Free Sialic Acid Storage Disease Mimicking Cerebral Palsy and Revealed by Blood Smear Examination
Article Outline
Cerebral palsy caused by perinatal insult is a frequent cause of static encephalopathy, but metabolic or genetic disorders can present with similar nonspecific features. A 6-year-old boy was evaluated for severe encephalopathy. His medical history revealed neonatal asphyxia due to accidental birth outside the hospital and neonatal infection. A sister had died at age 4 years with similar neurologic features. Clinical examination revealed spastic tetraparesis, failure to thrive, microcephaly (-3 SD), and absence of psychomotor development. Hepatosplenomegaly was not present. Cerebral magnetic resonance imaging (MRI) showed cerebral and cerebellar atrophy, corpus callosum hypoplasia, diffuse white matter hyperintensities, and subdural hematoma. Skeletal radiography showed bilateral hip luxation with no sign of multiplex dysostosis. Blood smear examination revealed the presence of vacuolation in a large percentage (>60%) of lymphocytes and abnormal granulation in eosinophils (Figure). Urinary glycosaminoglycan and oligosaccharide levels were normal, but free sialic acid level was markedly elevated (5481 μmol/g of creatinine [normal, 100-380]). A younger brother, age 6 months, presented with psychomotor delay without organomegaly but with increased urinary sialic acid excretion. Molecular analysis revealed homozygosity for the G140R mutation in the SLC17A5 gene.
Figure.
A and B, The patient and his younger brother. C and D, Blood smears showing vacuolated lymphocytes and abnormal granulations in eosinophils. E and F, Cerebral MRIs showing cerebral atrophy, diffuse abnormalities of the white matter, and subdural hematoma.
Sialic storage diseases (SSDs) include infantile SSD, characterized by severe progressive encephalopathy, visceral storage, and early mortality, and, at the mildest end of the clinical spectrum, Salla disease, characterized by slowly progressive course, mental retardation, and normal life span.1 Our two patients represent an intermediate phenotype.2
Neurometabolic diseases should be considered in infants presenting with unexplained encephalopathy. Lysosomal storage diseases can mimic cerebral palsy, occurring in the absence of visceral involvement. Examination of blood smear is necessary; vacuolated lymphocytes are an important clue pointing to lysosomal disorders, even in the absence of hepatosplenomegaly. Because sialidase activity is normal, oligosaccharide electrophoresis is normal; thus, diagnosis cannot be based on lysosomal screening tests, but requires specific sialic acid measurement.
References
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- . Novel form of intermediate Salla disease: clinical and neuroimaging features. J Child Neurol. 2005;20:814–816
PII: S0022-3476(10)00571-8
doi:10.1016/j.jpeds.2010.06.057
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