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Aqneursa (levacetylleucine)

Ataxia-telangiectasia

Also known as IB1001
Manufacturer
IntraBio
Last updated
206 sources

Product information and disease descriptionPlace of product in therapyDisease description

Clinical presentation - signs and symptoms

16 evidence topics · 21 sources

Presenting symptoms

“1314 cases reported 2134 presenting symptoms. The most common presenting symptom was abnormal gait (1160 cases; 188 studies) followed by recurrent infections in classical ataxia-telangiectasia and movement disorders in variant ataxia-telangiectasia.” (opens the source at this quote in a new tab)

“As expected, cerebellar gait ataxia was the most reported first presenting symptom however over a quarter did not have ataxia as their first clinical presentation. Dysarthria was reported as the first presentation in 9% of cases.” (opens the source at this quote in a new tab)

“Initial manifestations of Ataxia-telangiectasia include cerebellar symptoms (67%), dystonia (18%), choreoathetosis (10%), and tremor (4%), with parkinsonism and myoclonus not reported as initial features.” (opens the source at this quote in a new tab)

Motor symptoms: cerebellar ataxia of gait, trunk, and limbs

“In most children with classic A-T, cerebellar ataxia is the presenting manifestation observed after the child starts to sit and walk” (opens the source at this quote in a new tab)

“Infants show postural instability when sitting or standing. Although children start to walk at a normal age, their gait does not improve and remains wobbly.” (opens the source at this quote in a new tab)

“Ataxia may be comprised of multiple signs and symptoms, including gait ataxia, truncal ataxia, oculomotor ataxia, and difficulties with balance, speech, and hand coordination.” (opens the prescribing information at this quote)

“Generally children learn to walk at the usual age (about 10-18 months of age), but remain a bit unsteady, like normal children who have only just learned to walk, then become more wobbly (ataxic) over 2-3 years with frequent falls, then actually cannot get about as well as they used to from 5-6 years.” (opens the source at this quote in a new tab)

Neurological signs in a British Isles cohort of 70 individuals

“The majority (43/68) presented by 3 years of age with truncal ataxia. All had progressive, handicapping neurological symptoms exhibiting ataxia (70/70), ocular motor apraxia (70/70), an impassive face (70/70), dysarthria (70/70), chorea (68/70), dystonia (55/70) and peripheral neuropathy (50/70).” (opens the source at this quote in a new tab)

“Clinical immune deficiency was present in 43 of 70 patients. Ocular telangiectasia were seen in all but one case and excessive thinness in 54 of 70.” (opens the source at this quote in a new tab)

Motor symptoms: extrapyramidal movement disorders

“The prevalence of movement disorders during the course of the disease includes cerebellar symptoms (96%), dystonia (89%), parkinsonism (41%), choreoathetosis (89%), myoclonus (92%), and tremor (74%).” (opens the source at this quote in a new tab)

“In addition, most children with classic A-T have extrapyramidal involvement such as dystonia, choreoathetosis, myoclonic jerks, and tremor. In the second or third decade, parkinsonism can occur” (opens the source at this quote in a new tab)

“Dystonia was present in 11/14 (79%) and chorea was present in 6/14 (43%).” (opens the source at this quote in a new tab)

Peripheral nervous system symptoms: sensorimotor neuropathy

“After about age eight years children begin to show clinical signs of peripheral neuropathy, manifesting as a progressive sensorimotor neuropathy, decreased or loss of deep tendon reflexes, distal muscle weakness and atrophy, and impaired vibration sense” (opens the source at this quote in a new tab)

“In this prospective study, 42 classical A-T patients were assessed.” (opens the source at this quote in a new tab)

“We found significant correlations between age and the development of motor and sensory polyneuropathy in A-T compared with healthy controls (p < 0.001).” (opens the source at this quote in a new tab)

Oculomotor symptoms: oculomotor apraxia, saccade abnormalities, and nystagmus

“Abnormal eye movements associated with A-T include: oculomotor apraxia, nystagmus (including horizontal nystagmus in primary gaze, nystagmus on lateral gaze, post-rotary nystagmus and periodic alternating nystagmus), hypometric saccades and saccadic intrusions, convergence/accommodation and VOR abnormalities” (opens the source at this quote in a new tab)

“Visual acuity was preserved in most patients, with 24 (79%) achieving 6/12 or better.” (opens the source at this quote in a new tab)

“Eye movement recordings revealed hypometric saccades, increased latency, impaired smooth pursuit (especially vertical) and frequent nystagmus.” (opens the source at this quote in a new tab)

Bulbar symptoms: dysarthria

“With disease progression, speech problems occur in all individuals. Despite dysarthria, oral communication generally remains possible” (opens the source at this quote in a new tab)

“Early language development is normal, but by school entry most children with typical A-T will have a quiet voice, with indistinct words, which gradually become harder for strangers to understand.” (opens the source at this quote in a new tab)

Bulbar symptoms: dysphagia and aspiration

“Seventy patients (mean age, 10.7 years; range, 1.8 to 30 years) had feeding/swallowing and nutritional evaluations.” (opens the source at this quote in a new tab)

“Fourteen of the 51 patients (27%) with histories suggestive of dysphagia demonstrated aspiration. Of these, silent aspiration (aspiration without a cough) occurred in 10 (71%) patients.” (opens the source at this quote in a new tab)

“Aspirators were significantly older than non-aspirators (mean age, 16.9 vs 10.8 years; P =.002).” (opens the source at this quote in a new tab)

“Dysphagia is common in A-T and typically appears during the second decade of life because of the neurological changes which interfere with the coordination of mouth and pharynx movements necessary for safe and efficient swallowing” (opens the source at this quote in a new tab)

