Open Access. Published by JICNA on 31 May 2020 - aeahg iko eeoig(anyhmtlgcl ma- hematological) (mainly developing of risk high a have with Patients A-T [3]. mellitus recurrent diabetes and including infections, disease sinopulmonary tract respiratory deficiency, 10 telangiectasia, immune of oculocutaneous non- include of age presence that the the features by around neurological characterized bound is A-T wheelchair walk- Furthermore, are years. independent patients of Most loss ing. to leading peripheral progressively and neuropathy apraxia, oculomotor disorders, hyper- movement with pic- kinetic ataxia, neurological cerebellar childhood-onset The early [2]. includes control ture mutations cycle pathogenic cell and by processes ( caused repair mutated is A-T disease the The in 40,000-100,000 in [1]. 1 of births incidence live estimated an with disorder tem multisys- neurodegenerative rare, a is (A-T) Ataxia-telangiectasia BACKGROUND availability, necessity, diag- medical of on Kewords: overview based narrative complex options a and different give rare prioritizing to a by aims with settings, guideline patients resource-limited opinion-based serve costs. of in expert and therefore management A-T This can and of challenging. and diagnosis management extremely A-T settings, and be with nosis resource-limited may patients In A-T in as disease. increased such the are disorder for ionizing levels marker to alpha-fetoprotein diagnostic hypersensitivity Serum a and as picture. risk malignancy clinical increased the mellitus, complicate diabetes telangiectasia. radiation oculocutaneous failure, and growth neuropathy, disorders, disease, movement pulmonary hyperkinetic the Immunodeficiency, syndrome, in cerebellar mutations onset to early an linked with disorder generation recessive autosomal an is (A-T) Ataxia-telangiectasia Abstract 2020 31, May Published: 2020 26, May Accepted: 2019 16, Nov Received: MD; [email protected]. Os, E-mail: van J.H. Nienke author: Corresponding 8 7 6 Netherlands 5 The Nijmegen, Netherlands center, The medical Nijmegen, center, medical university Radboud Sciences, 4 Life Molecular for Institute 3 Netherlands The Netherlandsy The Nijmegen, center, 2 medical university Radboud Behaviour; 1 Warrenburg de van P.C. Bart Os van Settings J.H. Resource-Limited Nienke in Ataxia-Telangiectasia of Management and Diagnosis Neurology Child in e-journal access open reviewed peer A JICNA eateto eiti erlg,Rdodm mlaCide’ optl odr nttt o ri,Cgiinand Cognition Brain, for Institute Donders Hospital; Children’s Amalia Radboudumc Neurology, Pediatric of Department eateto eiieadPdarc,KlmnaoCrsinMdclCnr,Msi Tanzania Moshi, Centre, Medical Christian Kilimanjaro Pediatrics, Malaysia and Johor, Medicine Hospital, of Ismail Department Kingdom Sultan United and London, Hospital, College, Specialist University Neurology, Puteri Brazil of Paulo, Institute São UCL (UNICAMP), Unit, Campinas Education de Estadual university Universidade Neurology, Radboud of Hospital; Children’s Department Amalia Radboudumc Pulmonology, Pediatric of Department – Radboudumc Pediatrics Hospital; Children’s of Amalia Department Radboudumc Immunology, and Disease Infectious Pediatric Nijmegen, - center, Pediatrics medical of university Department Radboud Behaviour, and Cognition Brain, for Institute Donders Neurology, of Department https://doi.org/10.17724/jicna.2020.181 txatlnicai,rsuc-iie,gieie multisystem. guideline, resource-limited, Ataxia-telangiectasia, ® | 1 ora fteInternational the of Journal , hl erlg Association Neurology Child 2 ATM onJ a Aerde van J. Koen ; ee hc ly r oei DNA in role are plays which gene, ) 2 or ..Weemaes M.R. Corry , 3 uihvnGaalen van Judith ; 3 aik .Dekker C. Marieke , 2 ee .Merkus J. Peter , 1 lomnfssi hs ra iharltvl ihconsan- high relatively a A- with that areas imply these Asia in South manifests Central also and coun- T East rich North Middle from resource reports the However, from Africa, America. are North challenging and papers Europe is A-T in tries A-T of of majority distribution the since global the of Determination on A-T. focuses of much paper form its this classic reasons, of are the practical Because A-T for 6]. and of [5, incidence, forms higher decades of- for variant, patients undiagnosed these or phenotype; remain classic the ten Milder, the than beyond rarer survive [4]. are but not life known, will of A-T decade are with systems third healthcare patients full-facility most modern, parts available, where those world in the Even of pro- complications. disease by disease-related caused and problems gression medical with of ra- patients multitude and a nutshell, face a radiation A-T In ionizing drugs. to chemotherapeutic hypersensitive diomimetic are and lignancies 8 aik .Dekker C. Marieke , 4 ar Silveira-Moriyama Laura , ATM ee n scaatrzdb neurode- by characterized is and gene, 1 sNJH ta. ieseJICNA. licensee al.; et N.J.H. Os © 5 , 6 au .Tajudin A. Tajul , 7 , Open Access. Published by JICNA on 31 May 2020 lnclclues Clinical 1). Table (see diagnosis other differential out the rule in as listed well are that as the disorders abnormalities confirm serum can classic which of below) presence cheap (see and blood simple in relatively measures using laboratory presumptive made a A-T, pic- be of can clinical suspicion diagnosis clinical the clinical high on a based with cases suspected In be persons ture. can rural however, for A-T, reach logistic to [15]. and difficult scarce, services genetic are com- make counsellors ser- insurance reasons genetic by these addition, covered access, In not with (e.g., panies). unaffordable countries the be In in Sub may mutations vices in unavailable. for example is testing for gene genetic ATM resources, molecular limited Africa, with Saharan countries most In DIAGNOSIS A-T. with familiar profes- less to are care secondary who health in hospitals, help level particular