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[A case of Sanfilippo syndrome type C: long-term clinical course and treatment]
J Tohyama1, Y Naganuma, S Shirane
1Department of Pediatrics, National Niigata Hospital, Kashiwazaki.
Insights
Sanfilippo syndrome type C, a rare genetic disorder, was observed in a Japanese girl with cognitive decline and physical symptoms. Enzymatic assays confirmed a deficiency in N-acetyltransferase activity, a key enzyme in heparan sulfate metabolism.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Sanfilippo syndrome is a rare lysosomal storage disease caused by defects in heparan sulfate degradation.
- Type C is characterized by a deficiency in the enzyme acetyl-CoA: a-glucosaminide N-acetyltransferase.
- Genetic disorders can manifest with diverse clinical presentations in affected individuals.
Observation:
- A Japanese girl presented with developmental delay, disorientation, sleep disturbances, and dysphagia at age 6 years 8 months.
- Physical examination revealed short stature, coarse facial features, joint contractures, and tonsillar hypertrophy, but no hepatomegaly or corneal clouding.
- Laboratory tests showed increased urinary glycosaminoglycans, predominantly heparan sulfate.
Findings:
- Enzymatic assays on skin fibroblasts confirmed a complete deficiency of acetyl-CoA: a-glucosaminide N-acetyltransferase activity.
- This deficiency directly implicates the N-acetyltransferase enzyme in the pathogenesis of Sanfilippo syndrome type C in this patient.
- Heparan sulfate accumulation was identified as the primary biochemical abnormality.
Implications:
- This case highlights the importance of early diagnosis and enzymatic testing for Sanfilippo syndrome type C.
- Understanding the specific enzyme deficiency aids in comprehending the disease's molecular mechanisms.
- The partial improvement of dysphagia with erythromycin suggests potential therapeutic avenues for managing specific symptoms.
Abstract:
We reported a Japanese girl with the Sanfilippo syndrome type C. She was born to healthy parents married consanguineously. She began to deteriorate and became disoriented at the age of 6 year and 8 month. She also developed sleep problems and dysphagia. Physical examination revealed short stature, slightly coarse facial features, contracture of the PIP joints and hypertrophy of the tonsils. There was neither hepatomegaly nor corneal clouding. Laboratory examination demonstrated an increase in urinary excretion of glycosaminoglycan. Electrophoresis of the urinary glycosaminoglycans indicated that heparan sulfate was the predominant component. Enzymatic assay using her skin fibroblasts demonstrated a complete deficiency of acetyl-CoA: a-glucosaminide N-acetyltransferase activity. Low dose erythromycin alleviated hypertrophy of her tonsils, thereby improving dysphagia.