Mucolipidosis

Mucolipin, also known as mucolipin 1 or mucolipidin (encoded by the MCOLN1 gene), is a TRP channel-related membrane protein, most probably residing in intracellular membranes. Is defective in mucolipidosis type IV disease, a developmental neurodegenerative disorder characterized by lysosomal storage disorder and abnormal endocytosis of lipids. The fimction of mucolipin is unknown. 

The term mucolipidosis was introduced to denote diseases that combined features common to both mucopolysaccharidoses and sphingolipidoses (Chapter 24). Three mucolipidoses are listed in Table 48—7. In sialidosis (mucolipidosis I, ML-I), various oligosaccharides derived from glycoproteins and certain ganglio-sides can accumulate in tissues. I-cell disease (ML-II)... 

Methylmalonic aciduria (Bi2-reslstant) Mucolipidosis II (I-cell disease) Nlemann-Plck disease Sandhoff disease... 

Mucolipidosis type 11 (I-cell disease) Mucolipidosis type IIIA (pseudo-Hurler s)... 

Pseudo-Hurler polydystrophy (mucolipidosis III, ML-III) is related to l-cell disease, but cells of these patients retain some activity of the deficient enzyme. 

The answer is D. As this patient ages, a variety of skeletal defects and short stature that are consistent with a lysosomal storage disease (mucolipidosis), either I-cell disease or pseudo-Hurler polydystrophy, are developing. Both diseases arise from a deficiency of an enzyme involved in synthesis of the Man-6-P marker on lysosomal enzymes. Such misaddressed proteins are secreted rather than trafficked to the lysosomes. The degradative function of lysosomes is impaired as a result and the organelles tend to accumulate waste products (hence, the term storage disease ). It is these inclusion bodies or dense structures that would be visible by microscopic examination of the patient s cells in a biopsy specimen. 

Fig. 4.1.9 Electrophoresis pattern of different types of MPS (indicated beneath the corresponding band). Standards (STD) and normal controls (N) were also run on each gel. GAGs are labeled on the left side of the figure. The picture was kindly provided by Dr. E Buerger, Metabolic Center Heidelberg, Germany. GM1 GM1-gangliosidosis, MSD multiple sulfatase deficiency ML II mucolipidosis II, LZ loading zone of the gel...

Some hereditary diseases are characterized by lack of two or more lysosomal enzymes. In I-ceII disease (mucolipidosis II), which resembles the Hurler syndrome, at least ten enzymes are absent or are present at much reduced levels.350,361 The biochemical defect is the absence from the Golgi cisternae of the N-acetylglucosaminyl phosphotransferase that transfers P-GlcNAc units from UDP-GlcNAc onto mannose residues (Eq. 20-22) of glycoproteins marked for use in lysosomes. 

Besley GTN, Broadhead DM, Nevin NC, et al. Prenatal diagnosis of mucolipidosis II by early amniocentesis. Lancet 335 1164-1165,1990. 

Falik-Zaccai TC, Zeigler M, Bargal R, et al. Mucolipidosis III type C first-trimester biochemical and molecular prenatal diagnosis. Prenat Diagn 23 211-214,2003. 

Jansen SM, Groener JEM, Poorthuis VJHM Lysosomal phospholipase activity is decreased in mucolipidosis II and III fibroblasts. Biochim Biophys Acta 1436 363-369,1999. 

Mueller OT, Honey NK, Little LE Mucolipidosis II and III. The genetic relationships between two disorders of lysosomal enzyme biosynthesis./ Clin Invest 72 1016-1023,1983. 

Poenaru L, Castelnau L,Tome F, et al. A variant of mucolipidosis II. Clinical, biochemical and pathological investigations. Ear J Pediatr 147 321-327,1988. 

Raas-Rothschild A, Bargal R, Goldman O, et al. Genomic organization of the UDP-Ar-acetyl-glucosamine-l-phosphotransferase J subunit (GNPTAG) and its mutations in mucolipidosis Ifi. J Med Genet 4l e52,2004. 

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