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Lysosomal Storage Disorders

May 18, 2023

Lysosomal Storage Disorders

The hallmark of lysosomal storage diseases, which are inherited metabolic disorders brought on by enzyme shortages, is an abnormal accumulation of different toxins in the body's cells. There are about 50 of these illnesses in all, and they can affect various organs like the heart, skeleton, brain, skin, and central nervous system. There are still being discovered new lysosomal storage diseases. There is currently no approved treatment for many lysosomal storage diseases, while scientific trials on potential remedies for some of these illnesses are ongoing.

Important Lysosomal Storage Disorders

DiseaseCherry red spotVisceromegalySkeletal involvement
Gaucher diseaseAbsentPresentPresent
Niemann Pick diseasePresentPresentAbsent
GM1 gangliosidosisPresentPresentPresent
Tay Sach diseasePresentAbsentAbsent

Read this blog further to get a quick overview of this important topic for PEDIATRICS and ace your NEET PG/NExT exam preparation.

Gaucher Disease

It is the most common lysosomal storage disorder seen in children. There is  Deficiency of enzyme Glucocerebrosidase due to which there is Accumulation of glucocerebrosides in various cells of the body which leads to Accumulation in cytoplasm gives cytoplasm “Crumpled tissue paper” appearance.

 Gaucher cells -Gaucher cells accumulate in various parts of the body.Accumulation in the spleen leads to Splenohepatomegaly. Accumulation in bone leads to Pancytopenia causing bone pains and pathological fracture and Accumulation in nervous system leads to Neurological involvement .

Clinical features of Gaucher disease

Some children may remain asymptomatic, But children with symptoms usually have

  • Splenohepatomegaly: One of the causes of massive splenomegaly that it can even cross the umbilicus
  • Pancytopenia: Anemia; easy fatigability, lassitude, lethargy
  • Leukopenia: Recurrent infections
  • Thrombocytopenia: Bleeding manifestations
  • Bone pains and pathological fractures
  • Lytic lesions of long bones known as Erlenmeyer flask bone deformity
  • Neuronal involvement may or may not be present. Neurological involvement is absent in type 1. Type 2 & 3 can have some neurological involvement

Diagnosis of Gaucher disease

  • Characteristic clinical presentation
  • Bone marrow aspiration ± biopsy: Gaucher cells with characteristic “Crumple tissue paper” appearance of cytoplasm 
  • Demonstrate the deficient glucocerebrosidase enzyme activity in the leucocytes or skin fibroblast
  • X-ray of long bones: which shows us  Erlenmeyer flask deformity 

Treatment of Gaucher disease 

  • Enzyme replacement therapy is available -With this therapy, organomegaly decrease, pancytopenia improves and these children can have a near normal life. Enzyme replacement therapy is costly so funds are required to manage it
  • Supportive care -These children require regular blood transfusion, Treatment of infections and For bleeding, give platelets 
  • Hematopoietic stem cell transplantation plays a potential role

Diseases for which Enzyme Replacement therapy is available

  • Gaucher disease
  • Type II glycogen storage disorder/Pompe disease
  • Mucopolysaccharidosis Type I (Hurler disease), Type II (Hunter disease) and Type VI (Maroteaux-Lamy syndrome)
  • Fabry disease 
  • Niemann Pick disease (Recently available)
  • Morquio disease

Niemann Nick Disease                                               

There are 3 types of Niemann Pick disease

  • Type A and B results from deficiency of enzyme acid sphingomyelinase for which gene is encoded on chr. 11. It has autosomal recessive inheritance 
  • Type A Niemann Pick disease - It is a rapidly progressive neurodegenerative disorder. Clinical features are Hepatosplenomegaly, Lymphadenopathy, and death usually by 3 years of age
  • Type B Niemann Pick disease - It is a non-neuronopathic form. This form can be seen in children as well as adults. Hepatosplenomegaly is usually seen. Cherry red spot is present. Chest X-ray shows pulmonary infiltrates in the form of diffuse reticular opacities 
  • Type C Niemann Pick disease - It is a neuronopathic disorder where neurological features are seen that results from defective cholesterol transport. It often presents with prolonged neonatal jaundice. Recently enzyme replacement therapy for Niemann pick disease is available

GM1 Gangliosidosis

It is an autosomal recessive disorder .It is due to deficiency of enzyme β-galactosidase. As a result, GM1 ganglioside accumulates in various cells of the body including neurological system. It can have infantile/juvenile/adult presentation .Infantile type is the most severe type with onset before 6 months and death in the early childhood. It can also present with hydrops fetalis. Clinical presentation: Splenohepatomegaly, bony manifestations, neuro regression, cherry red spot, and death in early childhood

