Ataxia Telangiectasia : Case Report from a Rural Hospital in Nepal and Current Management Recommendation

It is important though challenging to make accurate diagnosis of neurodegenerative conditions in children and initiate the right treatment. A 14 years old boy presented with deterioration in speech, mobility and performance of daily activities and frequent chest infections over four years. Aided ataxic gait, dysarthria, stooped posture, generalised hypotonia and weakness and ocular telangiectasia were noted. We present a case of Ataxia telangiectasia from a rural hospital in Nepal. DOI:  http://dx.doi.org/10.3126/jnps.v34i2.9694 J Nepal Paediatr Soc 2014;34(2):138-140


Introduction
P aediatric neuro-degenera ve condi ons can be challenging in resource poor se ngs-both for the pa ents with fi nancial constraints, and the clinicians with limited facili es.Ataxia, not an unusual presenta on in children, can pose diagnos c dilemmas.We report a pa ent with Ataxia Talangiectasia (AT), a rare progressive gene c neurological condi on.AT, an autosomal recessive condi on, presents in early childhood with ataxia, telangiectasia (dilated small blood vessels), immunodefi ciency, frequent sino-pulmonary infec ons and increased suscep bility to malignancies 1,2,3 .

The Case
A 14 years old Nepali boy from a lower middle class Hindu Brahmin family presented with history of inability to walk independently, slurred speech, diffi culty in wri ng, and lack of independence in performing day to day ac vi es to the Paediatric outpa ent clinic in this rural hospital.He was the fi rst born of nonconsanguineous parents, and there were no similar condi ons in the family.Born at term by normal vaginal delivery in hospital, there were no neonatal problems of note.His growth and neurodevelopment was normal un l nine years.
At nine years, he developed diffi culty in walking with frequent falls and ataxia.He also developed slurring of speech and diffi culty in wri ng.A few months later he also developed drooling, diffi culty in chewing and swallowing.He had blood shot eyes and 'unusual birth marks' behind his ears and on the back of his hands when these symptoms began.The birth marks were red in colour, looked like collec on of small blood vessels, have disappeared in a few years.The abnormal ocular blood vessels (telangiectasia) persisted (Figure1).Medical opinion was sought at the me of onset of symptoms, provided no clear diagnosis.The diffi culty in walking worsened, and the pa ent became non-ambulatory at the age of 11.He also developed a stooped posture and inability to sit without support over the last 3 years.Speech has gradually worsened, and he now has a so , slow, scanning speech.Chewing and swallowing is diffi cult, and he is only able to take a so , semi-solid diet now.
On examina on he was thinly built, and appeared to have generalised was ng.There was mild drooling.He sat with a stooped posture.He had a slow unstable gait (aided by one person) with evidence of marked weakness of the lower limb muscles.Neurological examina on revealed cerebellar signs-trunkal ataxia, nystagmus, oculo-motor dyspraxia, inten onal tremor, dysmetria, dysarthria, markedly hypotonia and weakness in all limbs.All deep tendon refl exes were diminished, fl exor plantar refl exes were elicited.The cogni on was rela vely well preserved.He was a ending main stream school with addi onal support.Cranial nerve examina on revealed no abnormali es.Sensory system examina on was normal apart from loss of join posi on sense in the inter-phalangeal joints in both lower limbs.We were unable to check for Romberg's sign.Examina on of other systems was normal.Clinical diagnosis of AT was made.
Management: The diagnosis and prognosis were explained to the parents, and the child was commenced on regular mul -vitamin supplements and prophylac c dose of Penicillin-V to prevent sinopulmonary infec ons.

Discussion
AT, fi rst described by Syllaba & Henner 4 and also known as Boder Sedgwick syndrome, is one of the most common inherited causes of childhood onset ataxia.An autosomal recessive neurodegenera ve disease, its prevalence is reported to be 1 in 40,000-88,000 in the west 5 .The clinical phenotype is heterogeneous.The responsible 'ATM gene' has been mapped to chromosome 11q22-23.The ATM gene encodes a protein kinase which is the key regulator of cellular response to double strand breaks in DNA.
Ataxia and telangiectasia are the hallmarks of AT, and abnormal eye movements are universal fi ndings.Early milestones are o en normal un l the child starts walking, when ataxia manifests.Symptoms include involuntary choreo-athetoid movements, oculomotor apraxia, drooling and dysarthria, frequent sino-pulmonary infec ons, increased incidence of malignancies (lymphomas and leukaemia) and diabetes mellitus 3 .The progressive neurodegenera on occurs from the progressive loss of purkinje cells in the cerebellum and the malfunc oning of other cells 5 .In most cases, the symptoms fi rst appear before 5 years 1 .Late onset and milder variants are described where immunodefi ciency, telangiectasia, sino-pulmonary infec ons and cancer may be absent or reduced, and slower progression of the neurological signs are seen 3,6 .Our pa ent is likely to belong to the late onset group.
Serum alpha fetoprotein (AFP) and carcinoembryonic an gen (CEA) are o en elevated, Immunoglobulin A (IgA), IgE and IgG (G2 & G4) levels are reduced in these children.Reduc on of IgA, the most prominent secretory immunoglobulin in the respiratory tract, may cause the frequent sinopulmonary infec ons.IgM level is normal or elevated 3,7 .Cell lines grown from these pa ents show increased radio-sensi vity, leading to chromosomal breakage and rearrangement 8 .This causes predisposi on to risk of cancer in AT.
AT produces neurodegenera ve changes mainly in the cerebellum.It causes signifi cant morbidity, and death usually occurs from broncho-pulmonary infec ons or malignancy in early to late adolescence.Increased suscep bility in AT to ionising radia ons must always be kept in mind while ordering radiological inves ga ons.

Evaluation of the management of this case in rural setting & recommended management
We relied on hallmark clinical signs to make the diagnosis.We were able to carry out basic inves ga ons.Recommended inves ga ons include gene c tes ng to confi rm the diagnosis, immunological inves ga ons, AFP, CEA, monitoring when malignancies are suspected, and neuro-imaging (MRI) in pa ents with unusual neurological course and/or when space occupying lesions are suspected.In resource-poor se ngs, many of these diagnos c tests are unavailable.
Currently there is no cure for AT.Pa ents require suppor ve therapy which consists of physiotherapy, occupa onal therapy, provision of orthoses, speech therapy, high calorie nutri on, gastrostomy when dysphagia ensues, prophylac c an bio cs and respiratory support when required 3,7 .Advice regarding high calorie nutri on, posture and physiotherapy as well as prophylac c an bio cs to prevent recurrent infec ons and vitamin supplementa on was off ered to our pa ent.There are limited op ons for rehabilita on therapy in rural se ngs such as ours.
Pharmacotherapy has been reported to be successful in individual cases, but there is no evidence to support their rou ne use.Gabapen ne and clonazepam have been used to improve cerebellar tremors; Aman dine, Fluoxe ne and Buspirone for motor incoordina on and dysarthria; L-Dopa deriva ves and Cholinergics, for managing chorea, dystonia and bradykinesia; and Baclofen, in dealing with spas city and contractures 9 .IV immunoglobulins can be given if the level of IgA is low.

Conclusion
Careful clinical examina on can help clinicians to diagnose rare neuro-degenera ve condi ons such as AT in rural se ngs.Appropriate medical treatment, regular physiotherapy and monitoring of the progress of such condi ons, and ensuring adequate family and community support are the key components in managing these children in resource-poor rural se ngs.