to tertiary in order settings, in resource-limited done’ in be sionals done’ to be needs can ‘what ‘what and between make to distinction tried opinion-based have expert We an on costs. based and be availability, can necessity, decisions medical case-by-case differ- individual prioritizes so and options limited are ent of resources management where and settings diagnosis in A-T the practical both a give of overview to narrative aims to and guideline access current and The of availability resources. full medical with these settings since privileged worldwide, to implemented guidelines apply be cannot treatment 14] published 13, [9, hitherto A-T for Therefore, settings 12]. resource-limited 11, of in [10, causes treatment and known un- diagnosis are problems, of suboptimal poverty social Lack and times, waiting A-T. infrastructures, long derdeveloped as and unavailability tests pa- such coverage, diagnostic of diseases of insurance and groups rare professionals es- and vulnerable healthcare but complex for general, with care in tients specialized settings resource-limited about may in pecially care challenge medical a adequate of be affordability and availability The in [9]. care experts and rehabilitation of oncology pulmonology, immunology, team neurology, multidisciplinary of prefer- fields dedicated are the a patients by A-T treated setting). ably therapeutic and both (in diagnostic the radiation prevent the ionizing may or and chemotherapy death), malignan- full-dose of to or causes exposure disease major both lung develop- are as the (which such for cies awareness problems, increases secondary it of coun- time ment family same adequate the to ends at contributes diagnosis selling, and the uncertainty that fact of the period from a Apart di- important. timely A-T, is for agnosis therapy curative no currently is there Although underre- lim- of be result must resources. a A-T healthcare as ited possibly logically, here, More underdiagnosed) (and/or not ported regions. does these A-T that in suggesting the erroneously occur of 8], parts [7, resource-limited scarce most are the world from Reports rate. guinity a SN ta IN 00 1:1 2020, JICNA - al et N. OS van 2 vnrrrta -)a el(e al ) ic F safetal a is AFP Since 1). Table (see well as are A-T) (that syndromes than ataxia rarer other even some However, in suspected. increased is be can A-T serum level if the its Testing recommended [19]. highly 1,000 age is to with level patients increase 20 AFP and from all [18] range in A-T levels in AFP ng/mL) ng/mL Serum A- (>10 [17]. for increased A-T biomarker are classic with levels blood serum important since most T the considered is AFP (AFP) Alpha-fetoprotein clues Laboratory malignancy. undiagnosed a an develop with who malig- children disability of in neurological risk suspected increased be to should leading A-T nancy, repair DNA defective to Due Malignancies developing of risk higher a [16]. cancer) have breast mutation (especially malignancies ATM heterozygous an and patients of A-T carriers both be as can families, cancer A-T of in prevalence increased the Furthermore, of case sibs. in affected or more therefore, parents consanguineous should, with families and in suspected recessively be autosomal transmitted is A-T history Family in visible already skin, the hairs of grey toddlers. of) hypopigmentation numbers or (small hyper- as and manifests A-T repair) with years DNA children defective four of in feature approximately a eyes of (as ageing the age Premature in the onwards. from visible skin telangiectasia, sun-exposed have and patients A-T all Almost abnormalities eye and Skin the spas- of Importantly, hallmarks no years. are disease. disability the intellectual over and progressive epilepsy ticity, are A-T abnormal- Motor in teenagers. ities in apraxia oculomotor chil- severe abnormalities, younger to in dren movement nystagmus gaze-evoked eye the isolated have an of from A-T stage ranging with end Anterior the Children at emerges disease. extremities. generally distal involvement the cell horn at disappear- and dysfunction the weakness, and with skin wasting life, autonomic muscle of distal decade reflexes, tendon first of the ance of usually end is the involvement by system and evident nervous choreoathetosis peripheral (mild) The as dystonia. such disorders hyper- with movement parents together hardly appears kinetic Most is but A-T, ataxia in symptom Cerebellar walk. isolated an to falls. ever begins cerebellar frequent and child exhibiting clumsiness the children notice when all arises in that suspected ataxia be to needs A-T features Neurological Open Access. Published by JICNA on 31 May 2020 ss hwn hoooa ntblt n :4tasoain in translocations 7:14 and instability chromosomal anal- showing Cytogenetic investigations. ysis, of types these world- be perform laboratories can that few ATM wide a of only function are there and but A- presence additionally, of the analyzed work-up level, diagnostic protein the the in At standard T. gold muta- the gene ATM is services, analysis genetic tion with contacts on rely can one If analysis Molecular patients A-T of [7]. report diarrhea A frequent mentioned A-T. described Mali of as from suspicion features raise should neurological sinopulmonary above, with recurrent of combined not presentation infections are clinical immunodeficiency of the detection available, the for tests devel- laboratory lymphoma If of signal ele- a An be also [4]. opment. can prognosis level poor IgM a serum have patients vated phenotype A-T IgM. IgM serum hyper com- of a deficiency levels with elevated IgA to and normal IgG with serum bined a comprising recom- and switch class bination, defective ‘hy- from so-called resulting the phenotype’, have IgM A-T per with patients reach. of within 10% be Approximately not often may polysaccha- tests these pneumococcal will but to A-T vaccines, with responses ride