Gaucher's disease

Question 1

What is Gaucher’s disease?

Answer 1

• An autsomal recessive deficiency of acid Beta glucocerebrosidase
• most common glycogen storage disease
• 1 in 40,000 incidence
• most common in **Ashkenazi Jewish origin **

Question 2

what is the pathophysiology of Gaucher’s disease?

Answer 2

• enzyme deficiency leads to disturbances in cell metabolism with accumulations of Sphingolipids in the
  
  • liver
  • spleen
  • Bone marrow

Question 3

What is the classification of Gaucher’s disease?

Answer 3

• Type 1 - Beta glucocerebrosidase deficency- most common
  
  • adult type
  • easy bruising
  • Anaemia , Fx
  • treatable w enzyme replacement therapy ( fatal if enzyme subsitute is not given)
• Type 2 ( infantile)
  
  • Lethal by age 3
  • brain and organ involvement
  • untreated
• Type 3
  
  • ​onset in teens
  • thrombocytopenia, anaemia, enlarged liver
  • fx
  • gradual brain involvement
  • type 3 clinical diverse
  • non CNS respond well to enzymes

Question 4

What are the manifestations of Gaucher’s disease?

Answer 4

• Fatigue
• prolonged bleeding
• fever, chills, sweating
• seizure
• developmental delay

Orthopaedics

• Bone fractures/osteomyelitis
• joint pain/contractures
• bone necrosis/osteonecrosis

Question 5

What are the signs of gaucher’s disease?

Answer 5

• Abnormal skin bruising
• Hepatosplenomegaly
• Cardiac murmur
• bone deformities
  
  • 80% distal femur/ proximal tibia
  • joint contractures
  • pathological fx

Question 6

Symtpoms of Gaucher’s disease?

Answer 6

Systemic

• Fatigue ( anaemia)
• Prolonged bleeding ( thrombocytopenia)
• Fever, chills, sweats ( infection)
• Seizures, developmental delay ( CNS involvment)

Ortho

• Bone pain ( fractures, osteomyelitis)
• joint pain or contractures
• bone crisis ( osteonecrosis)

Question 7

What is seen in the labs with a pt with Gaucher’s disease?

Answer 7

• Anaemia
• Thrombocytopenia
• Dx confirmed with elevated plasma levels of Glucocerebrosides

Question 8

What does histology show on gaucher’s disease?

Answer 8

• bone marrow aspirate shows a giant binucleate storage cell filled with glucocerebrosides
• which accumulate due to deficiency of Beta- glucocerebrosides

Question 9

What is seen on imaging of Gaucher’s disease?

Answer 9

Xrays

• Cardiac enlargement
• pathological fx
• osteonecrosis
• abnormal bone remodelling
• Osteopenia
• ‘Erlenmeyer flask’ deformity of the distal femur- see pic

​MRI/CT

• chronic vasucular insult in osteonecrosis in prox/distal femur/proximal tibia

Question 10

What is the tx of Gaucher’s disease?

Answer 10

Non operative

• observation and support therapy
  
  • for non affected pts ( normal bloods/xrays)
• enzyme replacement therapy
  
  • ​all children and asymptomatic pts
  • not affective in type 2 gaucher’s disease
  • imiglucerase
  • veraglucerase alfa
• ​Substrate reduction therapy
  
  • ​less severely affected pts that can’t tolerate enzyme replacment therapy
  • miglustat

Surgery

• Bone marrow transplant
  
  • ​if reformed early maybe curative

Question 11

What is the tx of fx mx in a pt with Gaucher’s disease?

Answer 11

• preop optimisation with enzyme therapy is critical
• availiability of additional blood, clotting products, and plaletes due to increased bleeding risk
• anaeasthetic to maintain oxygenation to prevent bone crisis
• increased risk of infection