Secondary Logo

Journal Logo

Review

The Emerging Role of the Pediatric Physical Therapist in Evaluation and Intervention for Individuals with Lysosomal Storage Diseases

Haley, Stephen M. PhD, PT; Fragala-Pinkham, Maria MS, PT; Latham, Nancy K. PhD, PT; Skrinar, Alison M. MA, MPH; Cogswell, Deborah MS, PT

Author Information
doi: 10.1097/01.PEP.0000163077.26274.9C
  • Free

INTRODUCTION

Medical and surgical interventions for individuals with lysosomal storage diseases (LSDs) are associated with dramatically improved mortality and morbidity prognoses. Given the promise of new therapies and advances in existing therapies, we believe that this area of pediatric physical therapy (PT) practice is in the midst of change, as individuals who were seen only for maintenance goals in the past may now require active restorative programs. The major objective of this article is to provide a comprehensive update on LSD treatment options that are becoming standards of care and the implications for pediatric physical therapists. We highlight three types of LSDs (Gaucher, mucopolysaccharidoses [MPS] and Pompe) for which treatment is available or will be available in the near future and provide current information about PT management of these disorders.

OVERVIEW

LSDs are a group of more than 40 known genetic disorders caused by an inborn error of metabolism. The genetic defect results in deficiency of a particular enzyme or enzymes within the lysosomes. As a result of the deficiency, substrates that are typically broken down by the enzyme(s) accumulate within the lysosomes and impair cellular function. Individually, LSDs are rare, but as a group are estimated to affect one in 7700 livebirths.1 Diagnosis of an LSD is typically made using biochemical testing following presentation with obvious clinical symptoms and is highly dependent on disease pattern recognition by a clinician. For a definitive diagnosis of a specific LSD, documentation of marked deficiency of enzyme activity levels remains the gold standard. Prenatal diagnosis is available for most LSDs, and newborn screening for LSDs is under development.2 (See Figure 1 for a listing of the most prevalent LSDs.)

Fig. 1.
Fig. 1.:
Distribution of lysosomal storage diseases: shading indicates major types highlighted in article. (Adapted from Meikle et al.1)

The clinical presentation of LSDs varies considerably among the different disorders and even within a particular disorder. Clinical symptoms are progressive, and there are no cures for any known LSD. In the absence of a cure, disease management consists of supportive care and treatment of symptoms and complications. The pathology and typical impairments of individuals with Gaucher, mucopolysaccharidosis (MPS) (types I and II), and Pompe diseases are discussed below. A detailed description of all types of LSDs can be found in a number of sources, including a comprehensive text by Scriver et al3 and articles by Wenger et al4 and Wraith.5 A summary of incidence, pathology, and body systems most affected in selected LSDs is provided in Table 1.

TABLE 1
TABLE 1:
Summary of incidence, etiology, pathology, body system impairments, and inheritance pattern in selected lysosomal storage diseases1,6,8,10,42

Gaucher Disease

Gaucher disease is the most common LSD and is also the most common genetic disease among Ashkenazi Jews.6 The onset of signs and symptoms of Gaucher disease is variable and ranges from infancy to 14 years. There is a broad spectrum of disease severity in Gaucher disease, ranging from type 1 (most common and nonneuronopathic) to type 2, which has an early onset and severe central nervous system involvement and leads to death within the first two years. For individuals with type 3 Gaucher disease, there is a later onset of neurological signs and a more chronic course than in type 2.6

In Gaucher disease, skeletal complications, which include osteopenia, bone infarction, and osteonecrosis, can cause significant functional impairment.7 Individuals with Gaucher disease experience generalized loss of bone mass, and 20% to 40% experience bone crises or acute severe bone pain that appear on bone scans as areas of ischemia.6

Most individuals with type 1 Gaucher disease are ambulatory. Individuals with type 2 Gaucher disease have significantly delayed mobility skills and usually do not develop the ability to ambulate independently. Individuals with Type 3 represent an intermediate clinical severity with functional skills varying from independent household ambulation to independence with wheelchair mobility.6

Mucopolysaccharidosis

MPS consists of a group of disorders caused by a deficiency of the specific lysosomal enzymes needed to break down glycosaminoglycans (GAGs). GAGs are sugar molecules used to build connective tissues and organs in the body. The seven forms of MPS account for roughly 35% of the prevalence of all LSDs.1 This paper focuses on two types of MPS: I and II.

MPS I subtypes have a wide spectrum of clinical involvement: (1) Hurler, the most severe (MPS I-H); (2) Hurler-Scheie, with intermediate clinical severity (MPS I-HS); and (3) Scheie, the least severe (MPS I-S). Individuals with MPS I-H have severe and progressive clinical manifestations, as death due to obstructive airway disease, respiratory infection, or cardiac complications usually occur by age 10 years. Individuals with MPS I-H are usually diagnosed between four and 18 months of age because of their skeletal deformities, recurrent ear and respiratory infections, facial anomalies, and hepatosplenomegaly. Individuals with MPS I-HS, have milder, less progressive physical problems than those with MPS I-H and are usually diagnosed between three and eight years of age. Individuals with MPS I-S have normal cognitive functioning and even milder, less progressive physical problems that those with MPS I-HS. Although MPS I-S patients have can have a normal life span, they may experience corneal clouding, valvular heart disease, and joint stiffness. The constellation of signs and symptoms associated with MPS I syndromes can result in significant functional impairments.8

