The natural history and osteodystrophy of mucolipidosis types II and III

Abstract

Aim: 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.

Conclusion: 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.

Figures

Fig 1

Radiograph of pelvis and femurs in a neonate with Mucolipidosis Type II – showing features of neonatal hyperparathyroidism including periosteal cloaking and destructive bone lesions,

Fig 2

Radiograph of pelvis and femurs in a 3 year old with Mucolipidosis type II showing over-modelling of the proximal end of the femur leading to coxa valga or “shepherd’s crook deformity”. The lower third of the ilia have become progressively hypoplastic and resorbed.

Fig. 3

Radiograph of hands and wrists in four affected with ML II/III aged (a) 4 yrs., (b) 16 yrs., (c) 18 yrs., (d) 19 yrs. showing progressive osteolysis of carpal centres, proximal metacarpals and distal forearm bones.

Fig. 3

Radiograph of hands and wrists in four affected with ML II/III aged (a) 4 yrs., (b) 16 yrs., (c) 18 yrs., (d) 19 yrs. showing progressive osteolysis of carpal centres, proximal metacarpals and distal forearm bones.

Fig. 4

Radiograph of pelvis and proximal femurs in four affected with ML II/III aged (a) 4 yrs., (b) 16 yrs., (c) 18 yrs., (d) 19 yrs. showing progressive dysplasia/resorbtion of the low third of the ilia femoral heads and femoral necks.

Fig. 4

Radiograph of pelvis and proximal femurs in four affected with ML II/III aged (a) 4 yrs., (b) 16 yrs., (c) 18 yrs., (d) 19 yrs. showing progressive dysplasia/resorbtion of the low third of the ilia femoral heads and femoral necks.