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Activity of daily living for Morquio syndrome type A
Abstracts / Molecular Genetics and Metabolism 117 (2016) S14–S124
lyso-Gb3 in clinical samples. In this study, we measured lyso-Gb3 in plasma samples from various types of Fabry patients, functional variants (E66Q), and healthy subjects. The mean plasma concentrations of lyso-Gb3 were 150 ± 53 nM for the classic Fabry males (n = 11), 13.2 ± 12.6 nM for the later-onset Fabry males (n = 11), 8.3 ± 8.1 nM for the Fabry females (n = 6), 0.33 ± 0.16 nM for the functional variants (n = 13), and 0.39 ± 0.10 nM for the healthy subjects (n = 14). Most of the Fabry females could be distinguished from healthy subjects, and there was no difference between the functional variant group and the healthy subject one. The results facilitated to elucidate the basis of Fabry disease by combining the results of clinical, pathological and structural analysis. These results showed that the measurement of glycosphingolipids by means of LCMS/MS is useful for basic and clinical investigation of Fabry disease. doi:10.1016/j.ymgme.2015.12.460
303 Morquio syndrome type A airway and anesthetic considerations Shunji Tomatsu, Christopher J. Goff, William G. Mackenzie, Robert Brislin, James S. Reilly, Mary Theroux, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States Patients with Morquio syndrome type A have short stature, kyphoscoliosis, and restrictive lung due to thoracic bone deformity. Patients with Morquio syndrome type A have a higher incidence of airway abnormalities which results in an increased risk of complications from anesthesia, even when undergoing short procedures. However, to date there was no systemic description on the anesthesia issue in Morquio syndrome type A. We retrospectively reviewed our experience of anesthesia from 1993 to 2014 and identified 37 patients with Morquio syndrome type A who have undergone general anesthesia procedures. We collected data including demographics, the otolaryngology procedures, difficulty of the airways, intubation techniques used, extubation success, need for tracheotomy, and postoperative admissions including ICU care. Thirty-seven patients underwent 195 surgical procedures. Complete data analyses were available for 149 procedures. Twenty-two of the 37 patients (59%) were identified as having a difficult airway. Nine of 22 patients (41%) with difficult airways were consistently difficult to intubate requiring multiple attempts for intubation for every anesthetic they received. Seven of 9 patients (78%), who were difficult to intubate previously, had their cervical spinal fusion. Physical characteristics indicative of difficulty with mask ventilation and intubation included restricted mouth opening and a short neck with a limited range of motion. Twenty-eight of 37 patients (76%) had pectus excavatum or carinatum. In conclusion, preoperative planning and cooperation among the anesthesiology, pulmonology, and otolaryngology should provide safe airway management during surgical procedures. Airway management techniques such as video laryngoscopes help the physcian achieve this goal. Necessity for multiple surgical procedures in most patients with Morquio syndrome type A makes it a compassionate and safer approach to combine airway examination with another surgical procedure. doi:10.1016/j.ymgme.2015.12.461
304 Activity of daily living for Morquio syndrome type A Shunji Tomatsua, Suzuki Yasuyukib, Eriko Yasudaa, Tadao Oriib, Kazuki Sawamotoa, aNemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States, bGifu University, Gifu, Japan
S113
The simple questionnaire of activity of daily living (ADL) has not been available to patients with mucopolysaccharidosis IVA (MPS IVA; Morquio syndrome type A). The aim of this study was to evaluate ADL in patients with MPS IVA, using a simple designed ADL questionnaire. Clinical phenotypes and therapeutic efficacies were assessed between the age-matched controls and untreated and treated patients. The ADL questionnaire comprises three domains: “movement,” “movement with cognition,” and “cognition.” Each domain has four subcategories rated on a 5-point scale based on the level of assistance. We also scored signs and symptoms unique to MPS by 12 subcategories (five points per category), providing 60 points in total. The questionnaire was collected from 145 healthy Japanese controls (0.33-43.55 years) and 80 patients with MPS IVA (0.71-70.46 years). The patient cohort consisted of 64 severe and 16 attenuated phenotypes; four patients treated with HSCT, 30 patients treated with ERT (over one year), and 46 untreated patients. Three patients treated by HSCT were defined as a severe phenotype. Patients with severe phenotypes provided a lower ADL score than control subjects and attenuated phenotypes in domains of “movement” and “movement with cognitive function.” Patients with HSCT gave a higher ADL score than untreated patients, and the patient with HSCT at 4 years provided the highest score in all patients. Scores in ERT patients increased up to 10 years, and thereafter, were spread out lower than those in the age-matched control subjects. There was a trend of decline in ADL scores of patients treated or untreated with ERT. In conclusion, we have assessed the feasibility of the ADL questionnaire in patients with MPS IVA, providing a simple method for clinical phenotypes and therapeutic efficacy. doi:10.1016/j.ymgme.2015.12.462