MPS II, also called Hunter syndrome, includes two forms, one mild and one severe. Signs of the severe form are joint stiffness, mental deterioration, and dwarfing. Hydrocephalus, seizures, obstructive airway disease, cardiac anomalies, hearing and visual impairments, and cognitive delay are the most common clinical manifestations. Death usually occurs by age 15 years in the severe form of MPS II. Individuals with the milder form of Hunter syndrome usually have normal intelligence and milder and less progressive clinical manifestations and live into adult life.8

Individuals with MPS I and II commonly have gait deviations of toe walking, exaggerated hip and knee flexion, decreased trunk rotation, externally rotated hip position, and decreased arm swing. Most young children with MPS I-HS/S and MPS II mild form and children with MPS I-H who have undergone hematopoietic stem cell transplantation usually ambulate without devices. Older children and young adults may need a walker or cane for balance, especially as contractures worsen and their alignment and standing posture are significantly altered. Children with MPS I-H often develop genu valgum due to failure of ossification of the lateral margin of the proximal tibial metaphysis and faster medial growth.9 Depending on the severity of the genu valgum, children with MPS I-H who have undergone a hematopoietic stem cell transplantation and continue to be ambulatory often require surgical intervention.

A buildup of GAGs in the heart valves, blood vessels, trachea, and joints leads to cardiac, respiratory, and musculoskeletal complications resulting in limited functional mobility and endurance. Individuals with MPS who are ambulatory commonly present with decreased gross motor skills and have difficulty participating with their peers during sports activities. Individuals often have difficulty with fine motor activities such as buttoning a shirt, coloring or writing, picking up small objects, and performing other activities that require a fine grasp.

Pompe Disease

Pompe disease is also known as glycogen storage disease type II or acid maltase deficiency. Two clinical phenotypes of Pompe disease have been identified: infantile onset and late onset. While both phenotypes exhibit myopathy, they differ in terms of the age of sign and symptom onset, extent of organ involvement and rate of disease progression.

Infantile-onset Pompe disease (IOPD) is characterized by sign and symptom onset in the first 12 months of life with severe cardiac and skeletal muscle involvement. Death due to cardiorespiratory failure often occurs within the first year of life. Infants present with progressive muscle weakness, hypotonia, cardiomegaly, macroglossia, and associated respiratory and feeding difficulties.10,11 Infants with IOPD typically fail to achieve any major developmental milestones such as independent sitting, standing, and eventually require mechanical ventilation.

In late-onset Pompe disease (LOPD), time of sign and symptom onset ranges from early childhood through late adulthood. Unlike IOPD, cardiac muscle is typically not affected in persons with LOPD. The most common clinical presentation in LOPD is a limb girdle myopathy with progression to respiratory insufficiency over the course of several years. Proximal muscle weakness with truncal involvement is predominant, and there is greater involvement of the lower than the upper limbs. In addition to muscle weakness, individuals with LOPD may complain of fatigue, loss of motor skills, decreased endurance, and low back pain. Lordosis, kyphosis, or scoliosis can occur and may require surgical intervention, especially if onset is in early childhood.11 Children with LOPD often achieve independent ambulation but may eventually lose these skills as the disease progresses.

REVIEW OF MEDICAL INTERVENTIONS AND CLINICAL TRIALS

In the past two decades, new medical approaches to treating LSDs have been introduced into clinical practice, and more are in development.12–14 A summary of clinical trials of medical therapeutics in LSDs is provided in Appendix A. During the development process, the new products proceed through human testing, beginning with phase I and II trials that are usually small, open-label, uncontrolled studies that determine product safety and treatment dose. Phase III trials establish treatment efficacy through multicenter, randomized controlled trials (RCTs) and are usually necessary before a new product is approved for widespread clinical use by a regulatory body, such as the U.S. Food and Drug Administration (FDA).

Currently, the two most commonly used treatments for LSDs are hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). HSCT is any transplantation of blood- or marrow-derived hematopoietic stem cells, regardless of transplant type (ie, allogeneic or autologous) or cell source (ie, bone marrow, peripheral blood, or placental or umbilical cord blood). HSCT is a complex procedure that carries significant risk to the patient. However, if the transplantation is performed early in the course of the disease and the transplant is successfully engrafted, it can dramatically improve survival and other clinical outcomes.15–17 ERTs currently exist for Gaucher, MPS I and II, and Pompe disease. With ERT, the faulty enzyme is replaced through regular (eg, biweekly) intravenous infusions of modified recombinant enzymes. The first ERT for any LSD was approved in 1991 for Gaucher disease. Aglucerase (Ceredase) successfully reduced the accumulated substrates and improved liver function with no serious adverse effects.18 To date, more than 3000 people worldwide with Gaucher disease have been treated with this ERT,12,19 and the treatment has been associated with improved health-related quality of life.20 However, because the enzyme cannot cross the blood-brain barrier, it can only be used to treat the nonneurological manifestations of the disease.14,21 The first ERT for MPS I, laronidase (Aldurazyme), was approved in 2003. Early studies found significant substrate reductions and increases in range of motion.22 During the phase III RCT (n = 45), statistically significant treatment effects were found in walking endurance and forced vital capacity (Aldurazyme [laronidase], BioMarin Pharmaceutical Inc., product description, 2003). An ERT for Pompe disease has been tested in several small, open-label phase I/II trials.23–26 Most of the patients enrolled in these studies had the infantile-onset form of Pompe disease. The studies found a large effect on enzyme activity in the muscle, and cardiac function improved. More importantly, from a PT perspective, improvements in muscle architecture and motor function were seen, particularly in patients who had less severe disease at the start of treatment.27 A phase III multicenter RCT of ERT for Pompe is currently underway. A clinical trial for ERT (iduronate-2-sulfatase) for MPS II is currently in process and has received a fast-tack designation by the FDA.