Ocular and cutaneous signs: telangiectasia

“Telangiectasia within the bulbar conjunctiva over the exposed sclera of the eyes usually occur by the age of 5–8 years, but sometimes later or not at all” (opens the source at this quote in a new tab)

“The absence of telangiectasia does not exclude the diagnosis of A-T.” (opens the source at this quote in a new tab)

“Strabismus was identified in four (13%) and moderate to severe conjunctival telangiectasia was present in 20 (67%) patients.” (opens the source at this quote in a new tab)

Immunological symptoms: immunodeficiency and infections

“Immunoglobulin (Ig) deficiencies are common, affecting IgG4 in 65% of patients, IgA in 63%, IgG2 in 48%, IgE in 23%, and IgG in 18%. Lymphopenia affected 71% of patients, with reduced B-lymphocyte number in 75%, CD4 T lymphocytes in 69%, and CD8 T lymphocytes in 51%.” (opens the source at this quote in a new tab)

“Recurrent upper and lower respiratory tract infections were frequent: otitis media in 46% of patients, sinusitis in 27%, bronchitis in 19%, and pneumonia in 15%.” (opens the source at this quote in a new tab)

“In spite of the high prevalence of laboratory immunologic abnormalities, systemic bacterial, severe viral, and opportunistic infections are uncommon in A-T.” (opens the source at this quote in a new tab)

“IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%.” (opens the source at this quote in a new tab)

“Infections were reported in the majority of the cohort (88%; 61/69).” (opens the source at this quote in a new tab)

“In this study we analyse the clinical history and immunological data in 44 patients with A-T who attended the National Ataxia-Telangiectasia clinic in Nottingham between 2001 and 2011.” (opens the source at this quote in a new tab)

“However, in general, for the majority of patients the severity of immune deficiency (both clinically and in terms of immunological blood markers) does not seem to deteriorate significantly with time.” (opens the source at this quote in a new tab)

Respiratory symptoms: lung disease phenotypes

“There are three recognised major lung disease phenotypes. 1) Immune dysfunction leading to recurrent upper and lower respiratory tract infections (RTIs), which in turn can lead to bronchiectasis; 2) lung disease associated with dysfunctional swallow and inefficient cough due to neurodegenerative deficits, which increases the risk for aspiration and consequently may also cause or worsen bronchiectasis; and 3) ILD/pulmonary fibrosis.” (opens the source at this quote in a new tab)

“Lingering cough, chest congestion and/or wheeze may be early symptoms of underlying lung disease in a person with A-T.” (opens the source at this quote in a new tab)

“Patients with A-T showed significant differences compared to healthy controls in symptom score, daytime and nighttime cough, days with symptoms and missed days in kindergarten/school. Severe infections with hospitalization occurred rarely.” (opens the source at this quote in a new tab)

Malignancy: tumor types in children and adults

“Children are prone to developing lymphomas (B-cell non-Hodgkin lymphoma and Hodgkin lymphoma) and leukemias (most notably T-cell acute lymphoblastic leukemias and T-cell prolymphocytic leukemia)” (opens the source at this quote in a new tab)

“In addition to hematologic malignancies, adults are prone to developing solid tumors including breast cancer, ovarian cancer, gastric cancer, liver cancer, esophageal carcinomas, melanomas, leiomyomas, and sarcomas” (opens the source at this quote in a new tab)

Endocrine and growth abnormalities

“We found that classic A-T patients were smaller overall, and suffered from height and weight faltering that continued throughout childhood and adolescence. When compared to the CDC growth references, the median heights and weights for both male and female patients eventually fell to or below the 3rd centile on the CDC charts.” (opens the source at this quote in a new tab)

“Endocrine abnormalities include growth impairment, gonadal dysfunction, and insulin resistance” (opens the source at this quote in a new tab)

“Elevated LH and FSH levels are common in adolescent females with A-T, indicating ovarian failure.” (opens the source at this quote in a new tab)

“Short stature, here defined as more than 2 standard deviations below age-adjusted average height at latest assessment, was present in 6/13 (46%) patients” (opens the source at this quote in a new tab)

Cognitive symptoms

“Cognitive deficits in AT at a young age are mild and limited to visual-spatial functions. More widespread cognitive difficulties emerge with age and disease progression, impacting executive function, spatial skills, affect, and social cognition.” (opens the source at this quote in a new tab)

“Although it is generally accepted that intellectual disability is not common in A-T, disturbances in cerebellar as well as non-cerebellar brain areas and networks may result in cognitive deficits.” (opens the source at this quote in a new tab)

Radiosensitivity

“People with A-T have an increased sensitivity to ionizing radiation (X-rays and gamma rays), which can be cytotoxic. X-ray exposure should be limited to times when it is medically necessary for diagnostic purposes.” (opens the source at this quote in a new tab)

“Increased sensitivity to ionizing radiation (x-ray and gamma ray) can result in severe side effects from such treatments.” (opens the source at this quote in a new tab)

Presentation of variant A-T

“Only one third had predominant ataxia, and 18% had a pure extrapyramidal presentation.” (opens the source at this quote in a new tab)

“There were no significant respiratory or immunological complications, but 25% of individuals had a history of malignancy.” (opens the source at this quote in a new tab)

“They often presented with extrapyramidal symptoms in childhood, whereas cerebellar ataxia appeared later.” (opens the source at this quote in a new tab)

“Variant A-T has a significantly milder disease course. While cerebellar ataxia can be absent, extrapyramidal movement disorders are common (typically dystonia and dystonic tremor) and most individuals have manifestations of axonal sensorimotor polyneuropathy.” (opens the source at this quote in a new tab)