Juvenile Gaucher Disease (Type III/Subacute Neuronopathic)

Less than 1:100,000

Autosomal recessive with no sex predominance

Panethnic but more common in Northern Sweden and Palestinian town of Jenin

Abnormal platelet functioning and increased risk of bleeding

Respiratory failure

Seizure

Intraoperative blood loss and need for transfusion of PRBC, FFP, and platelets

Perioperative continuation of anticonvulsant therapy and possible need to supplement

GERD and aspiration

Potential presence of restrictive or obstructive lung pathology

Potential presence of pathologic fractures, including vertebrae

Type IIIc disease: Intracardiac calcifications—mitral valve, aortic valve, ascending aorta, aortic arch, and coronary ostia

Variable clinical expression and severity; presents along a continuum.

Systemic involvement often present in all forms of Gaucher disease, including type III:

• Splenomegaly, which may lead to anemia, thrombocytopenia, and leukopenia.

• Platelet dysfunction independent of splenic involvement.

• Decrease in coagulation factors.

• Hepatomegaly.

• Skeletal involvement, including bone marrow infiltration, osteonecrosis/osteoporosis, and pathologic fractures.

Systemic involvement more common in type III disease:

• Pulm involvement, including interstitial lung disease, pulm Htn, or hepatopulmonary syndrome.

• GERD with chronic aspiration.

Specific to type III disease:

• Slowly progressive neurologic symptoms.

• Supranuclear horizontal gaze palsy is pathognomonic sign.

• Seizures may be present.

• Oculomotor apraxia.

• Three subtypes:

  • Type IIIa: Myoclonus; dementia

  • Type IIIb: Early onset of isolated horizontal supranuclear gaze palsy; aggressive systemic illness

  • Type IIIc: Intracardiac calcifications—mitral valve, aortic valve, ascending aorta, aortic arch, and coronary ostia

Autosomal recessive deficiency of the lysosomal enzyme acid beta-glucosidase.

Results in accumulation of glucosylceramide in various tissues, most often lysosomes of macrophages.

• Can lead to macrophage clumping in liver, spleen, and bone marrow.

• Hypersplenism may result in anemia, thrombocytopenia, and leukopenia.

• May also accumulate in lungs, skin, conjunctiva, kidneys, and heart.

Specific to type III (juvenile Gaucher):

• Most common mutation is a variant of L444P, but other missense/null mutations may occur.

• Type IIIa: No specific mutation.

• Type IIIb: Predominantly homozygous mutation of L444P.

• Type IIIc: Homozygous mutation of D409H.