Tay Sach Disease

It is due to deficiency of enzyme Hexosaminidase. It is a neurodegenerative disorder with progressive CNS dysfunction. The most common and most severe form of Tay Sach disease is infantile. Clinical presentation: Reduced vision, exaggerated startle, neuroregression, seizures and death usually occur in early childhood. Splenomegaly is usually not present in Tay Sach disease. It has an autosomal recessive inheritance 

Mucopolysaccharidosis (MPS)                      

TypeNameEnzyme deficient
IHurler disease(more severe)/Scheie disease (milder severe)α-L-Iduronidase
IIHunter diseaseIduronate Sulfate sulfatase
IIISanfilippo diseaseHeparin-S-Sulfamidase
IVMorquio diseaseN-acetyl-galactosamine Sulfate Sulfatase
VIMaroteaux-Lamy diseaseAryl Sulfatase B

Clinical features of Hurler disease

  • Child with coarse facies i.e., puffy looking facies, periorbital puffiness, depressed nose bridge, prominent philtrum, protruding tongue
  • Intellectual disability/mental retardation
  • Corneal clouding
  • Hepatosplenomegaly
  • Copious nasal discharge, airway problems
  • Bony abnormalities: Dysostosis multiplex - proximal tapering of metacarpals or bullet shaped metacarpals, anterior beaking of the vertebral body, J shaped Sella turcica 
  • Cardiac abnormalities

Clinical features of other Mucopolysaccharidosis 

DiseaseClinical features
Hunter diseaseSame clinical features as Hurler disease but there is no corneal opacity
San Filippo diseaseMainly presents with Intellectual disability/mental retardation, behavioral problems
Morquio diseaseBony abnormalities are most prominent
Maroteaux-Lamy diseaseSame as  Morquio disease + Coarse facies + Visceromegaly 

Inheritance pattern

  • All type of MPS have autosomal recessive inheritance except Type II MPS (Hurler disease) which has X-linked recessive inheritance 
  • Most of the lysosomal storage disorders have autosomal recessive inheritance except Fabry disease which has X-linked recessive inheritance 

Fabry Diseases

Basic defect: Deficiency of enzyme α-Galactosidase. It has X-linked recessive inheritance. Most characteristic clinical feature: Angiokeratoma - reddish pinpoint spots which are non-blanching and present mainly on bathing trunk area i.e., it is present between umbilicus and knees most densely. Other clinical feature include Hyperhidrosis or excessive sweating, Corneal or lenticular opacities, Acroparaesthesias, Pain which is severe and debilitating due to involvement of nerves, Vascular disease of brain/heart/kidney develops. Enzyme replacement therapy is now available for Fabry disease

Lesch Nyhan Syndrome

Basic defect is Deficiency of HGPRT (Hypoxanthine Guanine Phospho Ribosyl Transferase) enzyme. This enzyme helps in recycling of the building blocks of DNA and RNA. It has an X-linked recessive inheritance.

Clinical features

  • It can be asymptomatic at birth 
  • Subsequently, Developmental delay and other neurological features like dystonia, dysarthria, and spasticity 
  • Self-Injury/Self-Mutilation


  • Increased level of uric acid, due to excess turn over of purine, pyrimidine, DNA, RNA
  • There is deficiency of HGPRT enzyme


  • Because uric acid levels are very high use
    • Allopurinol
    • Alkalinization 
    • High fluid intake

Menke Disease           

It is caused by mutation in ATP 7A gene.Mutation in ATP 7B gene cause Wilson disease. ATP 7A gene is a gene encoding copper transporting ATPase. So, there is impaired copper metabolism and less copper levels are found in liver and brain but high copper levels are found in fibroblasts and enterocytes 

Clinical features

  • Progressive cerebral degeneration or neurodegeneration
  • Seizures
  • Feeding difficulties
  • Failure to thrive
  • Hypothermia
  • Apnea
  • Characteristic hair abnormalities: Wooly or fuzzy hair
    • On hair microscopy: Trichorrhexis nodosa i.e., breakages in the hair shaft 
      • Pilli torti i.e., twisting of hairs at different places
  • It has poor prognosis and in classical form of disease, death usually occurs by 3 years of age 

Wolman Disease 

Basic defect: It is an autosomal recessive disorder.  Mutation in LIPA gene leads to Deficiency of lysosomal acid lipase. Accumulation of triglycerides and cholesterol esters in various cells

Clinical features

  • Hepatosplenomegaly 
  • Jaundice
  • Vomiting
  • Diarrhea 


  • Plain X-ray abdomen: Bilateral adrenal gland calcifications is seen

This is everything that you need to know about lysosomal storage disorder for your PEDIATRICS PREPARATION. For more interesting and informative blog posts like this download the PrepLadder App and keep reading our blog!

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