Rambam–Hasharon syndrome of psychomotor retardation, short stature, defective neutrophil motility, and bombay phenotype

Abstract

We describe 2 Arab patients, both offspring of unrelated consanguineous matings, with unusual facial appearance, severe mental retardation, microcephaly, cortical atrophy, seizures, hypotonia, dwarfism, and recurrent infections with neutrophilia. Neutrophil motility was markedly decreased but the opsonophagocytic activity was normal. Both patients lack the red blood cell (RBC) H antigen and manifest the Bombay (hh) phenotype. Familial endocardial fibroelastosis and familial tetralogy of Fallot segregated independently in one family. The occurrence of the same syndrome in 2 unrelated families suggests that the various aspects of the disorder are the pleiotropic effects of a single mutation. Homozygosity-by-descent for a deletion involving contiguous genes may explain the findings in this syndrome. Alternatively, a mutation which involves an ubiquitous GDP fucose donor rather than the enzyme (alpha 2-L-fucosyltransferase) or its substrate (glcNAc) may account for the pleiotropic manifestations in this syndrome.

Mechanisms in Protein O-Glycan Biosynthesis and Clinical and Molecular Aspects of Protein O-Glycan Biosynthesis Defects: A Review

“…Cell binding to E-and P-selectin is severely impaired (196 ). Mutations in FUCT lead to a lack of Fuc residues in N-and mucin-type O-glycans, whereas the biosynthesis of O-fucosyl glycans is normal (197 ).…”

Decreased availability of GDP-l-fucose in a patient with LAD II with normal GDP-d-mannose dehydratase and FX protein activities

“…Leukocyte adhesion deficiency type II (LAD II) was first described in two Arab boys aged 2.5 and 4.5 years by [1,2]. Until recently, no other patients have been identified.…”

Impairment of the Golgi GDP-l-Fucose Transport and Unresponsiveness to Fucose Replacement Therapy in LAD II Patients

“…LAD II (OMIM 266265) is a rare autosomal recessive syndrome initially described in Arab children in Israel (1)(2)(3)(4)(5). The disease is characterized by a set of clinical symptoms that include severe growth and mental retardation, unusual facial appearance, dwarfism, neurologic abnormalities, immunodeficiency with recurrent bacterial infections, leukocytosis (with white blood cell counts ranging from 25,000 to 150,000/mm 3 ), and Bombay blood phenotype (1,2).…”

“…The disease is characterized by a set of clinical symptoms that include severe growth and mental retardation, unusual facial appearance, dwarfism, neurologic abnormalities, immunodeficiency with recurrent bacterial infections, leukocytosis (with white blood cell counts ranging from 25,000 to 150,000/mm 3 ), and Bombay blood phenotype (1,2). The biochemical hallmark is a lack of expression of fucosylated glycoconjugates, including H-antigen and Lewis antigens such as Lewis X (LeX) and sialyl-Lewis X (SLeX) (1).…”