Diagnosing mucopolysaccharidosis IVA

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc., met to develop recommendations for diagnosis. The following conclusions were reached. Due to the wide variation and subtleties of radiographic findings, imaging of multiple body regions is recommended. Urinary glycosaminoglycan analysis is particularly problematic for MPS IVA and it is strongly recommended to proceed to enzyme activity testing even if urine appears normal when there is clinical suspicion of MPS IVA. Enzyme activity testing of GALNS is essential in diagnosing MPS IVA. Additional analyses to confirm sample integrity and rule out MPS IVB, multiple sulfatase deficiency, and mucolipidoses types II/III are critical as part of enzyme activity testing. Leukocytes or cultured dermal fibroblasts are strongly recommended for enzyme activity testing to confirm screening results. Molecular testing may also be used to confirm the diagnosis in many patients. However, two known or probable causative mutations may not be identified in all cases of MPS IVA. A diagnostic testing algorithm is presented which attempts to streamline this complex testing process

Moment arms about the carpal and metacarpophalangeal joints for flexor and extensor muscles in equine forelimbs

Objective - To determine whether muscle moment arms at the carpal and metacarpophalangeal joints can be modeled as fixed-radius pulleys for the range of motion associated with the stance phase of the gait in equine forelimbs. Sample Population - 4 cadaveric forelimbs from 2 healthy Thoroughbreds. Procedure - Thin wire cables were sutured at the musculotendinous junction of 9 forelimb muscles. The cables passed through eyelets at each muscle's origin, wrapped around single-turn potentiometers, and were loaded. Tendon excursions, measured as the changes in lengths of the cables, were recorded during manual rotation of the carpal (180° to 70°) and metacarpophalangeal (220° to 110°) joints. Extension of the metacarpophalangeal joint (180° and 220°) was forced with an independent loading frame. Joint angle was monitored with a calibrated potentiometer. Moment arms were calculated from the slopes of the muscle length versus joint angle curves. Results - At the metacarpophalangeal joint, digital flexor muscle moment arms changed in magnitude by ≤ 38% during metacarpophalangeal joint extension. Extensor muscle moment arms at the carpal and metacarpophalangeal joints also varied (≤ 41% at the carpus) over the range of joint motion associated with the stance phase of the gait. Conclusions and Clinical Relevance - Our findings suggest that, apart from the carpal flexor muscles, muscle moment arms in equine forelimbs cannot be modeled as fixed-radius pulleys. Assuming that muscle moment arms at the carpal and metacarpophalangeal joints have constant magnitudes may lead to erroneous estimates of muscle force in equine forelimbs.</p