Non-invasive Functional Assessment and Pathogenesis of Morquio A

DIAGNOSTIC_TEST

Imaging, gait analysis, growth, joint test, hearing test, questionnaire, etc.

This study includes 15 major assessments: clinical assessment procedures; anthropometric measurements; activity of daily living and quality-of-life questionnaires; gait kinematics and kinetics analysis; pulmonary function tests (PFT); skeletal radiographs and dual-energy x-ray absorptiometry (DXA); MRI in cervical spine, temporal bones, and hip; computed tomography angiography (CTA) for tracheal obstruction; CT for temporal bones; anesthetic encounters; joint mobility; hearing function; biochemical analyses; and pathological analyses.

Change of Total body length

Time frame: baseline, 18 months, 36 months, 48 months

cm: The patient lies on a flat surface with knees flattened to extend the legs fully. Standing height will also be measured

Change of Body mass index (BMI)

Time frame: baseline, 18 months, 36 months, 48 months

BMI: BMI is a measure of body fat based on height and weight. BMI is a person's weight in kilograms divided by the square of height in meters.

Change of Height velocity

Time frame: baseline, 18 months, 36 months, 48 months

cm/year: calculating height velocity is a simple matter of measuring a height at two points in time and then dividing the change by the amount of time (year).

Change of QOL questionnaire

Time frame: baseline, 18 months, 36 months, 48 months

Score: The questionnaire comprises three domains: "Movement," "Movement with cognition," and "Cognition." Each domain has 20 scores. Total score is 60. Higher scores means a better ADL.

Change of Joint Mobility

Time frame: baseline, 18 months, 36 months, 48 months

Angle Degree: Evaluate the degree of hyperlaxity in the metacarpophalangeal (MCP) joint of the index finger. Each test will be repeated three times to get the average forces from each patient. The device measures the angle and torque at the 2nd metacarpophalangeal joint as it is passively extended. It expresses as rad/Nm.

Change of Skeletal survey by x-rays

Time frame: baseline, 36 months

Distance (mm); PA hands bilaterally, Metacarpal 2nd,3rd, 4th, and 5th, bone age assessment. Assessment is performed with a radiograph of the non-dominant hand with a single DP view that includes the distal radius and ulna and all the fingers. Appearances of the carpal bones, metacarpal, phalanges, radius and ulna are compared to standardized versions in one of two main atlases: * Greulich \& Pyle atlas presents a single standardized image for a range of ages of each gender * Tanner-Whitehouse atlas involves the scoring of each carpal bone, the radius and ulna leading to a total score, from which age can be estimated mm; AP lower extremities from pelvis to floor on a single image mm; Length of tibia and fibula mm; For children \< 7 yrs; measure between the epiphyseal plates, measure lengths of femur and tibia.

Change of MRI in cervical spine (distance)

Time frame: baseline, 18 months, 36 months, 48 months

Distance (mm); The following measurements will be used to define cervical instability and stenosis; 1) powers ratio exceeding 1.0 for occipito-C1 instability; 2) less than 13 mm of space available for the cord (SAC) at C1-2 for canal stenosis; 3) ADI measuring more than 5 mm for C1-2 instability; 4) greater than 2 mm offset of C2 interiorly on C3 measured at the spino-laminar (Swishuk's) line for C2-3 instability; 5) sagittal translation in flexion and extension more than 3.5 mm for sub-axial instability.

Change of CT angiography (CTA) (area)

Time frame: baseline, 36 months

Area (mm3); Tracheal cross-sectional area will be measured (mm3) at the cervical, thoracic inlet and intrathoracic levels and compared against normative age-matched controls The cross-sectional shape of the trachea will be described using previously described nomenclature. Tortuosity and deviation of the trachea will be described. Course and tortuosity of the innominate artery and relationship to tracheal narrowing will be described. Anteroposterior diameter of the thoracic inlet will be measured. CTA measurements of trachea will be correlated with tracheal diameter measurements obtained from MRI of the cervical spine in order to determine if MR of the cervical spine provides an adequate level of detail to serve as the primary screening tool for tracheal obstruction, thereby reserving CTA for severe cases requiring detailed tracheal information before anesthesia and those requiring tracheal reconstruction.

