The neurogenetics of mucolipidosis type IV.
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.
Developmental and Metabolic Neurology Branch, National Institute of Neurologic Disorders and Stroke/NIH, 9000 Rockville Pike, Building 10, Rm. 3D03, Bethesda, MD 20892-1260, USA.
G
G
Altarescu
M
M
Sun
D F
DF
Moore
J A
JA
Smith
E A
EA
Wiggs
B I
BI
Solomon
N J
NJ
Patronas
K P
KP
Frei
S
S
Gupta
C R
CR
Kaneski
O W
OW
Quarrell
S A
SA
Slaugenhaupt
E
E
Goldin
R
R
Schiffmann
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology; D003937:Diagnosis, Differential; D004569:Electroencephalography; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D009081:Mucolipidoses / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011446:Prospective Studies; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels
C416674:MCOLN1 protein, human; D008565:Membrane Proteins; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels