Ataxia-telangiectasia patients presenting with hyper-IgM syndrome

Abstract

Ataxia-telangiectasia (A-T) is characterised by progressive neurological abnormalities, oculocutaneous telangiectasias and immunodeficiency (decreased serum IgG subclass and/or IgA levels and lymphopenia). However, 10% of A-T patients present with decreased serum IgG and IgA with normal or raised IgM levels. As cerebellar ataxia and oculocutaneous telangiectasias are not present at very young age, these patients are often erroneously diagnosed as hyper IgM syndrome (HIGM). Eight patients with A-T, showing serum Ig levels suggestive of HIGM on first presentation, are described. All had decreased numbers of T lymphocytes, unusual in HIGM. The diagnosis A-T was confirmed by raised alpha-fetoprotein levels in all patients. To prevent mistaking A-T patients for HIGM it is proposed to add DNA repair disorders as a possible cause of HIGM.

Fatal Outcome Despite Full Lympho-Hematopoietic Reconstitution After Allogeneic Stem Cell Transplantation in Atypical Ataxia Telangiectasia

“…In a cohort of 100 AT patients 9% present with a total IgG deficiency and normal or elevated IgM levels suggestive of a class-switch-recombination defect [4]. In consistence with other published cases [5][6][7], mildly elevated AFP values (22 months: 98 μg/l; reference 6-23 months: <87 μg/l, >23 months: <6,2 μg/l) and increased radiosensitivity (see Fig. 2), this child represents a case of Hyper IgM phenotype in an AT patient.…”

ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

“…This is a clear bias since the more severe patients are treated with i.v. Ig [28], as was also the case in the series by NOORDZIJ et al [13], which included A-T patients with hyper-IgM and severe immune deficiency. These findings suggest that the recognition of groups who may be at higher risk of lower pulmonary function may help to direct care and improve clinical outcomes in A-T.…”

“…The most common humoral immunological defects are markedly diminished or absent serum IgA and IgG 2 , and impaired antibody responses to vaccines [12]. Serum IgG level can be normal even when some IgG subclasses are reduced, although a subset of classical A-T patients (⩽10%) will have a severe early-onset hypogammaglobulinaemia [13] and increased IgM levels [14]. The A-T patients with increased serum IgM levels show a remarkably more severe disease course [12].…”

“…MCGRATH-MORROW et al [45] performed overnight polysomnography on 12 adolescents with A-T at a median (range) age of 16 (13)(14)(15)(16)(17)(18)(19)(20) years. All subjects in the study were wheelchair-bound and the median (range) FVC was 44 (16-82)% pred.…”

Do Elevated Serum IgM Levels Have to Be Included in Probable Diagnosis Criteria of Patients with Ataxia-Telangiectasia?

“…Recently, case reports presenting with an unexplained immunodeficiency syndrome with decreased immunoglobulin levels in the presence of B cells and high IgM concentrations (21)(22)(23) have been published in the literature. In our group, the raised initial IgM values in 60% patients were noteworthy although concentrations showed no statistically significant relationship with the presence of infection (p: 0.626) or IVIg therapy (p: 0.853).…”