1. Background

• ceramidase catalyzes the conversion of ceramide to sphingosine and fatty acid

2. Genetic Defect

• genetic defect -> deficiency of ceramidase activity -> accumulation of ceramide primarily in visceral tissues -> cell damage with an inflammatory response -> formation of nodules or granules - the CNS does not appear to be involved
• the nodules can form in the subcutaneous tissue around joints, on the vocal cords, and within the upper airway
• there may be several variant forms ranging from mild to severe

1. Musculoskeletal Manifestations

• painful joint swelling and nodule formation
• nodular enlargement -> joint deformity

2. Respiratory Manifestations

• hoarseness
• breathing difficulties +/- respiratory distress
• recurrent pneumonias

3. Gastrointestinal Manifestations

• feeding and swallowing difficulties
• failure to thrive
• hepatomegaly/hepatosplenomegaly in 25% of cases

4. Ocular Manifestations

• retina - cherry-red spot and pigmentary mottling
• granulomas in and around the eye

5. Neurological Manifestations

1. Diagnosis

• deficiency of ceramidase activity in lymphocytes or cultured skin fibroblasts
• prenatal
  • deficiency of ceramidase activity in cultured chorionic villi or amniocytes
• the identification of Farber Bodies on biopsy of nodules

2. Urine

• high levels of ceramide

3. Pathology

1. Supportive

• no treatment for underlying disease
• multidisciplinary approach
  • Paediatrics, Orthopedics, Ophthalmology, Gastroenterology,
  • Respirology
  • manage respiratory distress +/- upper airway obstruction
  • genetic counselling
• bone marrow transplantation is experimental

2. Prognosis

• severely affected - die before age 2 of pulmonary complications
• moderately affected - die between 5-10 years of age
• mildly affected - die in adulthood