Farber disease: A clinical diagnosis.

Dear Sir,

A 10-month-old boy was referred to our department for hoarseness and joint contractures. His birth weight was 2,760 g. His parents realized hoarseness and limb contractures when he was 2 months old. Subcutaneous nodules were realized when he was 4 months old. He was the second child of non-consanguineous parents. There was no family history of a similar disease.

He was referred to our department when he was 10 month old. He weighed 4,880 g and was 67 cm length with a head circumference of 40.5 cm. He was interactive. But he had head lag and axial hypotonia, fish mouth, joint contractures and subcutaneous nodules located on fingers, back and knee [Figures 1 and 2]. His vital parameters and general physical examination were within normal limits. Ophthalmologic examination was normal. Blood cell count, erythrocyte sedimentation rate, C-reactive protein, biochemical parameters, cranial magnetic resonance imaging (MRI), and abdominal ultrasound were all normal. Extensive metabolic screening was negative. Biopsy of the nodular swelling revealed highly cellular tissue with scattered large foamy cells in deep dermis and fibrosis. Ceramidase level estimation and genetic studies could not be done. Typical clinical presentation and histopathologic findings in the above case clinched the diagnosis of Farber's disease.

Figure 1

Subcutaneous nodules at interphalangeal articulations

Figure 2

Subcutaneous nodules at spine

Farber's disease is a lysosomal storage disease which was first described by Farber (1957).[1] It is an autosomal recessive disorder caused by lysosomal acid ceramidase deficiency.[2] Acid ceramidase is an enzyme that in humans is encoded by the ASAH1 gene.[34] Normally, the enzyme ceramidase breaks down fatty material in the body's cells. In Farber's Disease, the gene responsible for making this enzyme is mutated.

Disease onset is typically in early infancy but may occur later in life. Children who have the classic form of Farber's disease develop symptoms within the first few weeks of life. It is characterized by a clinical triad including painful joint deformity, subcutaneous nodules, and hoarseness. Subcutaneous nodules appear especially near the joints and on pressure points. Rarely, these nodules are reported in other sites including the conjunctivae, nostrils, ears, and oral cavity.[2] The liver, heart, and kidneys may also be affected. Macular cherry-red spots are described in the most reported cases. But ophthalmologic examination was normal in our case. Most infants have problems about feeding and respiratory system. The central nervous system is variably affected, leading to a severe progressive impairment of psychomotor development and neurologic deterioration with epilepsy.[2] Children with significant neurological involvement usually die early in infancy, whereas patients without or only mild neurological findings suffer from progressive joint deformation and contractures, subcutaneous nodules, inflammatory, periarticular granulomas, a hoarse voice, and finally respiratory insufficiency caused by granuloma formation in the respiratory tract and interstitial pneumonitis leading to death in the third or fourth decade of the life.[5]

Ceramidase level estimation and genetic studies can be done for diagnosis. But we diagnosed Farber's disease with typical clinical presentation and histopathologic findings in our case.