Change of Anesthetic encounters

Time frame: baseline, 18 months, 36 months, 48 months

Score (1-5); Those patients who undergo during the study period, will have their airway management assessed for difficulty and scored on a 5 point scale . Difficult upper and lower airway scoring (1) normal (2) Difficult upper airway only but relieved easily (3) Difficult upper airway and difficult tracheal intubation (5) Failed upper airway management or tracheal intubation

Change of Pulmonary Function Tests (CO2 %)

Time frame: baseline, 18 months, 36 months, 48 months

Co2%: Air flow, volume data, flow-volume loops, and oximetry signals using PNT will be recorded using pediatric PFT systems (CO2SMO, Respironics, Wallingford, CT) and software packages (Analysis Plus, Novametrix Medical Systems, Wallingford, CT).

Change of Pulmonary Function Tests (Resistance)

Time frame: baseline, 18 months, 36 months, 48 months

Resistance (R); The method is rapid (20 sec) allowing the evaluation of total respiratory impedance (Zrs) that is based on total respiratory resistance (Rrs) and total respiratory reactance (Xrs). Rrs includes the airway, lung tissue, and chest wall resistance, whereas Xrs represent the balance of two (an elastic and an inertial) components.

Change of Pulmonary Function Tests (percent Rib Cage)

Time frame: baseline, 18 months, 36 months, 48 months

percent Rib Cage; TAM is a measure of chest wall motion and breathing patterns, as well as tidal volume contribution to the thoracic and abdominal compartments. TAM uses two elastic bands, one placed around the ribcage (RC) at the nipple line, and one placed around the abdomen (ABD) at the umbilicus. Two bands measure TAM (movement \& synchrony) of the patient's RC and ABD.

Change of Z-score of Bone mineral density (BMD)

Time frame: baseline, 18 months, 36 months, 48 months

Lumbar spine and bilaterally distal femurs BMD will be measured using Hologic 1000 W DEXA. The following variables will be collected from each scan: BMD, bone mineral content (BMC), and bone area. Z-scores will be calculated from published norms for the lateral distal femur and from the Hologic pediatric reference database for the spine. Z-scores will be calculated from published norms for the lateral distal femur and from the Hologic pediatric reference database for the spine.

Change of Hearing function (db SPL)

Time frame: baseline, 18 months, 36 months, 48 months

Otoacoustic noise levels (db SPL); Thresholds of middle ear muscle reflex will be obtained to assess the middle ear. The range of testing levels ranges 70 and 105 dB SPL, and the thresholds above 100 dB SPL or no response will be considered as abnormal responses.

Change of Gait analysis (Nm/kg)

Time frame: baseline, 18 months, 36 months, 48 months

Children's movement will be analyzed with a 3D motion analysis system while they walk a 30 m walkway. Joint kinetics will be analyzed using force plates that are embedded in the walkway. The investigators will evaluation joint kinematics (Nm/kg - Newton meters/kg).

Change of Biochemical biomarkers (KS)

Time frame: baseline, 18 months, 36 months, 48 months

Measure KS in blood (ng/ml). LC/MS/MS will be used to analyze the disaccharides produced from KS. KS will be digested to disaccharides by keratanase II. Blood KS is expressed as ng/ml.

Change of Biochemical biomarkers (C6S)

Time frame: baseline, 18 months, 36 months, 48 months

Measure C6S in blood (ng/ml). LC/MS/MS will be used to analyze the disaccharides produced from C6S. C6S will be digested to disaccharides by keratanase II. Blood C6S is expressed as ng/ml.

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