Patients antibody smear. low blood have a most by lymphope- also identified In by be accompanied can treatment. are as numbers HIV nia, CD4 of low A-T, context of viral the cases HIV in and facilities CD4/8 testing free load World States provide the United (WHO) and Organization the (USAID) Health countries, Development some International In for in Agency Immunodeficiency prevalent. reach is within Human often (HIV) the Virus is where testing CD8 CD4 and settings A-T. CD4 resource-limited with of patients numbers IgG low in IgA, and cells an deficiency reveal subclass may IgG2 tests laboratory or available, If and patients life. during between cel- variable and although humoral immunodeficiency, combined a lular have A-T classic with patients Most Immunology findings. laboratory or within clinical placed key be additional to of need context findings the these suspicion However, higher disease. a this to of rise of give presence may the transaminases occur general), serum frequently in elevated (that settings co-infections resource-limited of in sign people a in be pu- can specific from not and A-T, are patients abnormalities for these A-T While in 21]. [20, elevated onwards berty be can aspartate (AST)) and transaminase (ALT) transaminase (alanine transaminases Serum function Liver blood affordable and simple relatively measure- The a is [18]. test. AFP life of serum years of two physiolog-ment first gradually are the and levels in AFP serum, ‘elevated’ serum fetal ically Therefore, in levels birth. high after in declines present is it protein, a SN ta IN 00 1:1 2020, JICNA - al et N. OS van 3 res eeo sbaue n aeamr ai progression rapid more onset a dis- have childhood movement and early hyperkinetic (sub)acute, other an develop by have ac- orders, accompanied not most not do example, are an ataxia and give of To causes in- helpful. quired neurological) patient’s very (including the be physical disorders, will careful acquired vestigation a these as of well many as In history and out. should post-varicella) ab- ruled disease HIV, be vascular (para)neoplastic deficiency, or (e.g. auto-immune/demyelinating child- vitamin disease (in alcoholism, infectious ataxia of normalities, as causes acquired such certainty, of hood), lack of case In detail. more disorders), in these these certain with discuss patients Since not in rare will elevated we extremely not 1). are is Table AFP disorder (see serum A-T-like (and A-T like than disorders rare repair AOA all DNA more and far A-T, AOA with are with patients types patients to of compared levels lower generally AFP serum are by increased serum or The A-T albumin from levels. serum characteristics, cholesterol low distinguished laboratory signs, be and pyramidal can as clinical such 4 both and account apraxia 3 into oculomotor taking 2, with 1, ataxia types and (AOA) vita- (AVED), with deficiency ataxia E ataxia), min recessive (considered autosomal (FA) prevalent ataxia most Friedreich the as here. cerebral helpful such be ‘ataxic ataxias will genetic taking with Other history misdiagnosed careful but be CP), (ataxic may palsy’ A-T with Patients differ- diagnosis. the dis- narrow ential to other crucial The are features above. non-neurological described tinctive signs as neurological abnormalities typical few laboratory the a and of only However, combination a broad. feature is disorders A-T of diagnosis differential The diagnosis Differential in radiosensitivity increased patients. the high A-T given a A-T, with cases of for suspicion be harmful be only clinical to not likely may is (CT) it but tomography cost-ineffective, im- computed is that It note basis. to case-by-case (see a portant diagnosis on differential considered be the should in in and below) listed helpful be disorders may other they out or A-T, of ruling paramount diagnosis not the confirm Although to involvement sufficient respectively. cell disease), horn advanced anterior in (with neuropathy peripheral findings atrophy) clinical and cerebellar confirm unspecific (showing will in dysfunction EMG cerebellar normal of and are MRI LP A-T. and necessary EEG with not A-T. patients of are of diagnosis diagnosis and assay, the the establishing AFP in for serum cost-effective to be compared when to A-T unlikely are electroencephalogra- (EEG) and diagnos- resonance phy (LP), expensive magnetic puncture lumbar (EMG), and (MRI), electromyography invasive imaging as that such forward tests put tic to want We investigations neurological Ancillary confirma- definite diagnosis. than the (rather of) to tion expensive, clues generally additional offers is only facilities, and laboratory other requires A-T, Open Access. Published by JICNA on 31 May 2020 eorelmtdstig o nyb aaooyadntendo- not and laparotomy in by available only easily (or be settings not may resource-limited language placement feeding speech-and or Gastrostomy nutritional accessible, additional advices. If give be- may fatigue dieticians rested [32]. or Since be meal therapists a should 32]. have patients [9, they intake, straw fore oral a suboptimal of cause use can the avail- easy and be everywhere) not may able this liquids facilitate thin to of products thickening special portions, (although bite-sized foods in chewable into good supported food easy a cutting of is or use to patient swallowing), safe the attention optimal that pay for (so seating to meals are during intake position sitting improve to tips Practical of be to 40]. [38]. found [39, also children importance is major caretakers these the of of support on and effect composition training good Adequate body a features and had clinical status support of nutritional nutritional severity Adequate and 37]. poverty malnourish- [36, by settings, resource-limited augmented cerebral in is as that ment such known disorders is neurological it palsy, other with patients For first. tackled be should that A-T