305 Obstructive airway in mucopolysaccharidosis IVA Shunji Tomatsua, Lauren W. Averilla, Christian Pizarroa, Mary Therouxa, Kazuki Sawamotoa, Tadao Oriib, aNemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States, bGifu University, Gifu, Japan Patients with severe tracheal obstruction in Morquio syndrome type A are at risk of dying of sleep apnea and related complications. Tracheal obstruction leads to life-threatening complications during anesthesia as a result of the difficulty in managing the upper airway. Detailed description of the obstructive pathology of the trachea is not available due to lack of a homogenous group of Morquio syndrome type A patients. We present the cases with significant tracheal obstruction who were unrecognized due to the difficulty in interpreting tracheal narrowing airway symptoms. Our goal is to provide the guidelines in the management of these patients that allow earlier recognition and intervention of tracheal obstruction. Sagittal magnetic resonance imaging (MRI) images of the cervical spine of 28 Morquio syndrome type A patients (12 ± 8.14 years) showed that 19/28 (67.9%) patients had at least 25% tracheal narrowing and that narrowing worsened with age (all 8 patients over 15 years had greater than 50% narrowing). Eight of 28 patients were categorized as severe (N75%) tracheal narrowing when images were evaluated in neutral head and neck position. Of the 19 patients with tracheal narrowing, compression by the tortuous brachiocephalic artery was the most common cause (n = 15). Evidence of such tracheal narrowing was evident as early as at 2 years of age.The etiology of tracheal impingement by the brachiocephalic artery appears to be due to a combination of the narrow thoracic inlet crowding structures and the disproportionate growth of trachea and brachiocephalic artery to the chest cavity. In conclusion, tracheal narrowing, often due to impression from the crossing tortuous
lyso-Gb3 in clinical samples. In this study, we measured lyso-Gb3 in plasma samples from various types of Fabry patients, functional variants (E66Q), and healthy subjects. The mean plasma concentrations of lyso-Gb3 were 150 ± 53 nM for the classic Fabry males (n = 11), 13.2 ± 12.6 nM for the later-onset Fabry males (n = 11), 8.3 ± 8.1 nM for the Fabry females (n = 6), 0.33 ± 0.16 nM for the functional variants (n = 13), and 0.39 ± 0.10 nM for the healthy subjects (n = 14). Most of the Fabry females could be distinguished from healthy subjects, and there was no difference between the functional variant group and the healthy subject one. The results facilitated to elucidate the basis of Fabry disease by combining the results of clinical, pathological and structural analysis. These results showed that the measurement of glycosphingolipids by means of LCMS/MS is useful for basic and clinical investigation of Fabry disease. doi:10.1016/j.ymgme.2015.12.460
303 Morquio syndrome type A airway and anesthetic considerations Shunji Tomatsu, Christopher J. Goff, William G. Mackenzie, Robert Brislin, James S. Reilly, Mary Theroux, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States Patients with Morquio syndrome type A have short stature, kyphoscoliosis, and restrictive lung due to thoracic bone deformity. Patients with Morquio syndrome type A have a higher incidence of airway abnormalities which results in an increased risk of complications from anesthesia, even when undergoing short procedures. However, to date there was no systemic description on the anesthesia issue in Morquio syndrome type A. We retrospectively reviewed our experience of anesthesia from 1993 to 2014 and identified 37 patients with Morquio syndrome type A who have undergone general anesthesia procedures. We collected data including demographics, the otolaryngology procedures, difficulty of the airways, intubation techniques used, extubation success, need for tracheotomy, and postoperative admissions including ICU care. Thirty-seven patients underwent 195 surgical procedures. Complete data analyses were available for 149 procedures. Twenty-two of the 37 patients (59%) were identified as having a difficult airway. Nine of 22 patients (41%) with difficult airways were consistently difficult to intubate requiring multiple attempts for intubation for every anesthetic