The natural history and osteodystrophy of mucolipidosis types II and III.
OBJECTIVE
To assess the natural history and impact of the secondary bone disease observed in patients with mucolipidosis (ML) II and III.


METHODS
Affected children and adults were ascertained from clinical genetics units around Australia and New Zealand. Diagnoses were confirmed by the National Referral Laboratory in Adelaide. The study encompassed all patients ascertained between 1975 and 2005. Data focussing on biochemical parameters at diagnosis, and longitudinal radiographic findings were sought for each patient. Where feasible, patients underwent clinical review and examination. Examinations included skeletal survey, bone densitometry, and measurement of serum and urine markers of bone metabolism. In a subset of patients, functional assessment using the Pediatric Evaluation and Disability Inventory (PEDI) and molecular analysis of GNPTAB were performed.


RESULTS
Twenty-five patients with mucolipidosis were ascertained over a 30-year period. Morbidity and functional outcomes on living patients were described. Serum calcium and phosphate were normal. All, but one patient, had normal alkaline phosphatase. Serum osteocalcin and urine deoxypyridinoline/creatinine were elevated. Two radiological patterns were observed (i) transient neonatal hyperparathyroidism in infants with ML II and (ii) progressive osteodystrophy in patients with ML intermediate and ML III. Molecular analyses of GNPTAB in nine subjects are reported.


CONCLUSIONS
ML is characterised by a progressive bone and mineral disorder which we describe as the 'osteodystrophy of mucolipidosis'. The clinical and radiographic features of this osteodystrophy are consistent with a syndrome of 'pseudohyperparathyroidism'. Much of the progressive skeletal and joint pathology is attributable to this bone disorder.
David-Vizcarra
Grace
G
Department of Clinical Genetics, The Children's Hospital at Westmead, New South Wales, Australia.
Briody
Julie
J
Ault
Jenny
J
Fietz
Michael
M
Fletcher
Janice
J
Savarirayan
Ravi
R
Wilson
Meredith
M
McGill
Jim
J
Edwards
Matthew
M
Munns
Craig
C
Alcausin
Melanie
M
Cathey
Sara
S
Sillence
David
D
D000293:Adolescent; D001315:Australia; D002648:Child; D002675:Child, Preschool; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D009081:Mucolipidoses / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D009520:New Zealand; D011859:Radiography; D055815:Young Adult