Mucolipidosis II presenting as severe neonatal hyperparathyroidism.
Mucolipidosis II (ML II or I-cell disease ) (OMIM 252500) is an autosomal recessive lysosomal enzyme targeting disorder that usually presents between 6 and 12 months of age with a clinical phenotype resembling Hurler syndrome and a radiological picture of dysostosis multiplex. When ML II is severe enough to be detected in the newborn period, the radiological changes have been described as similar to hyperparathyroidism or rickets. The biological basis of these findings has not been explored and few biochemical measurements have been recorded. We describe three unrelated infants with ML II who had radiological features of intrauterine hyperparathyroidism and biochemical findings consistent with severe secondary neonatal hyperparathyroidism (marked elevation of serum parathyroid hormone and alkaline phosphatase levels). The vitamin D metabolites were not substantially different from normal and repeatedly normal calcium concentrations excluded vitamin D deficiency rickets and neonatal severe hyperparathyroidism secondary to calcium-sensing receptor gene mutations (OMIM 239200). The pathogenesis of severe hyperparathyroidism in the fetus and newborn with ML II is unexplained. We hypothesize that the enzyme targeting defect of ML II interferes with transplacental calcium transport leading to a calcium starved fetus and activation of the parathyroid response to maintain extracellular calcium concentrations within the normal range.


CONCLUSIONS
Newborns with mucolipidosis II can present with radiological and biochemical signs of hyperparathyroidism. Awareness of this phenomenon may help in avoiding diagnostic pitfalls and establishing a proper diagnosis and therapy.
Unger
Sheila
S
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada. Sheila.Unger@hospvd.ch
Paul
David A
DA
Nino
Michelle C
MC
McKay
Charles P
CP
Miller
Stephen
S
Sochett
Etienne
E
Braverman
Nancy
N
Clarke
Joe T R
JT
Cole
David E C
DE
Superti-Furga
Andrea
A
D001851:Bone Diseases, Metabolic / Q000150:complications* / Q000000981:diagnostic imaging; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000175:diagnosis*; D007231:Infant, Newborn; D008297:Male; D009081:Mucolipidoses / Q000175:diagnosis* / Q000503:physiopathology; D011859:Radiography