Inborn error of the fatty metabolism caused by a
lysosomal enzyme deficiency and resulting in the accumulation of ceramide in
body tissues with multiple organ failure and death in infancy (but mildly
affected patients can reach adulthood). Severe motor and mental retardation
Acid Ceramidase Deficiency; Farber Lipogranulomatosis;
Approximately 50 cases have been reported in the
literature. Equally represented in males and females.
Accumulation of ceramide in tissue as a result of
a deficiency of lysosomal acid ceramidase. This accumulation causes cell
damage with an inflammatory response resulting in the formation of nodules
or granules (not involving the CNS).
Suspected based on the classic triad of symptoms:
synovial thickening associated with joint stiffness, subcutaneous
granulomas, and hoarseness as a consequence of laryngeal involvement. It is
established by the deficiency of ceramidase activity in lymphocytes or
cultured skin fibroblasts and the identification of Farber bodies on biopsy
of nodules (characteristic inclusions). Prenatal diagnosis is available
(deficiency of ceramidase activity in cultured chorionic villi or
Characterized by progressive hoarseness, noisy
respiration, nutritional failure associated with poor growth and
development, multiple subcutaneous and periarticular nodules, and
progressive arthropathies. Accumulation of ceramide in the nervous system
causes psychomotor retardation, peripheral neuropathy, and muscle
denervation. The heart can be involved in the disease process, with the
presence of granulomas on cardiac valves. This clinical picture mainly fits
the classic type I disease. Some other subtypes, which are even more
unusual, may present with ocular, neurologic, and bone marrow involvement.
If bone marrow involvement is
suspected, a CBC is recommended. An ECG and echocardiogram are recommended
if valvular involvement caused by the disease is suspected.
Because of the presence of granulomas in
the oral cavity, direct laryngoscopy and tracheal intubation may be difficult as a consequence of
diminished space and poor visualization. Also, nutritional failure decreases
albumin level and so increases the unbound fraction of many drugs. Cardiac
disease, if present, should be managed appropriately. Antibioprophylaxis may
be required. Finally, joint contractures require proper positioning of the
patient on the operating room table.
Increased level of unbound drug
because of decreased albumin level. Lower threshold for local anesthetic
toxicity. Use of succinylcholine is not recommended if there is a severe
denervation myopathy and the overall need for muscular relaxant will be
Erdheim-Chester Disease (ECD): Rare histiocytic disorder characterized
by non-Langerhans cell histiocytosis resulting in extensive lipoid
granulomas in various parts of the body and organs. Clinical manifestations
range from asymptomatic to fatal multisystem involvement, typically bones,
kidneys, hearts, and lungs.
Bar J, Linke T, Ferlinz K, et al: Molecular analysis of acid ceramidase
deficiency in patients with Farber disease. Hum Mutat
Haraoka G, Muraoka M, Yoshioka N, et al: First case of surgical ...