Farber Uzman Syndrome

At a glance

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 in early age can reach adulthood). Severe motor and mental retardation is evident.

Synonyms

Acid Ceramidase Deficiency; Farber Lipogranulomatosis; Farber Disease.

Incidence

Approximately 50 cases have been reported in the literature. Equally represented in males and females.

Genetic inheritance

Autosomal recessive.

Pathophysiology

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 central nervous system [CNS]).

Diagnosis

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 amniocytes).

Clinical aspects

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.

Precautions before anesthesia

If bone marrow involvement is suspected, a complete blood cell count (CBC) is recommended. An ECG and echocardiogram are recommended if valvular involvement caused by the disease is suspected.

Anesthetic considerations

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.

Pharmacological implications

Increased level of unbound drug because of decreased albumin level. Lower threshold for local anesthetic toxicity is reported. Use of succinylcholine is not recommended if there is a severe denervation myopathy and the overall need for muscular relaxant will be minimal.

Other condition to be ...