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

Abstract

Ataxia-telangiectasia (AT) is a rare multisystem, neurodegenerative genetic disorder that is characterised by progressive neurological abnormalities, oculocutaneous telangiectasias and immunodeficiency. Delay in diagnosis or misdiagnosis is probable due to its wide clinical heterogeneity in infancy. Recurrent sinopulmonary infections are often the only presenting symptom and usually patients have decreased immunoglobulins. A total 10% of patients who present with decreased serum immunoglobulin G and A and with normal or elevated immunoglobulin M levels are often misdiagnosed as hyperimmunoglobulin M syndrome. Definitive diagnosis is made if a patient with progressive cerebellar ataxia has a disease causing mutation on the ATM gene. Ataxia-telangiectasia guideline of the European Society for Immunodeficiencies defines the probable diagnosis criteria. We evaluated twenty ataxia-telangiectasia patients (mean age 13.8±4.1 years) retrospectively who were followed-up for a mean of 38.6±27.0 months. Twelve patients had a family history of consanguinity. A total of 80% patients suffered from various infections. Neoplasms occurred in three of them. Patients showed immunological abnormalities as low IgG (45%), low IgA(65%) and elevated IgM (60%) levels. CD3+CD4+T lymphocyte frequency was low in 45% patients. The mean AFP concentration at the diagnosis was 191.9±140.1 ng/ mL and the raised IgM values did not show any statistically significant relationship with high AFP concentrations. Frequency of the elevated IgM concentrations in (60%) patients raises the concerns about thinking this finding has to be accepted as a probable diagnosis criterium.

Elevated IgM levels as a marker for a unique phenotype in patients with Ataxia telangiectasia

“…Hypogammaglobulinemia with low IgG, IgA and IgE levels, is a frequent presentation of this disease [ 27 ]. On the other hand, different studies have shown variability in IgM levels in these patients with normal or mildly elevated levels in up to 60% of the patients [ 19 ]. As a result, some AT patients are initially misdiagnosed with Hyper IgM syndrome, while the definitive AT diagnosis is made later by genetic analysis or western blot, following the accumulation of clinical characteristics indicative of AT.…”

“…Several reports have suggested that a subgroup of patients with AT present with higher levels of IgM that might be associated with a more severe phenotype [ 15 – 19 ]. A more recent study describing a cohort of 61 patients, concluded that patients with Hyper IgM phenotype and IgG2 deficiency showed decreased survival compared to AT patients with NIgM [ 20 ].…”

Ataxia Telangiectasia Diagnosed on Newborn Screening–Case Cohort of 5 Years' Experience

“…Diagnosis of AT patients may be delayed due to the wide variability in clinical phenotype; the syndrome is frequently confused with cerebral palsy and the immunological evaluation overlooked or misdiagnosed as Hyper-immunoglobulin M syndrome (9)(10)(11)(12).…”

An unusual manifestation: Papillary thyroid carcinoma in a patient with ataxia-telengiectasia

“…It is characterized by oculocutaneous telangiectasias, variable immunodeficiency and progressive neurological abnormalities such as uncoordinated, ataxic movements as a result of cerebellar cortical degeneration [1][2] . Other features include retardation of somatic growth, premature aging, radiosensitivity and predisposition to cancer 2 .…”

“…Other features include retardation of somatic growth, premature aging, radiosensitivity and predisposition to cancer 2 . Definitive diagnosis is made by revealing a disease causing mutation on ATM gene which was identified in 1995 in 11q22-23, coding for a protein implicated in genomic homeostasis in case of radio-induced DNA double-strand breaks [1][2][3] .…”