A rare defect of fucose metabolism leading to a
syndrome that combines neutrophil adhesion deficiency with severe
neurological impairment, psychomotor retardation and short stature.
Leukocyte Adhesion Deficiency type II; Congenital
Disorder of Glycosylation type IIc.
First described in 1992 in two unrelated boys, both
offspring of consanguineous parents in Israel.
Inborn deficiency of several fucosylated
glycoproteins. Caused by mutation in the gene encoding guanosine diphosphate
(GDP)-fucose transporter-1 (FUCT1) located on chromosome 11. Lack of CD15, a
cell-surface glycoprotein, leads to marked decrease in neutrophil motility.
Lack of H antigen, a precursor to ABO antigen, leads to Bombay blood type
Clinically evocated in patients with unusual facial
appearance, severe mental retardation, microcephaly, cortical atrophy,
seizures, hypotonia, dwarfism, and recurrent infections with neutrophilia.
Blood typing, leukocyte function test, and chromosomal study will confirm
diagnosis. Can be diagnosed prenatally with cordocentesis for blood typing
in suspected fetus.
Five cardinal manifestations can be defined: (a)
Unusual facial appearance: microcephaly, coarse features, flat face, hypertelorism, anteverted
nostrils, long upper lip, large protruding tongue, narrow palate, mandible
may be small and retracted. (b) central nervous system: severe mental retardation, seizure,
hypotonia, cerebral cortical atrophy. (c) Short stature: dwarfism. (d) Defective neutrophil motility: recurrent
bacterial infection with neutrophilia common, particularly pneumonia,
periodontitis, otitis media, and localized cellulitis with pus formation.
(e) Bombay blood phenotype.
Absence of pus formation at site of infection is common. Frequency of
infections decreases generally after age of 3 years.
Assess for evidence of concurrent
infection, particularly pneumonia. Assess neurological function, including
seizure control (clinical, EEG, CT). Assess airway for possible difficult
tracheal intubation (clinical, radiographs). Ensure availability of blood if
transfusion is anticipated.
Strict asepsis is needed because of
neutrophil function alteration. No known particular risk with anesthesia. In
view of the abnormal facies, should prepare for airway difficulties if they
appear likely in the preoperative assessment. Careful intraoperative
positioning is needed.
Consider interaction between
antiepileptic treatment and anesthetic drugs. Muscle relaxants should be
avoided until airway is secured. Consider prophylactic antibiotics as in
Etzioni A, Sturla L, Antonellis A, et al: Leukocyte adhesion deficiency
(LAD) type II/carbohydrate deficient glycoprotein (CDG) IIc founder effect
and genotype/phenotype correlation. Am J Med Genet
Frydman M, Etzioni A, Eidlitz-Markus T, et al: Ramban-Hasharon syndrome of
psychomotor retardation, short stature, defective neutrophil motility and
Bombay phenotype. Am J Med Genet
Hidalgo A, Ma S, Peired AJ, et al: Insights into leukocyte adhesion
deficiency type 2 from a novel mutation in the GDP-fucose transporter gene.
Blood 101(5):1705, 2003.