Mucolipidosis type IIIA is one of the lysosomal storage diseases. Lysosomes are membrane bound organelles, which break down fats and carbohydrates within cells. This catabolism requires a large number of hydrolytic enzymes inside the lysosomes. ML IIIA is a targeting defect, wherein the enzymes that need to move into the lysosome, lack the signal necessary for this entry. Thus, they cannot get into the lysosomes, and remain outside it. The lysosomal processes are therefore, affected, and the lipids and polysaccharides, instead of being broken down, get accumulated in different tissues of the body.

The clinical features of this disease are similar to Mucolipidosis type II, and include multiple bone formation abnormalities, especially in the hip, scoliosis, progressive joint stiffness, delayed physical and mental development, hearing loss, swollen liver and spleen, and occasionally heart disease in the aortic valve. In addition, ML III also shows increased acne, enlarged tongue, and a clouding of the cornea due to accumulation of lipid substances. The disease, on the whole is milder in its presentation, and has a later onset at 2-4 years of age, as compared to ML II. Increased activity of lysosomal enzymes in the serum, and decreased activity of N-acetylglucosamine-1-phosphotransferase in cultured fibroblasts from skin biopsies are laboratory findings of the disorder. No definitive cure is available for ML III. Surgical intervention may be required to treat some of the symptoms. Recently, biphosphonate drugs, such as IV Pamidronate, have been developed to treat the skeletal symptoms of the disorder.

The genetic basis of ML III is considered to be heterogeneous, with many classes of mutations in the processing pathways of lysosomal enzymes. The major gene implicated in the disorder is GLcNAc-phosphotransferase, which codes for the UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine 1-phosphotransferase (phosphotransferase). This enzyme is involved in the synthesis of the mannose-6-phosphate tag, which has to be present on the lysosomal enzymes, in order to be targeted to the lysosome. Mutations in the gene lead to defects in the addition of these tags causing defective lysosomal targeting of many lysosomal enzymes, and the subsequent clinical features of mucolipidosis.