believe in we problems Therefore, nutritional symptomatic suboptimal. be Without other will of A-T 35]. effectiveness for 34, treatments the 33, status, [32, nutritional growth good abnor- their a endocrine impede prob- also and oral-motor can chewing), and malities may and fatigue, they swallowing to affecting that (due lems disadvantage eat additional to patients the struggle settings, physically have resource-limited may in foods A-T acquire nutritious with to that neu- difficult problem the be of Besides can resource- progression is in [31]. the problem It major settings in a limited is role mortality. and considerable [30] and diseases a rodegenerative burden play disease to increased general, known to in factor leads prognostic which unfavorable an is Malnourishment endocrinology / Nutrition medicine. X-rays, nuclear ra- as and such ionizing tomography tests avoid diagnostic to of made avoidance be with diagnosis starting should diation, presumptive effort impera- every or is made, confirmed is it a A-T harm”, of once no that do highlight ‘’first to of tive rule golden the in Following radiation ionizing Avoid FOLLOW-UP AND TREATMENT INCLUDING MANAGEMENT ataxia. [22]. subtypes of SCA forms of representation prevalence schematic these global a the with published of serum recently patients rule, al. in et a normal Klockgether As are fam- affected. levels in are AFP and generations signs multiple pyramidal iso- where with with ilies combined cases ataxia spastic in considered ataxia, and be lated should episodic disorders and in- These (SCA), ataxia ataxias. of ataxias causes spinocerebellar inherited clude dominantly Autosomal A-T. than a SN ta IN 00 1:1 2020, JICNA - al et N. OS van 4 cloi.Frrcmedtosrgrigtedu ramn of treatment to drug predispose the may regarding which recommendations hypotonia For axial scoliosis. of worsening slow- cognitive and including effects ing [9] side costs for and monitored availability properly of and order in other prescribed effective, be or can not tetrabenazine gabapentin dopa-responsive is mimetics, GABA this a anticholinergics, If as and such drugs [43]. A-T described with been levodopa patients have with some dystonia trial since a on, recommend early we dystonia, generalized For dystonia. standing which long deformity in secondary common decrease is sensory will of use rehabilitation good in injections, and tricks exercises toxin stretching botulinum Simple by available. attenuated if be patients. can between dystonia substantially Focal vary severity and but distribution present, often to the trou- is most Dystonia ability A-T. the in potentially disorder the a movement is blesome including of dystonia aids opinion, reduction of our In use impressive wheelchair. the to necessitates and leads independently of it move irrespective that disorder, movement generally fact their patients the prescribe about important, to complain more mindful even not be and do to that, may Above recommend costs we these. while Therefore, problematic, low high. be is be may A-T availability in – moderate; disorders experience effective- movement to the for our addition, pharmacotherapy in In of – ness therapy. and drug necessitates care, complications ever supportive hardly their of and mainly features consists neurological of treatment The rehabilitation / Neurology or tests diagnostic settings. resource-limited additional in these require treatment and not A-T, in therefore concerns may clinical features major to lead don’t failure, generally gonadal and hyper- deficiency as hormone such A-T, growth in cholesterolemia, reported are that prevent problems endocrine to Other effective be may D vitamin fractures. or Supplementation calcium important. estrogens, are of intake proper calcium status are dietary when nutritional good healthy who particular and A in patients early. [33, provided and older not A-T [42] was in rehabilitation years with problem for a patients bound be in wheelchair can common Osteoporosis are levels 35]. D vitamin Low may [41]. settings diabetes resource-limited for in medicines problematic essential be avail- of most The affordability in sporadically. and occurs diabetes ability only treat resistance to insulin and sufficient cases, HbA1c is Oral serum metformin important. elevated with more of in treatment even levels case becomes available) guidance In nutritional if levels, Screening). HbA1c (see (or reg- cases glucose advice these serum therefore We of testing 2. they type ular adulthood, mellitus or diabetes adolescence develop into may survive A-T with patients tempo- If is placement recovery. the boost cases to these only to and in important rary that is parents It for out infections. stress from malnour- recovering of cases when severe and in solution ishment a be may naso- feeding temporary tube or gastric drinks, and food protein-enriched but scopic), Open Access. Published by JICNA on 31 May 2020 in dcto,atboi pohlci)teay n adequate and therapy, (prophylactic) vaccinations. condi- antibiotic physical education, optimizing tion, include settings infections these resource-limited of in occurrence in- infections. the sinopulmonary decrease occurring to mild commonly measures are Common A-T most with The patients generally A-T. in not fections with do patients infections in opportunistic occur and systemic Severe, Immunology pa- in communication for tool dysarthria. severe physiotherapist. helpful a a with a of tients be help can the phones with Mobile implemented routines be exercise also simple in- should with pulmonary rehabilitation decreased to Respiratory Scoliosis predisposes fection. further cough. and inadequate expansion an pulmonary sco- and reduce that to choking, essential (wheel)chair is de- liosis, A position children sitting neuropathy). upright most good peripheral that a of provides drop result foot a bilateral as the velop for (which helpful