In the future, more treatment alternatives for LSDs will be available such as substrate inhibition therapy, which reduces substrate buildup and prevents additional accumulation resulting from the enzyme deficiency. The FDA has recently approved the first substrate inhibition therapy for the treatment of Gaucher disease. Another treatment approach is gene therapy.12,13,21 Gene therapy would correct the primary problem in LSDs which is the defect in the patient’s DNA that stops the production of the lysosomal enzymes. However, although progress is being made with animal models, gene therapy is still in an early stage of development, and no protocols in humans are currently in use.4

In summary, medical treatments are now available that improve the prognosis for persons with LSD. These treatments are not a cure, and patients continue to have residual impairments. However, these treatments can halt and sometimes even reverse organ damage, and improvements have been seen in outcomes such as range of motion, aerobic endurance, strength, and pain. The combination of these medical interventions with appropriate PT intervention could facilitate functional gains that were previously impossible for people with LSDs

ADVANCES IN CLINICAL MEASUREMENT

Improved clinical measurement tools are needed to track changes in functional skills as new enzyme replacement therapies and HSCT are coupled with an increased focus on restorative PT management. Although standardized developmental assessments and short endurance tests have been administered to individuals with LSDs in clinical research (Aldurazyme [Laronidase], BioMarin Pharmaceutical Inc. product description, 2003),23 we know of no existing instrument that covers the range of physical, endurance, and functional impairments characteristic of most LSDs. Thus, we highlight two new measurement advances in individuals with LSDs, namely, a revised parent-report functional assessment for Pompe disease and a physical performance test for MPS I.

Physical Performance Measure for MPS I (MPS-PPM)

With the increased use of ERT in persons with MPS I, feasible and responsive instruments are needed to measure functional performance changes. Physical performance testing can provide a more objective assessment than observation or self-report for changes that may be subtle following ERT. As the clinical manifestations of MPS I include reduced joint flexibility,8 with resulting limitations in functional activities, and diminished cardiovascular endurance,22 we developed a physical performance measure (MPS-PPM)28 to examine the extent of physical and functional performance deficits in individuals with MPS I. The MPS-PPM was designed for administration by physical therapists to gain a comprehensive physical performance assessment of limitations in individuals with MPS I. Our clinical experience suggests that individuals with MPS I have difficulty performing arm and leg movements and experience reductions in functional endurance.

We are in the early stages of initial validation of the MPS-PPM, and normative testing is under way. The original MPS-PPM had 14 items and three subtests but has been further revised to improve reliability, responsiveness, and clinical feasibility. On the revised 10-item version, performance items were organized around known areas of weakness and grouped into two subtests: subtest I, Endurance (two items) and Subtest II, Functional Tasks (eight items). Items are described in Appendix B. We believe that the MPS-PPM has potential to be useful in monitoring the natural history of disease progression and the effects of PT intervention.

Pompe-Pediatric Evaluation of Disability Inventory (Pompe-PEDI)

We adapted an existing functional instrument, the PEDI,29 for use with infants, children, and youth with Pompe disease. Since Pompe disease primarily affects motor function,30 we adapted the PEDI self-care and mobility Functional Skills scales. Items were added to the original PEDI to increase the ceiling level, decrease the basal level, and create smaller skill increments between items to improve scoring precision and sensitivity to change. Seventeen new self-care items were added, including feeding, hand function, and basic respiratory skills (eg, blowing out birthday candles and blowing soap bubbles). Fifty-five new mobility items were added in the content areas of head control, floor movement, sitting and transfer, standing (including use of standing equipment), wheelchair mobility, supported ambulation, and advanced gross motor items. All new items retained the original PEDI dichotomous response set of “capable” or “unable.” The Pompe-PEDI31 scale development work resulted in scale expansion and improved precision over the original PEDI.

The Pompe-PEDI has been standardized on a normative sample up through the age of 15 years, and functional reference curves have been developed to describe expected age-based percentiles.32 We have also shown through computer simulations that the mobility and self-care summary and percentile scores can be accurately estimated by computer-adaptive testing methods by using no more than 20 individually tailored items per scale.33 The Pompe-PEDI is currently being applied as a secondary outcome measure in clinical trials of ERT in children with Pompe disease.

