pompe 's disease ( pd ) or glycogen storage disease type ii ( gsdii ) is a rare autosomal recessive neuromuscular disorder which arises as the result of deficiency in lysosomal enzyme acid -glucosidase ( gaa ) ( 1 , 2 ) .
therefore , glycogen is accumulated in lysosomal vacuoles in various tissues such as smooth muscles , cardiac and skeletal .
the accumulation of glycogen disrupts the cell function and causes the cell to grow and the lysosomes to be ruptured ( 3 ) .
the outbreak of pompe disease is approximately 1 in every 40000 live births ( 4 ) .
this disease is categorized into two forms of infantile onset pompe disease ( iopd ) and late - onset pompe disease ( lopd ) based on the age of outbreak , the organ involved and the rate of the disease s progression ( 5 ) .
the classical type is a fast progressive disorder which is associated with hypotonia , paresis , cardiomegaly , hepatomegaly , and death in the first year of life following heart - respiratory failure . in the non - classical type ,
the symptoms appear at the first year of life but the disease proceeds much slower and cardiomyopathy is less severe ( 3 , 6 ) . complete or near - complete deficiency in lysosomal enzyme acid -glucosidase is peculiar to this type of the disease ( 7 ) .
iopd patients may also have other symptoms including macroglossia , failure to thrive , and absent deep tendon reflexes ( 8 , 9 ) . due to the low prevalence of the disease and the vast range of symptoms ,
thus , it is essential to know more about the natural history of pompe so that the treatment will be initiated at an appropriate time .
measuring gaa enzyme activity in cultured fibroblasts of skin and muscle biopsy are two specific standard and reliable diagnostic methods for the diagnosis of this disease ( 5 ) .
however , because of its easiness , the examination of enzyme activity in a blood sample ( leukocytes , lymphocytes , or dried blood spot ) gradually became one of the common and also reliable techniques for the diagnosis of pd ( 10 ) .
for a long time , iopd was incurable and supportive cares such as respiratory protection was the only way to control it .
but in 2006 , enzyme replacement therapy ( ert ) by recombinant human enzyme acid -glucosidase ( rhgaa ) was approved by fda ( 11 , 12 ) . of the health benefits of ert in infants with pompe
, we can refer to the increase of -glucosidase activity in skeletal muscle , the improvement of muscle performance and structure , the reduction in size of the heart , the enhancement of cardiac function , the prevention of respiratory failure , and the increase in years of life in the patients ( 13 ) .
the best results from ert treatment are achieved when the patient is diagnosed in time and before the outbreak of irrecoverable damages ( 9 ) .
in this study , the clinical symptoms of iopd patients and their outcome after months of ert were investigated and compared to the results of previous studies .
an enzyme assay was executed on dried blood spot from september 2012 onwards for all patients who according to clinical findings , exhibited typical symptoms of iopd .
the patients who had both typical symptoms of the disease and enzyme deficiency were put under investigation .
the cases under investigation were fully examined and specially observed in terms of muscular power , cognition , motor development , and cardiac performance . then , ecg and echocardiography was taken . after obtaining informed consent from the patients
, they started to receive ert 20 mg / kg/2wk , and were followed up for maximum duration of 117 weeks .
based on the clinical symptoms and the enzyme assay , six infants were recognized as iopd .
all these six ( 100% ) patients had left ventricular hypertrophy along with degrees of hypertrophic cardiomyopathy . four ( 67% ) patients had generalized hypotonia .
the age range for the onset of symptoms was 1 to 7 ( average 3.8 ) months and the age range for the diagnosis of the disease was 2 to 8 ( average 4.7 ) months .
three patients expired because of severe respiratory infection while they had received 3 or less doses of ert .
however , he was running a fever from morning ; and received the last dose of the medication in a hospital , personnel of which had no previous familiarity with this medication .
therefore , it seems that he was infected with acute cardiorespiratory failure due to an underlying acute respiratory illness . until the preparation of this article , the remaining two patients have been followed for 117 and 65 weeks respectively .
another significant issue is that the two patients who responded finely to the treatment , only had cardiac symptoms at the beginning ; while all four patients who in addition to cardiac involvement also suffered from hypotonia , expired . during ert ,
no other side effect of myozyme , such as fever , body pain and allergic reactions were seen in our patients .
ert with alglucosidase alfa which was approved by fda in 2006 has the capability to decrease mortality and morbidity in iopd .
various studies have been conducted on the effectiveness of ert . a multi - center study on 18 patients with iopd who received ert up to 36 months , showed different results .
their survival rate at age 24 months was 94.4% and at age 36 months it was 72% .
