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Ataxia Telangiectasia: a Diagnostic Challenge. Case Report

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Ataxia Telangiectasia: a Diagnostic Challenge. Case Report case reports 2020; 6(2) https://doi.org/10.15446/cr.v6n2.83219 ATAXIA TELANGIECTASIA: A DIAGNOSTIC CHALLENGE. CASE REPORT Keywords: Ataxia Telangiectasia; Neurodegenerative Diseases; Cerebellar Ataxia; Spinocerebellar Degenerations; Telangiectasia. Palabras clave: Ataxia telangiectasia; Enfermedades neurodegenerativas; Ataxia cerebelosa; Degeneraciones espinocerebelosa; Telangiectasia. Natalia Martínez-Córdoba Universidad Militar Nueva Granada - Faculty of Medicine - Pediatric Neurology Research Group - Bogotá D.C. - Colombia. Hospital Militar Central - Pediatric Neurology Service - Bogotá D.C. - Colombia. Eugenia Espinosa-García Universidad Militar Nueva Granada - Faculty of Medicine - Pediatric Neurology Research Group - Bogotá D.C. - Colombia. Hospital Militar Central - Pediatric Neurology Service - Bogotá D.C. - Colombia. Universidad del Rosario - Medical School - Bogotá D.C. - Colombia. Corresponding author Natalia Martínez-Córdoba. Faculty of Medicine, Universidad Militar Nueva Granada. Bogotá D.C. Colombia. Email: [email protected]. Received: 28/10/2019 Accepted: 08/01/2020 case reports Vol. 6 No. 2: 109-17 110 RESUMEN ABSTRACT Introducción. La ataxia-telangiectasia (AT) es Introduction: Ataxia-telangiectasia (AT) is a un síndrome neurodegenerativo con baja inciden- neurodegenerative syndrome with low incidence cia y prevalencia mundial que es causado por una and prevalence worldwide, which is caused by a mutación del gen ATM, es de herencia autosó- mutation of the ATM gene. It is an autosomal re- mica recesiva y se asocia a mecanismos defec- cessive disorder that is associated with defective tuosos en la regeneración y reparación del ADN. cell regeneration and DNA repair mechanisms. It Este síndrome se caracteriza por la presencia de is characterized by progressive cerebellar atax- ataxia cerebelosa progresiva, movimientos ocula- ia, abnormal eye movements, oculocutaneous res anormales, telangiectasias oculocutáneas e telangiectasias and immunodeficiency. Early inmunodeficiencia. El diagnóstico oportuno de la diagnosis is critical to initiate a timely interdis- AT es muy importante para poder iniciar un manejo ciplinary treatment, improve acute symptoms, interdisciplinario temprano, mejorar la sintomato- and control the multiple comorbidities of the logía aguda y controlar las múltiples comorbilida- disease. The following is the case of a patient des que causa. A continuación se presenta el caso who presented with the aforementioned char- de una paciente con las características clásicas acteristics and had an adequate response to de esta enfermedad y una adecuada respuesta the established medical treatment. y evolución al manejo médico instaurado. Case presentation: A 7-year-old female pa- Presentación de caso. Paciente femenina de tient from Bogotá, who presented clinical signs 7 años de edad, procedente de Bogotá, quien of global neurodevelopmental delay, cerebellar presentó cuadro clínico inicial de retraso global ataxia, frequent respiratory infections and ocu- del neurodesarrollo, ataxia cerebelosa, infec- lar telangiectasias. Symptoms were associated ciones respiratorias frecuentes y telangiectasias with elevation of alpha fetoprotein and immu- oculares. La sintomatología se asoció a elevación nodeficiency, which allowed for a diagnosis of de alfa fetoproteína e inmunodeficiencia, lo que AT and the initiation of a timely interdisciplinary permitió plantear el diagnóstico de AT e iniciar treatment. de manera oportuna el manejo interdisciplinario. Conclusion: AT is a chromosomal instability Conclusión. La AT es un síndrome de inestabili- syndrome with characteristic signs and symp- dad cromosómica con signos clínicos y síntomas toms. It is essential to know the etiopathogene- característicos, por lo que es primordial conocer la sis, clinical manifestations, diagnostic criteria, etiopatogenia, el cuadro clínico, los criterios diag- and therapeutic options, emphasizing that ear- nósticos y las propuestas terapéuticas, pues la ly detection and clinical suspicion could favor detección y la sospecha clínica temprana pueden the proper management of the comorbidities favorecer el manejo precoz de las diferentes co- and improve the progressive course of the morbilidades y mejorar el curso progresivo. disease. ataxia telangiectasia: a diagnostic challenge INTRODUCTION CASE PRESENTATION 111 Ataxia-telangiectasia (AT), also known as Bod- Mestizo, female patient, 7 years old, from Bogotá er-Sedgwick syndrome or Louis-Bar syndrome, D.C., Colombia, and the product of a second is a multisystemic, neurodegenerative, autoso- pregnancy by young, non-blood related, mid- mal recessive disease associated with the ATM dle-class parents. The girl had no significant pre- gene mutation (A-T-mutated), which is located natal history and was born by cesarean section at on the long arm of chromosome 11 (11q22-23). 