PT MANAGEMENT

In this section, PT examination and intervention for individuals with Gaucher, MPS I and II, and Pompe disease are discussed. No studies documenting the efficacy of PT intervention specifically for persons with these disorders are available; therefore, we have used our clinical experience and evidence from other populations to recommend strategies for PT interventions.

Examination

To determine an appropriate intervention plan for a child with an LSD, the physical therapist first completes a comprehensive examination that includes a history (onset of signs and symptoms, progression of the disease, and why the family is seeking services), systems review, and specific tests and measures.34 Because of the progressive nature of these disorders, tests and measures aimed at quantifying a child’s strength, flexibility, endurance, and functional mobility that can be repeated frequently on reexaminations are useful for documenting changes in a child’s abilities. Dosing changes for ERT are influenced by the child’s response as determined by strength, developmental, and functional changes; therefore, it is important for the physical therapist to communicate these findings to specialists involved to keep the overall treatment plan up to date.

Since individuals with LSD often have pulmonary problems, physical therapists also examine alignment and mobility of the rib cage, respiratory muscle activity and strength, positioning of the head and neck, patterns and efficiency of breathing, and use of mechanical assistance. The physical therapist should recognize when a child may need respiratory assistance, discuss with the primary physician, and refer the child for consultation by a pulmonologist. The child may start to use accessory muscles and become short of breath while performing easy activities. For other children, particularly with Pompe disease, shortness of breath may not occur, especially when weakness prevents exertion. Instead, decreased ventilation at night may be the first indication because the natural urge to breathe is lower during sleep and because the abdomen exerts pressure against the diaphragm in prone and supine positions. The most common symptoms of oxygen insufficiency are fatigue, poor sleep, vivid dreams or nightmares, and headaches, especially right after waking.

From information gathered during the PT examination, the therapist identifies problem areas, refers the child to other providers for consultation, and determines the child’s plan of care. Typical clinical characteristics for children with Gaucher disease, MPS, and Pompe disease are summarized in Table 2. Precautions are summarized in Table 3 and should be considered during the initial examination and long-term monitoring plan.

TABLE 2
TABLE 2:
Typical clinical characteristics for individuals with Gaucher, MPS I, II, IV, and Pompe disease
TABLE 3
TABLE 3:
Clinical precautions in selected lysosomal storage diseases6,8,10,42,43

Coordination of Care

Therapists working with a child with LSDs routinely communicate with the child, family, and pediatrician. They also periodically communicate with the orthopedist, neurologist, and/or physiatrist about the child’s therapy program, progress and medical complications. Communication with other team members including the medical specialists (pediatric geneticist, cardiologist, and pulmonologist), counselors (genetic and/or social work), rehabilitation specialists (speech language pathologist, occupational therapist, respiratory therapist, nurse, orthotist, and equipment vendor) and teachers is important. The physical therapist may suggest a referral to a LSD specialist or to a clinical site specializing in LSD treatment regimens.

Service delivery and settings are variable and dependent on the child and family’s needs, disease severity, and treatment regimen. Frequency of PT intervention may be as often as two to three times per week if multiple systems are involved or the child is in a period of rapid development. PT monitoring may be as seldom as monthly or even annually in a specialty clinic, if the child has less involvement, the family has a comprehensive network of support to carry out the intervention program, or the child’s physical status is stable.

On detection of LSD, children may first be referred to early intervention (EI) for PT services. If functional limitations are minimal, the child may not qualify for EI services and may be followed by a physical therapist periodically at an outpatient clinic specializing in the treatment of children with LSDs.

For school-age children with limitations in functional mobility within the school setting, physical therapists often participate in the Individualized Education Plan and assist with setting goals and objectives for the school year. Service delivery may range from consultation to weekly sessions depending on the child’s needs and ability to function in the school setting.

Children with Gaucher disease typically are referred to home or outpatient PT services for assistance with mobility during periods of bone pain. If mobility problems are chronic, then children may receive EI services or school PT to assist them with mobility in the school setting.

For young children with MPS I-H who have received an HSCT, PT services are usually provided in the home setting for the first year because of complications with immunosuppression. A decrease in gross and fine motor skills is often seen after transplantation, and it may take six months for children to regain prior functional skills. Ten months after transplantation, children with MPS I-H continue to gain skills and may gain fine motor skills faster than gross motor skills.35 Following HSCT, the frequency of PT services may increase to two times per week to focus on mobility and fine motor skills. Weekly PT visits may be provided by EI and may also be supplemented by PT services provided through a home health agency.

Individuals with MPS I-S are most often diagnosed between 10 and 20 years of age. Since the onset of signs and symptoms usually occurs during the teenage years, children with MPS I-S may first be referred for PT through the school system if they are experiencing difficulty with functional mobility in that setting as mandated through IDEA Part B.36 Children with MPS I-S may also be seen in an outpatient setting for complaints of joint stiffness and pain and decreased functional mobility.

Child/Family-Related Instruction

For children with Gaucher disease, therapists may advise children to avoid high impact or contact sports such as football, soccer, long distance running, and skiing because of problems with bone lesions. Bike riding, swimming, and walking or hiking are more appropriate activities for children with Gaucher disease.