such orthoses devices, be ankle-foot aid can and as frames, even standing scarce, very wheelchairs, units be as special may or school needs, general a special addi- at with In children for accessible. institutions easily tion, most often set- are resource-limited physiotherapists these between tings; of and accessibility within the vary or that may fact contractures professionals the as of aware con- such are We and complications dysphagia. these function of of prevention physical goal and of main dition, maintenance The the is specialist. interventions rehabilitation and therapists a language available, least and if speech at physiotherapists, and is as therapists, care such occupational this professionals care that health family nevertheless by their imperative supervised of is responsibility It the often members. of care is daily patients the ill settings, resource-limited chronically in that known well is It gabapentin tried. be baclofen, can but 4-aminopyridine nystagmus, or treatment and successful apraxia for evidence oculomotor limited of is There treatment published [9]. previously our guideline my- to chorea, refer we ataxia, tremor, as or such oclonus, A-T, in symptoms neurological other 1 Table txcCP Ataxic SCA ( AOA4 ( AOA3 ( AOA2 ( AOA1 ( AVED ( FA ( A-T (gene) Disease FXN ATM PNKP PIK3R5 SETX APTX TTPA ifrnildansso A-T. of diagnosis Differential ) ) ) ) ) ) ) Neonatal yrs) range (25-50 Wide years <10 years 12-18 years 3-30 years 2-10 years 5-15 years 10-16 years <2 Onset - - (<60) + / - (<100) + stable) (<60, + stable) (<60, + / - - - 19 [18] (ng/mL) AFP serum Increased a SN ta IN 00 1:1 2020, JICNA - al et N. OS van ------+ deficiency Immuno 5 osac o eodr neligcue lk HIV). (like causes advise underlying we secondary immunodeficiency, for uncommon) search to rather signs Fur- with we (i.e. settings positive, possible. severe resource-limited HIV as of in be soon patients to A-T as found in therapy is thermore, antiretroviral A-T start with to patient progno- suggest a the poor case in a have In described patients been these sis. assume not We have far. thus A-T literature with patients positive HIV and costs. mandatory the outweigh not not is do IVIg effects an deficiency, the with IgG2 patients and/or re- In IgA antibody isolated [44]. in specific immunizations or low booster phenotype, despite and IgM sponses infections hyper recurrent a immunodeficiency with 4g/l), severe < patients (IgG a most deficiency with is IgG this patients with believe in we indicated settings. possible, is resource-limited strongly substitution in IVIg affordable periodic nor If available be not of- ten may therapy substitution (IVIg) immunoglobulin Intravenous effect. immunomodulatory suggested [14]. effects a account Side has into Azithromycin taken used. dose be generally should single are resistance a week) microbiological (in and a Azithromycin times and three mg/kg) 10mg/kg 18 of of sin- a dose (in daily Co-trimoxazole 30mg/kg/day), gle Amoxi- of infections. dose severe single a or (in recurrent cillin avail- with patients if A-T considered, in be able, should treatment antibiotic indi- Prophylactic seldomly is lavage Broncho-alveolar nasal/pharyngeal cated. or suffice. sputum will man- investigations, further swabs these guide to For order in obtained agement. results be should resistance PCRs with viral first and cultures at (myco-)bacterial mild antibi- treatment, seem following sufficiently can otic improve not that do infections, patients When these sight. prolonged of a course prevent severe to or order with in patients to function, compared immunological should sooner normal treatment or antibiotic easily more A-T administered with be patients in cough, that doctor. fever, a believe We contact to (e.g. when symptoms advised be ‘alarm’ should about and dyspnea) of aware should made families patients their with be and discussed patients Furthermore, be to families. their need and infections of risk to the regimens decrease hygienic immunodeficiency, an with patients A-T For - - - + Telangiectasia ------+ risk Malignancy - - - - - AR AR AR AR Inheritance o genetic Non AD AR AR AR eu oa hlseo [25] cholesterol total serum increased Hypoalbuminemia, [24] signs dal E pyrami- problems, vitamin visual level, plasma Reduced [23] cardiomyopathy opticopathy, sings, Pyramidal text See features distinctive Other yaia in,static signs, Pyramidal [29] gene SCA on depending features other signs, Pyramidal [28] elevated cholesterol Hypoalbuminemia, [27] described) are Saudi family in Arabian patients 4 (only Rare signs[26] Pyramidal Open Access. Published by JICNA on 31 May 2020 rsrbdo nossetadnneiec-ae rtra and criteria, non-evidence-based and frequently inconsistent of are on antibiotics loss prescribed prophylactic progressive Therefore, and function. develop- bronchiectasis lung the of to progression not contribute do and older infections infections ment recurrent in opportunistic but common rare A-T, rule, more in a occur are As aureus 53]. S. [52, influen- and children H. in as Pneumoniae, pathogens such S. common bacteria zae, with are infections Viruses and childhood, prognosis. early poor risk a and for comorbidity significant disease. factor a lung is intrinsic malnourishment of ef- addition, In presence cough the to and neuro- ability aspirations, fectively, chronic impaired immunodeficiency, of disease, consequences are they logic pulmonary since the especially lungs, with the combined to threat antibiotic permanent con- intravenous a nature require stitutes recurrent their not However, se- generally hospitalization. rarely or do treatment are and infections A-T tract set- in respiratory resource-limited vere lower in and disease infections upper of burden tings, respiratory high Although very a neu- [14]. constitute to coughing and due swallowing and abnormal aspiration breathing, weakness, and like pathogens