wisconsin; Program Director, Tone Management and Mobility, Department of Physical Medicine and Rehabilitation, Children's Hospital of Wisconsin
Elizabeth A Moberg-Wolff, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation
Disclosure: Medtronic Neurological Grant/research funds Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kat Kolaski, MD, Assistant Professor, Departments of Orthopedic Surgery and Pediatrics, Wake Forest University School of Medicine
Kat Kolaski, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation
Disclosure: Nothing to disclose.

CME Editor

Kelly L Allen, MD, Regional Medical Director, IMX-Medical Management Services
Disclosure: Nothing to disclose.

Chief Editor

Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers
Denise I Campagnolo, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, Association of Academic Physiatrists, and Consortium of Multiple Sclerosis Centers
Disclosure: Teva Neuroscience Honoraria Speaking and teaching; Serono-Pfizer Honoraria Speaking and teaching

 
 
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