Information regarding the natural progression of the disease, functional abilities of children and youths with Pompe disease,30 and the medical interventions is expanding at a rapid pace. Therapists can provide children and their families with information about the specific diseases, community resources, and cutting-edge research regarding medical therapeutic options. Contact information for associations that provide information about specific diseases, support groups, national conferences, and current research can be found in Appendix C.

For children with MPS, therapists should provide parents and school personnel with information on signs and symptoms of carpal tunnel syndrome and spinal cord compression and avoidance of activities that exert force or high impact to the neck/head and other joints.

In an advocacy role, therapists should be aware that some pharmaceutical companies offer Expanded Access Programs for certain drug trials. For example, children with Pompe disease who do not meet eligibility criteria to participate in a clinical trial may still be eligible to receive the experimental ERT. Expanded protocols were designed to include the more severely affected patients.

Procedural Interventions.

Gaucher Disease.

For children with Gaucher disease, acute hip lesions can be misdiagnosed as Legg-Calvé-Perthes disease.6 If a child is referred to PT services for management of an orthopedic problem and does not have a specific diagnosis but presents with multiple system involvement, it is important for therapists to recognize this and to communicate concerns to the referring physician. If children with Gaucher disease type 1 are treated early with ERT before they experience organ or bone damage, the signs and symptoms appear to be reversed.

Therapists may provide strength training, functional mobility training with canes or walkers to protect joints and maintain ambulation status, and other equipment recommendations. For types 2 and 3, although improvements in the bones and liver have been reported, ERT has not been as effective on neurological symptoms. For these children, a wheelchair and seating system are usually necessary for mobility.

MPS.

Although significant improvements in functional mobility have been documented following HSCT and ERT, they are not cures for MPS. Individuals with MPS continue to have functional limitations. Physical therapists should assist children in obtaining optimal function through direct PT intervention and/or referral to orthopedic and medical services.

Functional Training.

For young children with MPS I-HS or for children with MPS I-H who receive HSCT, PT intervention may include gait training on level surfaces and stairs, dynamic standing balance training, and transitional movements such as getting in and out of a tub or on and off the floor.

Therapeutic Exercise.

Active exercise and strength training may be helpful to increase strength in the lower and upper extremities. Although no studies of strength training have been reported for children with MPS, there are several studies that have documented the effectiveness of strength training for children who are typically developing.37–39 Researchers have also documented the effectiveness of strength training for children with neuromuscular disorders40 and juvenile rheumatoid arthritis.41 Low resistance and higher repetitions for strength training in children is recommended. For children with neuromuscular disorders, moderate resistance training is recommended at 30% maximum isometric contraction. For children with MPS I and II, a lower training resistance of 20% to 30% maximum isometric contraction or 10 to 15 repetitions maximum is recommended initially because of joint problems and pain. Children often have baseline joint stiffness and pain and may be so weak that they start exercising using their own body weight as resistance and then progress to weights or resistance bands. When doing the strength training exercises, children should be supervised closely so that they use proper technique and avoid injury. A one- to two-day rest between strength training sessions is also recommended along with close monitoring for signs of exercise intolerance, joint pain, or muscle soreness.

Although all joints are usually affected, the shoulders, wrists, fingers, ankles, and hips seem to be most affected. Active home exercise programs in the form of play are recommended to maintain flexibility. For hand and wrist mobility, playing with blocks and play dough, finger painting, and coloring are recommended. For older children, playing Nintendo, cards, or musical instruments and putting together models or other crafts are recommended to maintain finger mobility. Active stretching of the gastrocnemius and soleus muscles may be achieved while participating in hill or incline walking, modified squatting activities, sit-to-stand activities from a low surface with heels as far down as possible, or standing on a wedge board while playing catch or other games. Overhead reaching games and throwing a medium- or large-sized ball overhead may assist with maintaining shoulder flexibility.

Gentle stretching and positioning are also recommended to prevent loss of joint flexibility such as long sitting with the back supported. Nighttime dynamic splints or positioning splints for ankle, knee, wrist, and fingers are recommended to increase or maintain range of motion. Although children often have heel cord contractures, daytime bracing is usually not recommended, especially if the child is receiving ERT. Active ankle movement throughout the day may assist in breaking down the GAGs. Because children have multiple joint involvement, we have found that a wear schedule that alternates between sides of the body is helpful in achieving increased splint-wearing adherence. For young children, splinting of multiple joints may be alternated during nap times so that children are not completely restricted while sleeping.

Therapists can help to establish a safe and effective endurance program for a child with MPS. Since children with MPS may have respiratory and cardiac complications, it is important to work closely with the child’s physicians to determine exercise parameters. Depending on the age of a child, disease severity, and cardiac complications, training intensity may start at 50% to 65% of maximal heart rate. For older children with MPS, maximum heart rate or training intensity can be determined by specific exercise stress tests using a treadmill or cycling protocol. In the clinic setting, for children with minimal or no cardiac disease, maximum heart rate is determined using the formula: maximum heart rate = 220 − the child’s age. Since children with MPS I and II often have joint pain and ligamentous laxity, high impact activities are not recommended. Low impact arm and leg movement to music, bicycling, walking, karate, swimming or pool aerobics, and hippotherapy are often recommended. As tolerated, children may gradually build up to 30 to 60 minutes in target heart rate for three to five days per week.