they received. Seven of 9 patients (78%), who were difficult to intubate previously, had their cervical spinal fusion. Physical characteristics indicative of difficulty with mask ventilation and intubation included restricted mouth opening and a short neck with a limited range of motion. Twenty-eight of 37 patients (76%) had pectus excavatum or carinatum. In conclusion, preoperative planning and cooperation among the anesthesiology, pulmonology, and otolaryngology should provide safe airway management during surgical procedures. Airway management techniques such as video laryngoscopes help the physcian achieve this goal. Necessity for multiple surgical procedures in most patients with Morquio syndrome type A makes it a compassionate and safer approach to combine airway examination with another surgical procedure. doi:10.1016/j.ymgme.2015.12.461
304 Activity of daily living for Morquio syndrome type A Shunji Tomatsua, Suzuki Yasuyukib, Eriko Yasudaa, Tadao Oriib, Kazuki Sawamotoa, aNemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States, bGifu University, Gifu, Japan
S113
The simple questionnaire of activity of daily living (ADL) has not been available to patients with mucopolysaccharidosis IVA (MPS IVA; Morquio syndrome type A). The aim of this study was to evaluate ADL in patients with MPS IVA, using a simple designed ADL questionnaire. Clinical phenotypes and therapeutic efficacies were assessed between the age-matched controls and untreated and treated patients. The ADL questionnaire comprises three domains: “movement,” “movement with cognition,” and “cognition.” Each domain has four subcategories rated on a 5-point scale based on the level of assistance. We also scored signs and symptoms unique to MPS by 12 subcategories (five points per category), providing 60 points in total. The questionnaire was collected from 145 healthy Japanese controls (0.33-43.55 years) and 80 patients with MPS IVA (0.71-70.46 years). The patient cohort consisted of 64 severe and 16 attenuated phenotypes; four patients treated with HSCT, 30 patients treated with ERT (over one year), and 46 untreated patients. Three patients treated by HSCT were defined as a severe phenotype. Patients with severe phenotypes provided a lower ADL score than control subjects and attenuated phenotypes in domains of “movement” and “movement with cognitive function.” Patients with HSCT gave a higher ADL score than untreated patients, and the patient with HSCT at 4 years provided the highest score in all patients. Scores in ERT patients increased up to 10 years, and thereafter, were spread out lower than those in the age-matched control subjects. There was a trend of decline in ADL scores of patients treated or untreated with ERT. In conclusion, we have assessed the feasibility of the ADL questionnaire in patients with MPS IVA, providing a simple method for clinical phenotypes and therapeutic efficacy. doi:10.1016/j.ymgme.2015.12.462
305 Obstructive airway in mucopolysaccharidosis IVA Shunji Tomatsua, Lauren W. Averilla, Christian Pizarroa, Mary Therouxa, Kazuki Sawamotoa, Tadao Oriib, aNemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States, bGifu University, Gifu, Japan Patients with severe tracheal obstruction in Morquio syndrome type A are at risk of dying of sleep apnea and related complications. Tracheal obstruction leads to life-threatening complications during anesthesia as a result of the difficulty in managing the upper airway. Detailed description of the obstructive pathology of the trachea is not available due to lack of a homogenous group of Morquio syndrome type A patients. We present the cases with significant tracheal obstruction who were unrecognized due to the difficulty in interpreting tracheal narrowing airway symptoms. Our goal is to provide the guidelines in the management of these patients that allow earlier recognition and intervention of tracheal obstruction. Sagittal magnetic resonance imaging (MRI) images of the cervical spine of 28 Morquio syndrome type A patients (12 ± 8.14 years) showed that 19/28 (67.9%) patients had at least 25% tracheal narrowing and that narrowing worsened with age (all 8 patients over 15 years had greater than 50% narrowing). Eight of 28 patients were categorized as severe (N75%) tracheal narrowing when images were evaluated in neutral head and neck position. Of the 19 patients with tracheal narrowing, compression by the tortuous brachiocephalic artery was the most common cause (n = 15). Evidence of such tracheal narrowing was evident as early as at 2 years of age.The etiology of tracheal impingement by the brachiocephalic artery appears to be due to a combination of the narrow thoracic inlet crowding structures and the disproportionate growth of trachea and brachiocephalic artery to the chest cavity. In conclusion, tracheal narrowing, often due to impression from the crossing tortuous