Heart and Cardiovascular Involvement in Patients with Mucopolysaccharidosis Type IVA (Morquio-A Syndrome).
BACKGROUND
Mucopolysaccharidosis (MPS) IVA is a rare lysosomal storage disorder with multiple skeletal and non-skeletal abnormalities requiring multiple surgical interventions. It is well known that patients with MPS IVA suffer from tachycardia, but cardiac and hemodynamic alterations have not been reported to date. We investigated the cardiovascular and hemodynamic alterations in patients with MPS IVA and developed a possible patho-mechanism for cardiovascular deterioration during anesthesia.


METHODS
In this observational study, serial cardiac examinations were performed in 54 patients with MPS IVA who were followed at the Children's Hospital of the Mainz Medical University (Mainz, Germany) between 1991 and 2014 (follow-up 1-24 years; median 5.8 years). Results were compared with data from a large central European cohort of more than 2000 healthy infants and children.


RESULTS
None of the patients had arterial hypertension, but 4% had evidence of increased pulmonary artery pressure. Patients developed aortic root extension up to 6.9 standard deviations above normal. Left-sided valve leaflet thickening occurred in 26 patients (five with valve disease). Patients had lower left ventricular dimensions (z: -1.02±0.1), lower stroke volumes (z: -2.3±0.17), lower left ventricular mass (z: -1.5±0.21), but higher wall thickness (z: +0.8±0.16), and higher work index (z: +2.5±0.2) compared to healthy control subjects. Cardiac output was preserved by an increase in heart rate of 21%. Sixty % of patients showed impaired diastolic filling; heart rate (99.0±1.8 vs. 92.0±2.1 bpm), age (18.0±1.8 vs. 14.2±1 years), and cardiothoracic ratio (61.6±3.6% vs. 55±4.2%) of these patients were higher compared to those with normal filling.


CONCLUSIONS
The results of this study suggest an age-progressive disproportion of the intra-thoracic organs of patients with MPS IVA, which is accompanied by aortic root extension and thickened left ventricles, with reduced stroke volumes, impaired diastolic filling patterns, and increased heart rates.
Division of Pediatric Cardiology and Congenital Heart Diseases, Center for Diseases in Childhood and Adolescence, Mainz Medical University, Mainz, Germany.
Christoph
C
Kampmann
Division of Pediatric Cardiology and Congenital Heart Diseases, Center for Diseases in Childhood and Adolescence, Mainz Medical University, Mainz, Germany.
Tariq
T
Abu-Tair
Division of Metabolic Diseases (Villa Metabolica), Center for Diseases in Childhood and Adolescence, Mainz Medical University, Mainz, Germany.
Seyfullah
S
Gökce
Division of Metabolic Diseases (Villa Metabolica), Center for Diseases in Childhood and Adolescence, Mainz Medical University, Mainz, Germany.
Christina
C
Lampe
Division of Metabolic Diseases (Villa Metabolica), Center for Diseases in Childhood and Adolescence, Mainz Medical University, Mainz, Germany.
Jörg
J
Reinke
Division of Metabolic Diseases (Villa Metabolica), Center for Diseases in Childhood and Adolescence, Mainz Medical University, Mainz, Germany.
Eugen
E
Mengel
Division of Metabolic Diseases (Villa Metabolica), Center for Diseases in Childhood and Adolescence, Mainz Medical University, Mainz, Germany.
Julia B
JB
Hennermann
Division of Pediatric Cardiology and Congenital Heart Diseases, Center for Diseases in Childhood and Adolescence, Mainz Medical University, Mainz, Germany.
Christiane M
CM
Wiethoff
D000293:Adolescent; D001794:Blood Pressure / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology; D002319:Cardiovascular System / Q000503:physiopathology*; D002648:Child; D005260:Female; D006321:Heart / Q000502:physiology* / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000503:physiopathology*; D064887:Observational Studies as Topic; D011651:Pulmonary Artery / Q000503:physiopathology; D055815:Young Adult