Children with MPS may have visual problems so therapeutic activities should be modified to accommodate these deficits by providing more verbal instructions, tactile/manual cues, or a combination of these assists. For some children, contrast tape on the edge of stairs and teaching compensatory strategies to use on curbs or uneven surfaces outdoors may help improve their independence and safety. Children with MPS may also have hearing impairments and may rely on demonstration and visual cues as well as tactile cues. Hearing aids are helpful for most children with MPS.8

Prescription, Application, and Fabrication of Devices and Equipment.

Although children with MPS are often ambulatory, they may need some assistive device for independent community mobility. Often young children with MPS can use commercially available strollers for longer periods of time because of their small stature. Other children, however, may need specialized strollers to accommodate portable oxygen or other respiratory equipment. Older children with MPS I-HS may need lightweight wheelchairs or powered wheelchairs for getting around school and the community. Children with MPS I-H who did not receive HSCT before 18 months of age or with a severe form of MPS II usually do not develop the ability to ambulate and need wheelchairs for mobility. In addition to typical factors considered when choosing a wheelchair and seating system, therapists should also consider the progressive nature of the disorder and the potential need for airway assistance for children with MPS. Children and youths with MPS I-S may have genu valgum, pes cavus, and stiff painful feet. Semirigid or soft accommodative foot orthotics may improve foot position and decrease foot pain.

Children with MPS who have a short stature may need adaptations in school for their desks and chairs or other work systems so that they can access their environment optimally. A small box or step under the feet help some children sit at the same height as their peers but keep their feet in contact with a surface. A small step or steps to access a sink or other school work stations may be appropriate.

Pompe Disease.

Regardless of the age or status of the client with Pompe disease, a comprehensive intervention plan will include goals addressing range of motion, strengthening, functional movement, endurance, respiratory function, and equipment needs.

Functional Training.

For infants and young children on ERT, the focus may be on typical developmental activities such as assuming and maintaining sitting, kneeling, and quadruped positions; crawling or creeping; and walking and getting up from the floor. For children who are not receiving ERT, functional training may focus on rolling, maintaining supported sitting, and propelling a wheelchair.

Therapeutic Exercise.

Specific muscle groups often requiring stretching include the hip flexors, hamstrings, gastrocsoleus, and the iliotibial band. Muscle shortness is typically due to muscle weakness and limited active movement; therefore, a positioning and stretching program is extremely important. Night or daytime splinting of ankles and knees for a mild restriction or for a child at risk may be helpful in preventing contractures. For the child with a contracture that does not respond to conservative techniques, an orthopedic referral is recommended. For the child who is able to use the muscle groups that have restricted length, it is important to provide a program that emphasizes regular active stretching of those muscle groups.

Strengthening activities are especially important for children with Pompe disease receiving ERT because they may have the opportunity to improve contractile properties of the muscles that were previously nonfunctional due to glycogen accumulation. Focus is on individual muscle groups as well as on patterns specific to functional tasks. Traditional strength training (as described under MPS) is appropriate for the older child. For the infant and young child, strengthening should focus on developmental positions and movements that can isolate the weakened muscle groups and provide a means for the family to carry over the training in daily activities. Examples of such activities include the following: (1) to increase neck stability, the parent may assume a reclined sitting position with the infant on the parent’s chest and encourage head lifting and then assume a progressively more reclined position until the child can lift his or her head while prone with or without a roll under his or her chest; (2) assisted transitions from supine to sitting by moving to side lying or prone and progressing to a situp with arm assistance; and (3) carrying techniques requiring activation of the head and trunk muscles. Young children may be encouraged to activate hip adductors, quadriceps, or plantar flexors by pushing through their feet or to activate abdominals when straightening their back against a wall in sitting position or pushing the lower back into the bed/floor while in the supine position. Using foam, squish toys, and play dough may be helpful with these activities. Home strengthening activities for the young child include use of tricycles (adapted with pedal straps and back support as needed), incorporating games that include climbing stairs or hills or doing obstacle courses that involve walking on balance beams, jumping, or climbing over or under obstacles.

Airway Clearance Techniques.

When addressing the cardiorespiratory system, the therapist focuses on strengthening muscles of respiration (including the diaphragm); maintaining mobility of the rib cage, shoulder, and pelvic girdle; and endurance training. For infants, prone activities not only assist with strengthening the trunk and shoulder girdle but also assist with mobilizing the rib cage. A physical therapist may teach a child and family diaphragmatic breathing exercises, airway clearance techniques, and body positioning for pulmonary drainage.

Adaptive Equipment.

