Childhood Pompe disease: clinical spectrum and genotype in 31 patients.

BACKGROUND: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the Netherlands, between 1975 and 2012, excluding those with the classic-infantile form. None were treated with enzyme replacement therapy at the time of evaluation. We collected information on first symptoms, diagnosis, use of a wheelchair and/or respirator, and enzyme and mutation analysis and assessed muscle strength, pulmonary function, and cardiac parameters. RESULTS: Thirty-one patients participated. Median age at symptom onset was 2.6 years (range 0.5-13y) and at diagnosis 4.0 years. Most first problems were delayed motor development and problems related to limb-girdle weakness. Fatigue, persistent diarrhea and problems in raising the head in supine position were other first complaints. Ten patients were asymptomatic at time of diagnosis. Five of them developed symptoms before inclusion in this study. Over 50 % of all patients had low or absent reflexes, a myopathic face, and scoliosis; 29 % were underweight. Muscle strength of the neck flexors, hip extensors, hip flexors, and shoulder abductors were most frequently reduced. Pulmonary function was decreased in over 48 % of the patients; 2 patients had cardiac hypertrophy. Patients with mutations other than the c.-32-13T > G were overall more severely affected, while 18 out of the 21 patients (86 %) with the c.-32-13T > G/'null' genotype were male. CONCLUSIONS: Our study shows that Pompe disease can present with severe mobility and respiratory problems during childhood. Pompe disease should be considered in the differential diagnosis of children with less familiar signs such as disproportional weakness of the neck flexors, unexplained fatigue, persistent diarrhea and unexplained high CK/ASAT/ALAT. Disease presentation appears to be different from adult patients. The majority of affected children with GAA genotype c.-32-13T > G/'null' appeared to be male.

Ten years of the international Pompe survey: patient reported outcomes as a reliable tool for studying treated and untreated children and adults with non-classic Pompe disease.

Pompe disease is a rare, progressive lysosomal storage disorder for which enzyme therapy (ERT) became available in 2006. Four years earlier, the IPA/Erasmus MC survey, an international longitudinal prospective survey, was established to collect information on the natural course of the disease and its burden on patients. The survey is a collaboration between Erasmus MC University Medical Center and the International Pompe Association (IPA) and comprises an annual questionnaire that was specifically designed to assess the symptoms and problems of the disease. Here we review our results of over 10 years of follow-up, and discuss the survey's contribution to the field. Tracking 408 Pompe patients between 2002 and 2013, the cumulative data reveals the broad range of clinical manifestations that interfere with patients' lives. The survey allowed us to quantify the rate of disease progression and the positive effects of ERT on patients' quality of life, fatigue, and participation in daily life. Furthermore, it showed for the first time that survival is reduced in adult Pompe disease and improved by ERT. Our results show that a patient survey can serve as a valuable and reliable tool for obtaining quantifiable information on the natural course of a rare disease and on the effects of therapy in a large cohort over a very long time. Most importantly, by working with patient reported outcomes, the survey provides the data that is truly relevant to the patient and complementary to clinical datasets.

Determining presence of lung disease in young children with cystic fibrosis: lung clearance index, oxygen saturation and cough frequency.

BACKGROUND: Accurate assessment of pulmonary status in young children with cystic fibrosis (CF) requires sensitive and objective monitoring techniques. OBJECTIVES: This study aimed to evaluate the feasibility of lung clearance index (LCI) calculated from multiple breath washout (MBW), home nocturnal pulse oximetry and home nocturnal cough recording in young children with CF, and determine whether these tests can distinguish CF patients from healthy controls. METHODS: We performed a prospective cross-sectional study in 20 CF patients and 30 healthy children aged 0-4 years. MBW was performed in awake and unsedated children at the outpatient clinic using a commercially available device. Measurements of nocturnal oxygen saturation and nocturnal cough were done at home using a pulse oximeter and an audiometer. RESULTS: There was a significant difference in mean LCI between healthy children and CF patients (LCI 7.1 vs. 9.3, p<0.001). Nocturnal oxygen saturation was normal in both groups and did not significantly differ between the groups. Similarly, cough showed no differences between both groups. Cough varied widely between children and between nights. Success rates for saturation and cough measurements were 90% and were similar for CF patients and healthy children. Success rate for LCI was 75% for CF patients and 50% for healthy children. CONCLUSIONS: Measurements of LCI, nocturnal oxygen saturation and cough were feasible in young children; however LCI was the only variable that showed a significant difference between children with CF and healthy children.