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A case of combined Farber and Sandhoff disease
C Fusch1, R Huenges, H W Moser
1Universitäts-Kinderklinik, Rümelinstrasse Tübingen, Federal Republic of Germany.
Insights
This study details a rare case of combined Farber and Sandhoff disease in a 6-month-old girl, presenting unique lysosomal storage and enzyme deficiencies.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Farber disease is a rare lysosomal storage disorder caused by acid ceramidase deficiency.
- Sandhoff disease is a lysosomal storage disorder resulting from beta-hexosaminidase deficiency.
Observation:
- A 6-month-old girl presented with hoarseness, stridor, skin nodules, joint swelling, and cherry-red spots.
- Lysosomal inclusions typical of Farber disease and other inclusions like zebra bodies were observed in skin nodules.
- Clinical deterioration was noted in motor and physical condition, while mental state remained unchanged.
Findings:
- Biochemical analysis revealed ceramide accumulation and impaired degradation, consistent with Farber disease.
- Profoundly decreased beta-hexosaminidase activity and absent specific enzyme bands confirmed Sandhoff disease.
- Increased urinary oligosaccharides and partial enzyme deficiencies in the father suggested a combined genetic defect.
Implications:
- This case highlights the biochemical and clinical presentation of a rare combined lysosomal storage disorder.
- Further research is needed to understand the combined effects of these enzyme deficiencies and their genetic basis.
- The findings contribute to the understanding of complex genetic interactions in inherited metabolic diseases.
Abstract:
We describe a patient with the biochemically established combination of Farber and Sandhoff disease. A 6-month-old girl of consanguineous Turkish parents presented with hoarseness, stridor, scattered skin nodules, painful swelling of hand joints and ankles, and cherry-red macular spots. Until the age of 2 years her motor and physical condition deteriorated distinctly, however her mental state remained unchanged. A biopsied skin nodule disclosed lysosomal inclusions within storage cells that were typical of Farber disease (curved tubular structures). However, other inclusions (e.g. zebra bodies) were also found. Biochemical findings included ceramide accumulation in skin nodules and cultured fibroblasts, impaired ceramide degradation on loading of cultured fibroblasts with radioactive sphingomyelin, profoundly decreased ceramidase activity in fibroblasts as well as total beta-hexosaminidase activity in fibroblasts and serum, absent hexosaminidase A and B bands on cellogel zymograms, increased urinary oligosaccharide excretion of the Sandhoff disease type, and a partial reduction of ceramidase and total beta-hexosaminidase activities in fibroblasts from her father. A diagnosis of combined Farber and Sandhoff disease was made. The effect of both enzyme deficiencies on the clinical manifestations in this patient and the genetic basis of this combination require further studies.