HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 59, Number 3, August 13, 2002 Supplementary Data Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Altarescu, G. Articles by Schiffmann, R. Search for Related Content PubMed PubMed Citation Articles by Altarescu, G. Articles by Schiffmann, R. Related Collections Metabolic disease (inherited) All Pediatric Developmental disorders All Genetics

The neurogenetics of mucolipidosis type IV

From the Developmental and Metabolic Neurology Branch (Drs. Altarescu, Sun, Moore, Wiggs, Frei, Gupta, Goldin, and Schiffmann, and C.R. Kaneski), Speech Language Pathology Section, Rehabilitation Medicine Department (B.I. Solomon), Diagnostic Radiology Department, Warren G. Magnuson Clinical Center (Dr. Patronas), and National Eye Institute (Dr. Smith), National Institutes of Health, Bethesda, MD; Harvard Institute of Human Genetics (Dr. Slaugenhaupt), Harvard Medical School, Boston, and Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA; and North Trent Genetics Service (Dr. Quarrell), Sheffield Children’s Hospital, UK.

Address correspondence and reprint requests to Dr. Raphael Schiffmann, National Institutes of Health, 9000 Rockville Pike, Bldg. 10, Rm. 3D03, Bethesda, MD 20892-1260; e-mail: rs4e{at}nih.gov

Background: Mucolipidosis type IV (MLIV) is an autosomal recessive disease caused by mutations in the MCOLN1 gene that codes for mucolipin, a member of the transient receptor potential (TRP) gene family.

Objective: To comprehensively characterize the clinical and genetic abnormalities of MLIV.

Methods: Twenty-eight patients with MLIV, aged 2 to 25 years, were studied. Ten returned for follow-up every 1 to 2 years for up to 5 years. Standard clinical, neuroimaging, neurophysiologic, and genetic techniques were used.

Results: All patients had varying degrees of corneal clouding, with progressive optic atrophy and retinal dystrophy. Twenty-three patients had severe motor and mental impairment. Motor function deteriorated in three patients and remained stable in the rest. All had a constitutive achlorhydria with elevated plasma gastrin level, and 12 had iron deficiency or anemia. Head MRI showed consistent characteristic findings of a thin corpus callosum and remained unchanged during the follow-up period. Prominent abnormalities of speech, hand usage, and swallowing were also noted. Mutations in the MCOLN1 gene were present in all patients. Correlation of the genotype with the neurologic handicap and corpus callosum dysplasia was found.

Conclusions: MLIV is both a developmental and a degenerative disorder. The presentation as a cerebral palsy-like encephalopathy may delay diagnosis.

This article has been cited by other articles:

				E. Goldin, R. C. Caruso, W. Benko, C. R. Kaneski, S. Stahl, and R. Schiffmann Isolated Ocular Disease Is Associated with Decreased Mucolipin-1 Channel Conductance Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 3134 - 3142. [Abstract] [Full Text] [PDF]

				E. E. Benarroch TRP channels: Functions and involvement in neurologic disease Neurology, February 19, 2008; 70(8): 648 - 652. [Full Text] [PDF]

				B. Nilius, G. Owsianik, T. Voets, and J. A. Peters Transient Receptor Potential Cation Channels in Disease Physiol Rev, January 1, 2007; 87(1): 165 - 217. [Abstract] [Full Text] [PDF]

				J. J. Jennings Jr., J.-h. Zhu, Y. Rbaibi, X. Luo, C. T. Chu, and K. Kiselyov Mitochondrial Aberrations in Mucolipidosis Type IV J. Biol. Chem., December 22, 2006; 281(51): 39041 - 39050. [Abstract] [Full Text] [PDF]

				L. Schaheen, G. Patton, and H. Fares Suppression of the cup-5 mucolipidosis type IV-related lysosomal dysfunction by the inactivation of an ABC transporter in C. elegans Development, October 1, 2006; 133(19): 3939 - 3948. [Abstract] [Full Text] [PDF]

				K. Venkatachalam, T. Hofmann, and C. Montell Lysosomal Localization of TRPML3 Depends on TRPML2 and the Mucolipidosis-associated Protein TRPML1 J. Biol. Chem., June 23, 2006; 281(25): 17517 - 17527. [Abstract] [Full Text] [PDF]

				F. M. Hantash, S. C. Olson, B. Anderson, A. Buller, R. Chen, B. Crossly, W. Sun, and C. M. Strom Rapid One-Step Carrier Detection Assay of Mucolipidosis IV Mutations in the Ashkenazi Jewish Population J. Mol. Diagn., May 1, 2006; 8(2): 282 - 287. [Abstract] [Full Text] [PDF]

				S. Treusch, S. Knuth, S. A. Slaugenhaupt, E. Goldin, B. D. Grant, and H. Fares Caenorhabditis elegans functional orthologue of human protein h-mucolipin-1 is required for lysosome biogenesis PNAS, March 30, 2004; 101(13): 4483 - 4488. [Abstract] [Full Text] [PDF]

				M. K. Raychowdhury, S. Gonzalez-Perrett, N. Montalbetti, G. A. Timpanaro, B. Chasan, W. H. Goldmann, S. Stahl, A. Cooney, E. Goldin, and H. F. Cantiello Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel Hum. Mol. Genet., March 15, 2004; 13(6): 617 - 627. [Abstract] [Full Text] [PDF]

				J. K. Inlow and L. L. Restifo Molecular and Comparative Genetics of Mental Retardation Genetics, February 1, 2004; 166(2): 835 - 881. [Abstract] [Full Text] [PDF]

				S. Bonavita, A. Virta, N. Jeffries, E. Goldin, G. Tedeschi, and R. Schiffmann Diffuse Neuroaxonal Involvement in Mucolipidosis IV as Assessed by Proton Magnetic Resonance Spectroscopic Imaging J Child Neurol, July 1, 2003; 18(7): 443 - 449. [Abstract] [PDF]