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  • Mucolipidosis type IV (MLIV) is an autosomal recessive inborn error of intracellular membrane trafficking that is associated with lysosomal inclusions in a variety of cell types. An alteration in mucolipin-1, a transmembrane protein of the transient receptor potential channel family, causes MLIV.

  • Most of the patients with MLIV have severe motor developmental delay, corneal clouding, progressive retinal degeneration, and achlorhydria. A few patients are less severely affected and exhibit variable general developmental delay, ataxia, and dysarthria together with the characteristic corneal clouding and retinal dystrophy. Notably absent are dysplastic bone abnormalities and enlargement of organs such as the liver and the spleen.

  • MLIV is pan-ethnic, but most patients are of Ashkenazi-Jewish ancestry, in which the most prevalent mutation occurs at a frequency of approximately 1/100.

  • The mucolipidosis type IV gene, MCOLN1, spans 12,300 base pairs on chromosome 19p13.3 and contains 14 exons. The product of this gene is called mucolipin-1, a 580-amino-acid protein with 6 transmembrane domains. This protein is thought to be a nonselective cation channel or a calcium channel, but its exact function is not yet completely understood.

  • Two mutations, g.5534A→G and g.511-6944del, are present in 95% of all Ashkenazi-Jewish patients. Population-based screening for these mutations is useful for the identification and counseling of MLIV carriers. Identification of mutations in MCOLN1 should be used for prenatal diagnosis.

  • The diagnosis of patients suspected of having MLIV can be strengthened by the finding of elevated blood gastrin. A skin biopsy showing lysosomal inclusions in almost every cell type can assist in the diagnosis. Identifying mutations in the MCOLN1 gene makes the definitive diagnosis.

  • There is no specific treatment for patients with MLIV. A comprehensive rehabilitative approach can significantly improve quality of life.


The first patient with this disorder, a 5.5-month-old Ashkenazi Jewish boy who presented with cloudy corneas and mild developmental delay, was described in 1974 (Berman et al,13). The patient had no dysmorphic facial features or skeletal abnormalities, and the known lysosomal enzymes were normal. The term mucolipidosis type IV (MLIV) was chosen due to the corneal clouding and the presence of multilamellar cytoplasmic inclusions in the liver, conjunctiva, and fibroblasts, similar to those seen in the sphingolipidoses, as well as the presence of single-membrane fibrogranular bodies that are often seen in the mucopolysaccharidoses (Berman et al,13). Subsequently, other MLIV patients were described with the typical severe neurologic disability (Altarescu et al,2; Amir et al,3; Crandall et al,24; Goutieres et al,38; Merin et al,52) Patients with a mild form of the disease also have been reported (Casteels et al,18; Reis et al,62). Early on it was noted that the pathologic intracytoplasmic inclusions were present in virtually every cell in the brain, eye, and other organs (Kenyon et al,42; Tellez-Nagel et al,70), although thus far there has been only ...

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