impairments of rological stasis pulmonary disease/fibrosis, the and recur- lung of of result interstitial a combination (as immunodeficiency), a infections underlying by tract respiratory caused lower is and wheeze upper A-T rent and in congestion disease Lung dyspnea, sus- cough, [42]. be with can patients progres- problems in often pulmonary pected Clinically, and A-T. chronic of major, feature sive a is involvement Pulmonary Pulmonology A-T. with patients all in pneumococcal vaccines years) five 13-valent polysaccharide (every and pneumococcal 23-valent year) and (every conjugate vaccina- vaccine recommend flu we with available, A-T tion If in complications vaccination. these after describe we that patients although reports of 51], aware [50, not decrease complications are to vaccine-derived order of cell in risk CD4 lymphopenia, the immunodeficiency, or severe vaccines 500/mm3, a below attenuated have numbers live that give patients to A-T not to recommend we [49]. Therefore, challenging extremely is with treatment patients their all and of note, [48], 10% Of to A-T up in- 47]. in to [46, occur may granulomas thought granulomas of cutaneous is development vaccine for risk Rubella the the crease phenotype), deficiency IgM (IgG immunodeficiency hyper severe or a with A-T. patients with A-T patients In all complications. in safe or are trouble sus- vaccines without inactivated even Importantly, goes is normally A-T this before and administered [45]. pected, are virus vaccines Papilloma these Human of Most and Rubella, Measles, conjugates, Rotavirus, Per- Pneumococcal Tetanus, b, type Diphtheria, influenzae Polio, Haemophilus tussis, recom- B, Hepatitis vac- are include BCG, WHO that against the cines immunizations by programs Routine immunization all for availablemended setting. only private or the some unavailable In be in may country. vaccines per certain all differ immu- countries, programs routine that These National advise in programs. we participate nization exist, should rule A-T the with children to exceptions some Although a SN ta IN 00 1:1 2020, JICNA - al et N. OS van 6 ramn cu fe nrsuc-iie etns[57]. settings in- of resource-limited abandonment in health and often be mortality occur related treatment not treatment may and majority all), countries at the sured resource-limited (and treatment [55] in insurance cancer patients health of further of by costs is covered that not This often facts are general 56]. the settings [55, by resource-limited difficult complicated in extremely A-T doubt any with without of patients treatment the in effective and make malignancy will delay) a handicap treatment physical a and of neutropenia presence like- infections, higher of a (with lihood malnourishment pre- treatments, delayed access and limited diagnosis addition, stage, to In disease advanced subsequent defect. with repair sentation DNA due drugs, underlying cytostatic the certain to increased and an therapy by radiation The complicated for is sensitivity A-T settings. in resource-limited malignancies of in an treatment suggesting survival [4], worrying diagnosis more cancer sur- their even generally after year patients one In these only poor. settings, vive is facility malignancy full a and with A-T countries with children of prognosis The diagnostic the that during high early so is seriously workup. A-T considered in be lymphoma is should or setting they leukemia resource-limited for a in risk child the a broad, differen- in the anemia Although of diagnosis tumors. tial solid lymphoma than and frequently more leukemia occur as A- such with malignancies children In hematological cancer. T, develop to prone are A-T with Patients Oncology status. pulmonary high-tech the in of impression underestimated an or provides overlooked environments, rates, easily respiratory be and may heart- which of Obvi- observation clinical dysfunction. simple ously, pulmonary obstructive some- with capacity), a combined have vital patients forced times low most a experience, (explaining our pattern In restrictive avail- [54]. not hospitals still all but in affordable able and spirom- accessible here, easy described relatively tests is func- diagnostic etry lung other true to underestimate Compared often tion. will insight mus- ataxia few gives to and due that a weakness discoordination alternative cle however, within good status, available pulmonary a the likely be into is may the Spirometry care of MRI patient years. of routine Modifications for effective. cost lungs these and is easy auscultation is Pulmonary patients available. become tech- should imaging or all alternative are CT if that niques or especially sensitivity X-ray possible, by radio when imaging avoided increased be lung the express, Given A-T with patients A- challenge. in a function is and T structure pulmonary of monitoring Adequate [14]. monitored such be effects, should side osteoporosis, of and emergence diabetes ad- The as when effective onset. only are after but soon [14] ministered cases these corticosteroids in who Oral helpful antibiotics. symptoms should be with may It respiratory treatment A-T. to with respond with children not patients do older young in in suspected concern be primary and a A-T, usu- not with so, patients if is in and onwards patients adolescence of from minority emerges ally a Intersti- in develops countries. disease and lung centers tial between considerably varies this Open Access. Published by JICNA on 31 May 2020 ioie( omo iai 3 nAT fwihterslswill [61]. results year the this which of end of A-T, the nicotinamide in at of available B3) effects become vitamin the of study form we to (a example, trial riboside an a As running currently ar- available. are resource-poor become in may strategies disease-modifying located cheap treatment those relatively to even to and willing simpler also be Finally, may eas. sites companies trial since the