eleven of the 18 patients had significant improvement in motor skills , but other 7 patients were unable to achieve sustained motor gains after 3 years of age ( 14 ) .
another study has been performed on 21 iopd patients who were treated with alglucosidase alfa for about 120 weeks . at the end of the study ,
71% of the patients were alive , left ventricular mass improved or remained normal in all of them , and 62% achieved new motor milestones ( 14 ) .
a new article about different aspects of ert in iopd patients has concluded that factors that affect the outcome of iopd patients include : age at start of ert , genotype , muscle fiber type and multidisciplinary care ( 15 ) .
four out of six ( 67% ) pompe patients died during the first weeks of the treatment .
the reason behind their death was severe respiratory infection ; and the cause of another one s death was acute cardiorespiratory collapse during receiving alglucosidase alfa , underlying reason of which was not truly recognized . only two ( 33% ) patients remained alive , who after 65 and 117 weeks , are perfectly in the age - related normal state in terms of cardiorespiratory and motor performance .
why is the survival rate of iopd patients in our study poorer than in other studies ?
it seems that inattention to infection control skills and multidisciplinary care resulted in death in 3 patients .
we did not perform genetic study in some of the patients , therefore , poor survival of our patients can also be related to their genotype .
thus , it seems that to enhance iopd patients ' survival strict cardiorespiratory care and infection control techniques also must be applied during the first months of ert . moreover ,
special care should be observed not to get nosocomial infections during several hospitalizations in order to receive ert .
in addition , one of the most important causes of poor response to ert can be antibody production against the drug . therefore , according to other studies , it is recommended to determine crim negative patients that are highly prone to antibody production , and use immune tolerance induction to diminish the antibody titer and increase the effectiveness of ert ( 16 , 17 ) .
two of them who remained alive only had cardiac involvement symptoms at the beginning and did not suffer from generalized hypotonia .
however , the four patients who died had both heart muscle involvement and generalized hypotonia right from the beginning .
moreover , since early diagnosis and fast treatment can improve prognosis , it is suggested that a widespread study be conducted to examine the cost - effectiveness of infantile screening for pompe disease . in spite of ert in our patients with iopd ,
more attention to infection control skills and multidisciplinary care are needed to improve the outcome of the disease .
additionally , it seems that the patients with generalized hypotonia suffer from a much worse prognosis than the patients who do not show obvious generalized hypotonia .
the most important limitation of this study is the low sample size . according to the rarity of this disease
abbreviations : ef , ejection fraction ; ivsd , intraventricular septum in diastole ; ivss , intraventricular septum in systole ; lvidp , left ventricular internal diameter in diastole ; lvids , left ventricular internal diameter in systole ; lvpwd , left ventricular posterior wall in diastole ; lvpws , left ventricular posterior wall in systole .
abbreviations : ef , ejection fraction ; ivsd , intraventricular septum in diastole ; ivss , intraventricular septum in systole ; lvidp , left ventricular internal diameter in diastole ; lvids , left ventricular internal diameter in systole ; lvpwd , left ventricular posterior wall in diastole ; lvpws , left ventricular posterior wall in systole .
 background : infantile onset pompe disease ( iopd ) is a rare autosomal recessive neuromuscular disorder . 
 it is associated with cardiomegaly , hypotonia , paresis , and death in the first year of life . since 2006 , following the use of alglucosidase alfa as enzyme replacement therapy ( ert ) , the patients survival is improved to a noticeable extent.objectives:the purpose of this study is to examine the outcome of iopd patients in south of iran and the degree of responsiveness to ert.patients and methods : all patients who were diagnosed with iopd on the bases of clinical symptoms , and enzyme assay on dried blood spot , were included in the study ; and were followed up regarding cardiac function , locomotor activity , and cognition.results:six patients with iopd were identified . 
 all these six patients suffered from hypertrophic cardiomyopathy ( hcm ) . 
 four ( 67% ) of them also had generalized hypotonia . 
 three patients expired during the first weeks due to severe respiratory infection . 
 one of them also got involved with acute cardiopulmonary failure while receiving the fifth dose of ert ; and expired . 
 however , the remaining two patients had a significant improvement after the maximum of 117 weeks of following up both cardiac and locomotor findings . 
 these two patients were the same patients who showed cardiac symptoms from the beginning but did not have generalized hypotonia.conclusions:although ert has a significant effect on enhancing the survival of iopd patients , it should be associated with meticulous heart - respiratory cares during the first months of treatment and preventing infection especially nosocomial infections . 
1. Background
2. Objectives
3. Patients and Methods
4. Results
5. Discussion