trypsinogen and Abnormalities--Multiple

To evaluate the role of serum enzymes for defining the pancreatic phenotype in Shwachman-Diamond syndrome (SDS), an inherited multisystem condition.. Serum pancreatic trypsinogen and isoamylase were measured in 164 patients known or presumed to have SDS. The diagnosis was confirmed in 90 patients. Among 74 unconfirmed cases, 35 ("probable SDS") had hematologic dysfunction but lacked documented pancreatic dysfunction, whereas 39 patients ("improbable SDS") lacked both documented pancreatic and hematologic dysfunction. Classification and regression tree (CART) analysis was performed in 90 patients with SDS and 134 control patients to establish a rule for defining the pancreatic phenotype of SDS; the rule was then applied to the patients with unconfirmed diagnosis.. In the control patients, serum trypsinogen showed little variation with age, whereas serum isoamylase values rose from birth on, attaining adult values by 3 years. For patients with SDS, serum trypsinogen values were low in young patients and tended to increase with age, whereas serum isoamylase values remained low at all ages. The CART rule combined results from both enzymes and classified the pancreatic phenotype in all but one SDS patient, who was <3 years of age. Excluding patients <3 years of age, CART identified the pancreatic phenotype in 82% and 7% of the "probable SDS" and "improbable SDS" cases, respectively.. Serum pancreatic enzymes are useful for determining the pancreatic phenotype and confirming the diagnosis of SDS.

Topics: Abnormalities, Multiple; Adolescent; Adult; Biomarkers; Child; Child Welfare; Child, Preschool; Chromosome Aberrations; Chromosomes, Human, Pair 7; Clinical Laboratory Techniques; Exocrine Pancreatic Insufficiency; Female; Hematologic Diseases; Humans; Infant; Infant Welfare; Intracranial Hemorrhages; Isoamylase; Male; Pancreas; Phenotype; Retrospective Studies; Syndrome; Trypsinogen

Shwachman-Diamond syndrome is a rare disorder of unknown cause. Reports have indicated the occurrence of affected siblings, but formal segregation analysis has not been performed. In families collected for genetic studies, the mean paternal age and mean difference in parental ages were found to be consistent with the general population. We determined estimates of segregation proportion in a cohort of 84 patients with complete sibship data under the assumption of complete ascertainment, using the Li and Mantel estimator, and of single ascertainment with the Davie modification. A third estimate was also computed with the expectation-maximization (EM) algorithm. All three estimates supported an autosomal recessive mode of inheritance, but complete ascertainment was found to be unlikely. Although there are no overt signs of disease in adult carriers (parents), the use of serum trypsinogen levels to indicate exocrine pancreatic dysfunction was evaluated as a potential measure for heterozygote expression. No consistent differences were found in levels between parents and a normal control population. Although genetic heterogeneity cannot be excluded, our results indicate that simulation and genetic analyses of Shwachman-Diamond syndrome should consider a recessive model of inheritance.

Topics: Abnormalities, Multiple; Adolescent; Adult; Algorithms; Child; Child, Preschool; Cohort Studies; Computer Simulation; Exocrine Pancreatic Insufficiency; Family Health; Female; Genes, Recessive; Genetic Heterogeneity; Hematologic Diseases; Heterozygote; Humans; Infant; Male; Models, Genetic; Paternal Age; Phenotype; Syndrome; Trypsinogen