relevant be extend treatment steroid trials, may of Industry-driven [60] effects A-T the with [59]. exploring A-T, in case trial for ongoing single horizon an a the as in such on ongoing is trial elabo- therapy first Gene briefly in a should patients topic. we for this reach on that rate of feel out we be settings, settings, generally research resource-limited will in therapy, A-T gene for like therapies novel possible Although therapies Novel ma- of are measures importance. infections hygienic jor wound perioperative develop so to [58], risk surgery patients after at sta- A-T more nutritional Immunodeficient be good theoretically [58]. would in surgery after patients and keep before to tus pre- and made [57] outcome, be desirable adverse is should of status efforts risk pulmonary the the of decrease resource-limited screening in to operative option order anes- safest In Local the is settings. acceptable. this as are re- preferred, life of is chances of thesia if quality conducted expected be and only covery should resource- and in patients settings, A-T limited in considered dedicated well a very be (in should surgery clinic) Therefore, post- peri-and [57]. of may risk complications increased ventilation operative at mechanical are A-T, patients and with challenging, patients be in particular common in are origin - pulmonary of - problems multisystemic Since care critical and anesthesia Surgery, [55]. palliative timely settings, initiated resource-limited be in should care cancer pa- and every almost A-T in with case tient the be not unfortunately is will treatment cancer which curative possible, positive, case In HIV control. are pain who adequate and patients in A-T therapy immunodeficient antiretroviral optimizing in prophylaxis patients, parents, of and use the patients status, of course. nutritional support disease the social in includes early This embedded choice. be of should treatment care final Supportive the in role or a social play Additionally, may reduced. factors be financial should dosages should global or drugs lym- avoided radiomimetic a and be and is leukemias radiotherapy general, pediatric I-BFM In on phomas. research available. evidence-based doing are no group A-T currently working for and A-T, protocols with treatment Inter- threat- life patients thus Group (and for the toxic hematolog- too ening) Working far consult be a may Variation protocols standard to since with opinion, Genetic expert consider diagnosed their (I-BFM) for (www.bfminternational.wordpress.com) may is BFM A-T one national with malignancy, child ical a When a SN ta IN 00 1:1 2020, JICNA - al et N. OS van 7 nldn elh it hudb cieypooe ytetreat- the [64]. by physician promoted actively ing be and should smoking, diet) (without healthy a lifestyle including mammogra- healthy than a Furthermore, cheaper is [64]. phy and breast Clinical beneficial, [63]. be effective may cost examination most treat- are cancer and breast detection testing of early cancer, genetic ment Importantly, on other) [15]. than (or carriership rather ATM breast treatment for to of access detection optimal carri- early on (possible) and on of focus management should [15]. the ers coverage that insurance believe we or Therefore, employment losing con- unwanted like and unexpected sequences have found may is this ATM member, like family gene a in susceptibility cancer breast a a if in Furthermore, gene mutation ATM settings. the resource-limited in in unavailable mutations often is for screening genetic mentioned, As carriers Screening ab- or infections generally years. is the recurrent A-T over of in stable Lymphopenia case levels. in IgG (decreased) intensified normal be to years, need two every but done be should immunodeficiency for Screening should A-T of and diagnosis considered. malignancy the seriously a well, be as with disability presents neurological child a a has if around, way exposure. other radiation of The but because important, avoided is be patients lymphadenopathy. should female mammography and adult organomegaly in screening additionally of these cancer of Breast should presence one the examination if on Physical doctor focus the contact emerge. to instructed symptoms swellings. be or to pain localized need or They abnormalities skin devel- new the of and opment pain, bone bruising, loss, easy weight and fatigue, bleeding fever, spontaneous made as be such should symptoms’ ‘alarming families of and aware Patients follow-up effective. clinical equally close possible, be not might is Ta- screening (see of annual disease If development pulmonary 2). the ble and for liver and screening diabetes annual malignancies, advise we possible, If patients Screening SCREENING [62]. beliefs religious or genetic cultural of by inaccessibility and knowledge, services, of can lack counselling a by cardiovascular such complicated settings, and be resource-limited cancer, In (breast) are [16]. develop mutation diseases to ATM risk pathogenic A-T. increased a with risks, at of child health carriers own their their heterozygous of to since siblings alerted be (future) recurrence should in a carriers 25% carri- with Furthermore, of thus heterozygous A-T mutation, be of gene to ATM risk likely pathogenic a both be of are must ers Parents they disease. that recessive aware autosomal made the an on is focus A-T should that members fact family and patients of Counselling COUNSELLING GENETIC Open Access. Published by JICNA on 31 May 2020 al 3 Table 2 Table Immunodeficiency disease Pulmonary disease Liver Diabetes malignancy (Hematological) for Screening lnclimplications. Clinical A-T. in tests screening Routine htntt do to not What indicated) if patients, some (in done be can What patients) all (in do to What l ages spirometry All of capable are who Children Adults Adults Adults Adults Adults Adults ages All age From a SN ta IN 00 1:1 2020, JICNA - al et N. OS van 8 