Hypoparathyroidism, retardation, and dysmorphism syndrome: impaired early growth and increased susceptibility to severe infections due to hyposplenism and impaired polymorphonuclear cell functions

Abstract

Hypoparathyroidism, retardation, and dysmorphism (HRD) syndrome is the first reported disease caused by a defect in the tubulin folding and assembly pathway. We aimed to summarize our experience with a cohort of patients with HRD, analyze their growth, and evaluate patients' polymorphonuclear cell (PMN) functions. The records of 22 HRD patients in a single medical center were reviewed. Growth during infancy and early childhood were analyzed by the Infancy-Childhood-Puberty (ICP) growth model. PMN functions were compared with healthy controls. Twelve patients died and many hospitalizations due to infections and convulsions were recorded. Growth measurements, expressed as weight and height SD scores in boys at a mean age of 4 y were -13.1+/-3.8 and -8.7+/-1 and -16.6+/-4.4 and -9.5+/-2.4, respectively, in girls at a mean age of 6.4 y. Chemotactic migration, random migration, and phagocytosis of PMN from HRD patients were significantly lower than that of PMN from healthy controls. No significant differences were found in superoxide production of PMN from patients compared with controls. Functional hyposplenism has been demonstrated in most of the studied patients. The defect in the tubulin folding and assembly pathway, previously described in HRD, has grave consequences on growth and PMN functions.