35 weeks of gestation. Her weight at birth was (1) This syndrome affects multiple organs of the 1 800gr and her size was 40cm; the APGAR body and has moderate and severe long-term score was 4/10, 7/10 and 7/10 at 1 minute, sequelae. 5 minutes and 10 minutes, respectively. She AT is characterized by progressive neu- also presented with neonatal hypoxia, requiring rological dysfunction with multisystemic mechanical ventilation for 24 hours and hospi- alterations and predisposition to cancer. The talization in the neonatal intensive care unit for characteristic symptoms of this disease usually 20 days. appear early in childhood and include cere- The child’s psychomotor development was bellar ataxia, oculomotor apraxia, chorea, and normal until the age of 20 months, at which cognitive impairment. (2) Moreover, the cells time it was evident that there was language of AT patients present chromosomal instability, delay, café-au-lait spots and unsteady gait. At hypersensitivity to X-rays, propensity to lym- 31 months, she was referred to the Neuropedi- phoid neoplasms, variable immunodeficiency, atrics Service, which requested magnification and susceptibility to infections, which cause and brain magnetic resonance imaging (MRI) systemic symptoms such as endocrinopathies, studies; management with physical and lan- leukemias, radiosensitivity and ocular telangi- guage therapy was initiated. ectasias. (3,4) At 5 years of age, the patient was taken to While over 400 mutations of the ATM gene the emergency department due to a possible have been detected, it has been reported that focal onset impaired awareness seizure. During AT has an incidence of 1 between 40 000 and the interview, psychomotor and language delays 100 000 people (5) and that its frequency of were observed, as well as multiple respirato- heterozygosity in the mutant allele is 1.4% to ry and gastrointestinal tract infections. The 2% in the general population. (1,3) neurological examination revealed bradylalia, This disease is usually diagnosed late, as it bradypsychia, ataxic gait with enlargement of is only identifiable when patients have severe the support polygon, presence of oculomotor symptoms that begin with alterations in the apraxia, dysmetria and telangiectasias in sclera motor system. In addition, it is often misdiag- (Figure 1), so more specific tests were requested. nosed as cerebral palsy. (6) Finally, since MRI showed cerebellar atrophy So far there is no specific treatment for AT, (Figure 2), video-electroencephalography so its management is palliative and supportive. (EGG) was normal, alpha-fetoprotein (AFP) (7) Patients with this disease should participate levels were elevated, and immunological tests in daily and social integration activities, always were altered (Table 1), a diagnosis of AT was trying to maintain their quality of life. suggested. case reports Vol. 6 No. 2: 109-17 112 Figure 1. Patient with sclera telangiectasia. Source: Document obtained during the study. Figure 2. Brain MRI showing cerebellar vermian atrophy. A) Sagittal plane / T1 sequence; B) Coronal plane / FLAIR sequence. Source: Document obtained during the study. Table 1. Laboratory tests performed during patient follow-up. First sample Second sample Third sample Reference Test (11/09/2017) (09/05/2018) (04/06/2019) values IgA mg/dL 94 77.3 76.9 58-311 IgM mg/dL 157 147 174.5 84-383 IgG1 mg/dL 6.34 6.34 7.97 3.06-9.450 IgG2 mg/dL 0.56 2.34 3.05 0.605-3.450 IgG3 mg/dL 0.57 0.44 0.41 0.099-1.221 IgG4 mg/dL 0.01 0.10 0.15 0.018-1.125 CD3 669 672 778 1400-3700 CD4 282 265 256 700-2200 CD8 639 301 443 490-1300 Alpha- Fetoprotein (ng/mL) 69 74 69.4 0.89-8.78 Source: Own elaboration. ataxia telangiectasia: a diagnostic challenge The child was assessed by the Pediatric the findings on physical examination and the 113 Immunology Service, which considered cellular associated comorbidities. and humoral immunodeficiency (IgG2 and At the time of preparation of this case report, IgG4 deficiency), so she started treatment the patient had undergone a global evaluation with gamma globulin IV every 28 days. She of the disease (AFP levels, immunological was also assessed by the pediatric hema- tests, video telemetry and blood counts) which tology-oncology service due to bicytopenia showed, on the one hand, an adequate response (leukopenia+thrombocytopenia) during a to the treatment and, on the other, the absence hospital stay without evidence of neoplastic of new alterations or comorbidities. It is worth alteration. The patient continued attending mentioning that, despite the poor and uncertain child psychiatry and physical, occupational prognosis that AT usually has, the child did not
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