Role of Ultrastructural Evaluation of Peripheral Blood in Diagnosis of Metabolic Storage Disorders
John Hicks, Eric Wartchow, Gary Mierau. Texas Children's Hospital & Baylor College of Medicine, Houston, TX; Children's Hospital of Colorado, Aurora, CO
Background: Lysosomal storage disorders in children are rare, occurring 1 in 1,500 to 7,000 births. These disorders are inherited deficiencies in 1 or more catabolic lysosomal enzymes. There are many steps necessary for synthesis and processing of lysosomal enzymes, making these processes prone to defects and dysfunction. Many different lysosomal storage disorders present in neonates, infants and young children with similar signs and symptoms.
Design: Surgical pathology and consultative archives of 2 pediatric hospitals were accessed over a 10 year period and identified 52 metabolic storage disorders that were diagnosed utilizing electron microscopy (EM) of peripheral blood mononuclear cells. Buffy coats comprised of peripheral mononuclear blood cells were prepared and examined by EM. The majority of the children were under 2 years of age (75%) with an age range from 1 month to 7 years.
Results: There were 3 categories of metabolic lysosomal disorders that were identified by characteristic storage material within peripheral blood mononuclear cells. Neuronal ceroid lipofuscinosis (Batten disease: mutations in CLN 1=>10 and CTSD genes) was most common(n=39/52) and the ultrastructural features allowed for characterization into infantile (granular osmophilic deposits), late infantile (curvilinear inclusions) and juvenile (fingerprint bodies) forms. Gaucher disease (β-glucocerebrosidase deficiency; n=9/52) was identified in the neonatal period (type 1) and early childhood (Type 3) with readily identified fine tubular helical/twisted structures distending the cytoplasm of mononuclear cells on ultrastructural examination. These tubular structures were seen in longitudinal and cross-sectional profiles and engorged the cytoplasm of peripheral blood mononuclear cells. Niemann-Pick disease (sphingomyelin-cholesterol lipidoses; sphingomyelinase deficiency) was identified in the remaining cases (n=4/52) in infants (Type A: infantile form). The inclusions in Niemann-Pick were characterized as pleomorphic lipid profiles that were generally membrane-bound whorled aggregates and multivesicular confluences with occasional lamellar material.
Conclusions: The current retrospective review demonstrates the utility of electron microscopy in evaluation of metabolic lysosomal storage disease in neonates, infants and children. Ultrastructural evaluation of peripheral blood mononuclear cells may provide for initial screening, preliminary diagnosis, and guide enzymatic and genetic testing.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 312, Wednesday Morning