ain ihteayadaddevices aid and therapy with cations compli- prevent and condition Increase status nutritional Improve level AFP serum test: Diagnostic rg)sol elmtdt atre- last adapted to be can dose limited and source, be should (CT,drugs) radiomimetic radiation therapy, radiation ionizing X-ray, to Exposure diag- differential nosis broad out not rule and to indication should only proper without LP) done EMG, be EEG, (MRI, tests diagnostic invasive and Expensive pos- sible if only carriers, for testing Genetic with consequences deficiencies clinical proven by if indicated only immunoglobulins, Intravenous oc- cur infections (bacterial) severe or recur- rent if only antibiotics, Prophylactic of case the dystonia in relevant only seems ders disor- alarming movement for Pharmacotherapy about symptoms information Give visits annual Plan families of Counselling malig- of case nancy in care palliative Early complications prevent to infections of treatment Early programs vaccination national Follow g,wiebodcl count cell blood CT) white or IgG, X-ray (no test function Lung ultrasound Abdominal transaminases Serum Glycosuria HbA1c glucose, fasting Serum mammography) (no screening cancer Breast IgM ultrasound smear, Abdominal and count blood LDH, Serum Tests Open Access. Published by JICNA on 31 May 2020 nrsuc-iie etnsoesol nwthat: know should one settings resource-limited In MESSAGES KEY So- ‘A-T Project’ the Children’s ‘A-T of (www.atcp.org). websites the the and via (www.atsociety.org.uk), possible ciety’ is other contact English, to in opportunity families the and A-T about information De- via tailed advice ([email protected]). for available email are and professionals, websites care health A- as with well patients as and T families ‘A-T including other world, and the we around Obviously, groups’ below. listed are fields messages key the in Our oncology. 3), and Table pulmonology (see immunology, do’ neurology, to nutrition, not of ‘what done’, and be done’ be to can needs ‘what expert ‘what gives about and situations recommendations diag- such opinion-based in of overview options practical therapeutic and a gives nostic paper set- This resource-limited in make challenging. A-T A-T, tings of and on treatment knowledge pediatricians and of diagnosis alone lack adequate let a professionals, with combined care neurologists, health of lack A REMARKS FINAL AND CONCLUSIONS Cusligo aiisi motn o uuefml plan- family future for important is families of Counselling 10. We hl eeosamlgac,teponssi very is prognosis the malignancy, a develops child a When 9. dysfunc- pulmonary and diabetes malignancy, for Screening 8. vac- national regular in participate should A-T with Patients 7. Pro- A-T. of hallmarks the of one is infections Recurrent 6. drug with improve not do generally symptoms Neurological 5. com- prevent to important very is status nutritional good A 4. should diagnosis presumptive a or suspicion clinical High 3. AFP serum A-T, of clues clinical with presents child a When 2. in underreported severely likely is A-T of occurrence The 1. igadt nraeaaeeso elhpolm o both for members. problems family health their and of patients awareness increase to and ning implemented. be should care palliative and poor routinely. performed be should tion re- not better vaccines. should attenuated patients live ceive some but programs, cination cases. all, in not but some, in substitu- indicated are immunoglobulin therapy tion and therapy antibiotic phylactic pharmaco- necessitate intervention. may logic dystonia severe only treatment; disease. the of plications radia- ionizing medicine). nuclear using tomography, (x-rays, tests tion diagnostic of avoidance prompt of diagnosis presumptive a A-T. make to sufficient is assessment health specialized of neurologists. lack and to pediatricians as due such world professionals care the of parts many a SN ta IN 00 1:1 2020, JICNA - al et N. OS van 9 vial nti ril,nesohriestated otherwise made article,unless data this the in to Com- available applies Creative waiver The Dedication Domain credited. Public properly pro-mons is medium, work any of original the in terms reproduction vided unre- the and permits distribution, under which use, distributed License stricted Attribution article Commons Access Creative Open the an is This manuscript. the wrote designed and and study conceptualized the of MW version and CW, final NvO, the manuscript. for impor- the approval for gave and critically content work intellectual the tant revising to contributed authors All contributions Authors’ no have they that declare authors interests. The competing Pharma. and Bioblast if and cen- ter, decision medical support university the research Radboud or receives Hersenstichting, ZonMW, BvdW paper, from publication. this for of submit to process when any writing have the not did in funder role The Foun- organization. Twan patient the Dutch of grant a a dation, by supported financially was work This interests Competing Schoenaker, Michiel Veenhuis. Stefanie Janssen, and Marjo Anjo Strik-Albers, Riet Hijdra, Netherlands): Helma the Gerven, col- Radboud (Nijmegen, van our the center thank from to team medical A-T want university multidisciplinary We the from support. leagues (financial) Nether- their the (Veenendaal, for Foundation lands) Twan the thank to want We Acknowledgments . Open Access. Published by JICNA on 31 May 2020 Dke C,UaaS,HwetW.Nuooia letter Neurological WP. Howlett SJ, Urasa MCJ, Dekker [10] References Neurology Child International https://doi.org/10.17724/jicna.2020.181 the 1(1). of Association, Journal Resource- Settings. in Ataxia-Telangiectasia J., Limited Di- P. of (2020). Management Merkus, A. M. and J., Willemsen, agnosis & P., Gaalen, C., M. B. van Dekker, Warrenburg, M., de J., C. van Weemaes, K. A., T. Aerde, Tajudin, van L., Silveira-Moriyama, J., N. 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