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Positive Newborn Screen for Pompe Disease Leads to Anxiety in Families

Pruniski - Speaker World Symposium 2017Brianna Pruniski, MBBS

February 18, 2017—San Diego, California—A positive newborn screen for Pompe disease has been found to lead to anxiety in affected families.

This conclusion, based on results of a preliminary analysis of a qualitative interview study, was presented at the 13th Annual WORLDSymposium, from February 13–18.

Brianna Pruniski, MBBS, of Emory University, Atlanta, Georgia, explained that with lysosomal diseases being added to newborn screening panels in an increasing number of states, the controversial issue of identification of late-onset forms of lysosomal diseases via newborn screening has arisen.

Infantile-onset Pompe disease is usually diagnosed at 4–8 months. Muscles appear normal but are limp and weak, preventing infants from lifting their head or rolling over. As the disease progresses, heart muscles thicken and progressively fail. Without treatment, death usually occurs due to heart failure and respiratory weakness.

Infantile-onset Pompe disease usually comes to medical attention within the first few months of life. The usual presenting features are cardiomegaly (92%), hypotonia (88%), cardiomyopathy (88%), respiratory distress (78%), muscle weakness (63%), feeding difficulties (57%), and failure to thrive (50%).

The main clinical findings include floppy baby appearance, delayed motor milestones, and feeding difficulties. Moderate hepatomegaly may be present. Facial features include macroglossia, wide-open mouth, wide-open eyes, nasal flaring (due to respiratory distress), and poor facial muscle tone.

Cardiopulmonary involvement is manifested by increased respiratory rate, use of accessory muscles for respiration, recurrent chest infections, decreased air entry in the left lower zone (due to cardiomegaly), arrhythmias, and evidence of heart failure.

Median age at death in untreated cases is 8.7 months and is usually due to cardiorespiratory failure.

The usual initial investigations include chest X-ray, electrocardiogram, and echocardiography. Typical findings are those of an enlarged heart with nonspecific conduction defects. Biochemical investigations include serum creatine kinase (typically increased 10-fold) with lesser elevations of serum aldolase, aspartate transaminase, alanine transaminase, and lactic dehydrogenase.

Diagnosis is made by estimating acid alpha glucosidase activity in either skin biopsy (fibroblasts), muscle biopsy (muscle cells) or in white blood cells. The choice of sample depends on the facilities available at the diagnostic laboratory.

Late- or later-onset Pompe disease occurs later than 1 to 2 years and progresses more slowly than the infantile-onset form.

One of the first symptoms is a progressive decrease in muscle strength, starting with the legs and moving to smaller muscles in the trunk and arms, such as the diaphragm and other muscles required for breathing.

Respiratory failure is the most common cause of death. Enlargement of the heart muscles and rhythm disturbances are not significant features but do occur in some cases.

Later-onset Pompe disease differs from the infantile form principally in the relative lack of cardiac involvement. Onset is more insidious and progresses more slowly.

Cardiac involvement may occur but is milder than in the infantile form. Skeletal involvement is more prominent, with a predilection for the lower limbs.

Late-onset features include impaired cough, recurrent chest infections, hypotonia, progressive muscle weakness, delayed motor milestones, difficulty swallowing or chewing, and reduced vital capacity.

Prognosis depends on the age of onset of symptoms. Later-onset disease carries a better prognosis than the infantile-onset form.

In late-onset Pompe disease, creatinine kinases may be normal in some cases. Diagnosis is by estimation of enzyme activity in a suitable sample.

Respiratory complications are treated symptomatically. Physical and occupational therapy may be beneficial for some patients. Alterations in diet may provide temporary improvement but will not alter the course of the disease. Genetic counselling can provide families with information regarding risk in future pregnancies.

For early-onset forms, the ability to initiate early treatment can be lifesaving. Newborn screening, however, cannot always distinguish early- from late-onset cases. As a result, for conditions like late-onset Pompe disease, in which the first symptoms may not present for decades, infants diagnosed by newborn screening and their families may now spend years aware of their illness before symptoms appear. This phase presymptomatic awareness is little understood by the medical community.

To expand this understanding, Ms. Pruniski and colleagues have examined the effect of receiving a positive newborn for Pompe disease on parents and families. To date, in-depth qualitative interviews have been conducted with mothers of five children (two early-onset siblings and three late-onset patients) diagnosed with Pompe disease through newborn screening.

Interviews have explored these families’ experiences, their understanding of their child's disease, how they cope with the information, and what impact the diagnosis exerts on family life. Interviews have been transcribed and coded using MaxQDA v.12 and analysed for thematic trends using grounded theory. While data collection remains ongoing, preliminary analysis has uncovered several themes thus far.

All participants have discussed increased anxiety regarding their children’s health, exhibiting “hyperawareness” and vigilance for symptoms of Pompe disease. Uncertainty regarding their child’s future, when to start treatment, and the having more children has also been reported.

Families who have experienced greater support from friends and family have been better able to cope with the anxiety. Finally, while the experience has been difficult at times for all interviewed, parents expressed appreciation for the information and felt as though, ultimately, the knowledge is both useful and empowering moving forward.

Ms. Pruniski concluded that a positive newborn screen for Pompe disease has been found to lead to significant anxiety in affected families.

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Molecular Genetics and Metabolism is a contribution to the understanding of the metabolic basis of disease. The journal publishes articles describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, occasional minireviews reporting timely advances as well as brief communications and letters to the editor are considered.

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