Providing appropriate equipment may enable a child to attain functional mobility goals unattainable by direct intervention alone. Equipment can be used to advance function in addition to minimizing secondary conditions stemming from immobility and difficult positioning. Lower extremity orthotics will assist with preventing contractures and/or provide stability for a standing or an ambulatory program while protecting soft tissue or joints. Adapted tricycles may assist in improving strength, endurance, and function. Wheelchairs are critical for the child without a good prognosis for independent ambulation to achieve maximal community mobility. A wheelchair is also appropriate for the young child with potential to be an independent ambulator but who lacks independent mobility at the age critical for cognitive and social skill acquisition. Proper wheelchair positioning is important for skeletal alignment, efficiency of push, ability to maneuver, and ability to interact with peers. An older child with significant respiratory impairment may require a power chair for community mobility and a manual chair for home mobility. The therapist should consider current or future respiratory needs to ensure that the chair can accommodate an oxygen tank or ventilator tray attachment as needed. Tilt and recline are often necessary to prevent skin breakdown for the older child who has minimal movement abilities. Distal hand, deltoid, and head controls may be necessary for the young child has who has the ability to learn how to use these control systems.

SUMMARY AND RECOMMENDATIONS

LSDs are complex disorders affecting multiple organ systems with substantial variations in disease progression and severity. With newer medical interventions such as HSCT and ERT becoming available, therapists should be aware of these medical and surgical interventions in order to provide families with information about treatment options. Changes in medical interventions will affect the PT plan of care. For some of the LSDs for which new treatments are available, PT goals may switch from maintaining function or improving ease of caregiving to increasing function and decreasing caregiver assistance. Therapists should be aware of medical complications and precautions associated with each LSD and determine whether these problems will affect exercise and functional training for children with LSDs. Therapists should adapt activities to ensure safe functional improvements and teach exercise modifications to families, teachers, and others working with children on a daily basis. It is also important for therapists to be aware of current resources to provide families with the information for treatment options, support, and advocacy.

ACKNOWLEDGMENTS

We thank Stacey C. Dusing, MS, PT, Angela E. Rosenberg, DrPH, PT, and Dawn Phillips, MS, PT, for helpful suggestions and advice.

