Question

A patient's fibroblast cells contain "inclusion bodies," which are lysosomes packed with undigested material. What are possible cellular bases that cause lysosomal accumulations of undigested material?

Answer 1

Fibroblasts are main cells in connective tissues which are mainly seen in epithelium and endothelium. They are spindle shaped cells which helps in the synthesis of extra cellular matrix, collagen etc. They give a structural frame work to our body. They also involve in would healing and tissue repair.

Lysosomes are membrane bound organelle in mammalian body which are acidic in nature. Their primary function is the endocytic degradation of autophagic, phagocytic substrates like membranes, proteins and also RNA, DNA also. Thus they are the disposing area of cellular wastes. They breakdown macromolecules into its simple forms. They contain enzymes like protease, lipase, nuclease etc..

Inclusion bodies are cytoplasmic aggregates which are accumulations of undigested materials mainly proteins which are stainable and can be watched through microscope. They mainly occurs in humans due to a virus attack or by any genetic disorder or mutation. They are specific for some diseases. Nowadays, inclusion bodies are vital in the identification of underlying diseases.
When an infection occurs or a mutation happens, the affected mRNA translates a protein which never undergo modifications and condensation, when reaches to lysosomes causing formation of inclusion bodies. There are different types of inclusion bodies- physiological inclusion bodies, infection inclusion bodies etc.. The inclusion bodies of lysosomes in nerve tissues are called lipofuscin.

Lysosomal storage diseases (LSD) are metabolic disorders which causes mutation mainly in lysosomal hydrolases which are used in degradation,
Lysosomal membrane protein mutation causing trafficking issues and non lysosomal mutation which may cause indirect problems in lysosome. Recent studies shows that this LSD can be effectively reduced by induction of exocytosis of lysosomes. That is one major treatment.

SO, THE PATIENT HERE IS SUFFERING FROM A LYSOSOMAL STORAGE DISEASE. Here, lysosomes in fibroblasts are accumulated with undigested proteins whoch shows he is having either a mutation or genetic disease.otherwise a viral infection. If it is a lipid accumulation, then it leads to lysosome dysfunction and eventually causes cell death.

The symptoms of the patient reveals that he might be having an inherited disorder called MUCOLIPIDOSIS-ll which is a metabolic fatal disease. It is caused due to the deficiency of GlcNac-phosphotransferase(UDP-N-acetylglucosamine:lysosomal-enzyme N-acetylglucosaminephosphotransferase), which helps in synthesis of mannose-6- phosphate marker for lysosomes in fibroblasts. It causes acid hydolase enzymes in lysosomes to get inactivated and it leads to undigested materials accumulated in lysosomes which can be termed as inclusion bodies.

They are mainly seen in skin fibroblasts. On experimentation, the pH and the accumulation of particles were three fold higher in lysosomes affected with ML-II. In an experiment, supplimentation of enzymes taken from normal lysosome into infected lysosomes showed disapperance of inclusion bodies and other impariments.

Thus the main cause of inclusion bodies in lysosomes are the mutations or infections causing impairment of lysosomal enzymes.