Lysosomal storage disorders: Pathology review

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Lysosomal storage disorders: Pathology review



Lysosomal storage disorders: Pathology review

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A 3-year-old boy is being evaluated for developmental delay. He recently learned to sit up on his own; however, he is unable to stand up without support. His past medical history is significant for recurrent upper respiratory infections. His family is of Ashkenazi Jewish descent. Physical examination shows coarse facial features, kyphoscoliosis, and restricted joint mobility. Abdominal examination reveals hepatosplenomegaly. Ophthalmic examination reveals corneal clouding. A genetic condition is suspected. Which of the following intracellular processes are defective considering the most likely diagnosis? 


At the pediatric clinic, Abigail, a 5-month-old girl of Ashkenazi Jewish descent, is brought in by her parents because of recurring episodes of seizures, which started about a month ago. Her parents have also noticed that Abigail startles easily at loud noises. Physical examination reveals a low muscle tone with exaggerated reflexes. Upon palpation of the abdomen, the liver and spleen are of normal size. On ophthalmologic examination, a cherry red spot is found on the maculae of both eyes. Next in the clinic, there’s 2-year-old Harry. According to his mother, he recently stopped walking and speaking in sentences, and instead started crawling and babbling again. On further questioning, his mother mentions that Harry seems to have a hard time sitting still and often shows aggressive behavior. Physical examination reveals a prominent forehead, a nose with a flattened bridge and flared nostrils, an enlarged tongue, and thickened lips. On ophthalmologic examination, no corneal clouding is observed.

Based on the initial presentation, both Abigail and Harry seem to have some form of lysosomal storage disorder. These are a group of inherited metabolic disorders that result in the inability to break down certain substances in lysosomes, causing them to build up, and ultimately leading to cell damage and death. Lysosomal storage disorders include sphingolipidoses, caused by the accumulation of a certain type of lipids called sphingolipids. Mucopolysaccharidoses are caused by the accumulation of a type of complex sugars called mucopolysaccharides or glycosaminoglycans. Finally, there’s also mucolipidoses, which are caused by the accumulation of both sphingolipids and mucopolysaccharides.

Okay, let’s start with sphingolipidoses! Gaucher disease is the most common lysosomal storage disorder. It is caused by a mutation in the GBA gene, which codes for the enzyme glucocerebrosidase, also known as beta-glucosidase. For your exams, remember that Gaucher disease is autosomal recessive, meaning that an individual needs to inherit two copies of the mutated gene, one from each parent, to develop the condition. Another thing to note is that Gaucher disease is more common in those of Ashkenazi Jewish heritage.


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