mucolipidos

Mucolipidoses are a group of rare inherited lysosomal storage disorders characterized by defective trafficking of lysosomal enzymes to lysosomes, leading to the accumulation of undigested substrates within cells. They overlap clinically with mucopolysaccharidoses and other storage diseases, reflecting broad disturbances in cellular digestion and trafficking rather than a single substrate.

Genetics and causes: Most mucolipidoses are inherited in an autosomal recessive manner. The two major infantile forms are mucolipidosis II (I-cell disease) and mucolipidosis III (pseudo-Hurler polydystrophy). These conditions typically arise from mutations in GNPTAB or GNPTG, which encode components of the enzyme that tags hydrolytic enzymes with mannose-6-phosphate for lysosomal delivery. A distinct entity, mucolipidosis IV, results from biallelic mutations in MCOLN1, encoding mucolipin-1, a lysosomal ion channel involved in endolysosomal function.

Clinical features: I-cell disease usually presents in infancy with failure to thrive, coarse facial features, skeletal abnormalities, and developmental delay. ML III tends to present later with milder skeletal and growth disturbances but shares some similar organ involvement. ML IV is characterized by significant neurodevelopmental impairment and progressive eye involvement, among other features.

Diagnosis: Diagnosis relies on a combination of clinical assessment, biochemical testing showing misrouting of lysosomal enzymes (elevated serum lysosomal enzyme activities in some forms), and confirmation by genetic testing. Histology may reveal characteristic inclusion bodies in certain cells.

Management and prognosis: There is no cure; treatment is supportive and multidisciplinary, focusing on growth, development, nutrition, vision and hearing, orthopedic care, and symptom management. Prognosis varies by type, with I-cell disease typically most severe and ML IV having substantial but more variable impairment.