REFERENCES

1.Meikle P, Hopwood J, Clague A, et al. Prevalence of lysosomal storage disorders. JAMA. 1999;281:249–254.
2.Wilcox W. Lysosomal storage disorders: the need for better pediatric recognition and comprehensive care. J Pediatr. 2004;144:S3–S14.
3.Scriver C, Beaudet A, Sly W, et al, eds. The Metabolic and Molecular Bases of Inherited Disease, Vol. 3, 8th ed. New York: McGraw-Hill; 2001.
4.Wenger DA, Coppola S, Liu S-L. Insights into the diagnosis and treatment of lysosomal storage diseases. Arch Neurol. 2003;60:322–328.
5.Wraith JE. Advances in the treatment of lysosomal storage disease. Dev Med Child Neurol. 2001;43:639–646.
6.Beutler E, Grabowski GA. Gaucher disease. In: Scriver C, Beaudet A, Sly W, et al., eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 3, 8th ed. New York: McGraw-Hill; 2001:3635–3668.
7.Pastores G, Wallenstein S, Desnick R, et al. Bone density in type 1 Gaucher disease. J Bone Miner Res. 1996;11:1801–1807.
8.Neufeld EF, Muenzer J. The mucopolysaccaridoses. In: Scriver C, Beaudet A, Sly W, et al., eds. The Metabolic and Molecular Bases of Inherited Diseases, Vol 3, 8th ed. New York: McGraw; 2001:3421–3452.
9.Field R, Buchannan J, Copplemans M, et al. Bone-marrow transplantation in Hurler’s syndrome: effect on skeletal development. J Bone Joint Surg Br. 1994;76:975–978.
10.Hirschhorn R, Reuser A. Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. In: Scriver C, Beaudet A, Sly W, et al, eds. The Metabolic and Molecular Bases of Inherited Disease, Vol. 3, 8th ed. New York: McGraw-Hill; 2001:3389–3420.
11.Kishnani P, Howell R. Pompe disease in infants and children. J Pediatr. 2004;144:S35–S43.
12.Sly WS. Enzyme replacement therapy: from concept to clinical practice. Acta Paediatr Suppl. 2002;439:71–78.
13.Desnick RJ, Schuchman EH. Enzyme replacement and enhancement therapies: lessons from lysosomal disorders. Nat Rev Genet. 2002;3:954–966.
14.NIH Technology Assessment Panel on Gaucher Disease. Gaucher disease: current issues in diagnosis and treatment. JAMA. 1996;275:548–553.
15.Vellodi A, Young EP, Cooper A, et al. Bone marrow transplantation for mucopolysaccharidosis type I: experience of two British centers. Arch Dis Child. 1997;76:92–99.
16.Souillet G, Guffon N, Maire I, et al. Outcome of 27 patients with Hurler’s syndrome transplanted from either related or unrelated haematopoietic stem cell sources. Bone Marrow Transplant. 2003;31:1105–1117.
17.Krivit W. Stem cell bone marrow transplantation in patients with metabolic storage diseases. Adv Pediatr. 2002;49:359–378.
18.Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzyme deficiency—macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med. 1991;324:1464–1470.
19.Grabowski GA, Barton NW, Pastores G, et al. Enzyme therapy in type I Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med. 1995;122:33–39.
20.Masek BJ, Sims KB, Bove CM, et al. Quality of life assessment in adults with type I Gaucher disease. Qual Life Res. 1999;8:263–268.
21.Sly WS, Vogler C. Brain-directed gene therapy for lysosomal storage disease: going well beyond the blood-brain barrier. Proc Natl Acad Sci U S A. 2002;99:5760–5762.
22.Kakkis ED, Muenzer J, Tiller GE, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med. 2001;344:182–188.
23.Amalfitano A, Bengur AR, Morse RP, et al. Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. Genet Med. 2001;3:132–138.
24.van den Hout H, Reuser AJJ, Vulto AG, et al. Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet. 2000;356:397–398.
25.van den Hout JM, Reuser AJ, de Klerk JB, et al. Enzyme therapy for Pompe disease with recombinant human alpha-glucosidase from rabbit milk. J Inherit Metab Dis. 2001;24:266–274.
26.van der Ploeg AT, Winkel LPF, van Diggelen OP, et al. Preliminary findings in patients with late onset Pompe’s disease treated with recombinant human alpha-glucosidase from rabbit milk. J Inherit Metab Dis. 2002;25(Suppl 1):118.
27.Winkel LPF, Kamphoven JHJ, van den Hout HJMP et al. Morphological changes in muscle tissue of patients with infantile Pompe’s disease receiving enzyme replacement therapy. Muscle Nerve. 2003;25:743–751.
28.Dumas HM, Fragala MA, Haley SM, et al. Physical performance testing in mucopolysaccharidosis I: a pilot study. Pediatr Rehabil. 2004;7:125–131.
29.Haley SM, Coster WJ, Ludlow LH, et al. Pediatric Evaluation of Disability Inventory (PEDI): Development, Standardization and Administration Manual. Boston: Trustees of Boston University; 1992.
30.Haley SM, Fragala MA, Skrinar AM. Pompe disease and physical disability. Dev Med Child Neurol. 2003;45:618–623.
31.Haley S, Fragala MA, Aseltine R, et al. Development of a disease-specific instrument for Pompe disease. Pediatr Rehabil. 2003;6:77–84.
32.Haley SM, Fragala-Pinkham MA, Ni P, et al. Pediatric physical functioning reference curves. Pediatr Neurol. 2004;31:333–341.
33.Haley SM, Ni PS, Fragala-Pinkham MA, et al. An adaptive testing approach for assessing physical functioning in children and adolescents. Dev Med Child Neurol. 2005;47:113–120.
34.American Physical Therapy Association. Guide to physical therapist practice, second edition. Phys Ther. 2001;81:S19–S28.
35.Dusing S, Rosenberg A, Piner S. A retrospective study of discrepancy in gross and fine motor skills in children diagnosed with Hurler syndrome. Pediatr Phys Ther. 2004;16:52.
36.McEwen I. Providing Physical Therapy Services Under Parts B & C of the Individuals with Disabilities Education Act (IDEA). Section on Pediatrics. Alexandria, VA: American Physical Therapy Association; 2000.
37.American Academy of Pediatrics Committee on Sports Medicine and Fitness. Strength training by children and adolescents. Pediatrics. 2001;107:1470–1472.
38.Guy J, Micheli L. Strength training for children and adolescents. J Am Acad Orthop Surg. 2001;9:29–36.
39.Faigenbaum A, Milliken L, Loud R, et al. Comparison of 1 and 2 days per week of strength training. Res Q Exerc Sport. 2002;73:416–424.
40.Kilmer D. Response to restrictive strengthening exercise training in humans with neuromuscular disease. Am J Phys Med Rehabil. 2002;81:S121–S126.
41.Klepper S. Effects of an eight-week physical conditioning program on disease signs and symptoms in children with chronic arthritis. Arthritis Care Res. 1999;12:52–60.
42.Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr. 2004;144:S27–S34.
43.Haddad F, Jones D, Vellodi A, et al. Carpal tunnel syndrome in the mucopolysaccharidoses and mucolipidoses. J Bone Joint Surg Br. 1997;79:576–582.
44.Barton NW, Furbish FS, Murray GJ, et al. Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. Proc Natl Acad Sci U S A. 1990;87:1913–1916.
45.Weinreb NJ, Charrow J, Andersson HC, et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Am J Med. 2002;113:112–119.
46.Muenzer J, Lamsa JC, Garcia A, et al. Enzyme replacement therapy in mucopolysaccharidosis type II (Hunter syndrome): a preliminary report. Acta Paediatr Suppl. 2002;439:98–99.

    APPENDIX A

    Summary of Clinical Trials of Medical Therapeutics in LSDs
    Summary of Clinical Trials of Medical Therapeutics in LSDs:
    Summary of Clinical Trials of Medical Therapeutics in LSDs

    APPENDIX B

    MPS I-PPM-10 Item Version
    MPS I-PPM-10 Item Version:
    MPS I-PPM-10 Item Version

    APPENDIX C

    Internet Resources
    Internet Resources:
    Internet Resources
    Keywords:

    review article; review; tutorial; child development; lysosomal storage diseases; physical therapy/methods; lysosomal storage diseases/enzymology; lysosomal storage diseases/genetics; lysosomal storage diseases/therapy; bone marrow transplantation

    © 2005 Lippincott Williams & Wilkins, Inc.