Manouri P Senanayake

Mutations in ANTXR1 Cause GAPO Syndrome

The genetic cause of GAPO syndrome, a condition characterized by growth retardation, alopecia, pseudoanodontia, and progressive visual impairment, has not previously been identified. We studied four ethnically unrelated affected individuals and identified homozygous nonsense mutations (c.262C>T [p.Arg88*] and c.505C>T [p.Arg169*]) or splicing mutations (c.1435-12A>G [p.Gly479Phefs*119]) in ANTXR1, which encodes anthrax toxin receptor 1. The nonsense mutations predictably trigger nonsense-mediated mRNA decay, resulting in the loss of ANTXR1. The transcript with the splicing mutation theoretically encodes a truncated ANTXR1 containing a neopeptide composed of 118 unique amino acids in its C terminus. GAPO syndromes major phenotypic features, which include dental abnormalities and the accumulation of extracellular matrix, recapitulate those found in Antxr1-mutant mice and point toward an underlying defect in extracellular-matrix regulation. Thus, we propose that mutations affecting ANTXR1 function are responsible for this diseases characteristic generalized defect in extracellular-matrix homeostasis.

Maternal comprehension of two growth monitoring charts in Sri Lanka

OBJECTIVE To investigate the maternal comprehension of two different growth charts and to identify the group of mothers with poor comprehension. DESIGN An experimental prospective study. SETTING A child welfare clinic at the De Soysa Hospital for Women, Colombo, Sri Lanka. SUBJECTS 932 mothers were studied regarding their interpretation of the type of growth chart their infants had been allocated. A total of 413 mothers interpreted the ‘road-to-health’ chart and 519 mothers interpreted the revised chart. A validated scoring system was used to assess comprehension. The two groups of mothers were comparable. RESULTS 62.4% (324) mothers who interpreted the revised chart had good comprehension. Only 20.6% (85) mothers had similar comprehension with the road-to-health chart. Education up to or beyond grade 8 in school significantly improved comprehension. CONCLUSION The design of the growth chart has a powerful effect on maternal comprehension of growth patterns. Length of schooling rather than literacy alone is a marker of a comprehending mother. The policy implications of these findings are that governments and agencies may need to redesign parent held growth charts to achieve better comprehension by mothers.

N-acetylcysteine in children with acute liver failure complicating dengue viral infection

OBJECTIVES To describe the outcome after administration of N-acetylcysteine (NAC) to seven children with nonparacetamol induced acute liver failure (ALF) complicating dengue infection. METHODS Clinical records of children with non paracetamol induced acute liver failure complicating severe dengue viral infection, were retrospectively analysed for clinical and biochemical outcome following treatment with NAC. RESULTS Seven patients between ages six months to twelve years with plasma leakage and circulatory compromise complicating dengue infection developed ALF. Three were exposed to prolonged shock prior to hospitalisation. NAC infusion (100 mg/kg) was administered as soon as ALF was diagnosed, based on low GCS scores, raised transaminases and prolonged prothrombin/INR. Full clinical and biochemical recovery occurred in all patients. CONCLUSIONS A successful outcome followed early administration of NAC to children with ALF complicating severe dengue infection.

Cerebral thrombosis in beta-thalassaemia major.

Two patients with homozygous beta thalassaemia complicated by cerebral thrombosis are reported. An alteration in coagulability due to a sudden increase in haematocrit and platelets was the probable cause in one patient. Although the other patient had many complications of thalassaemia, the cause for cerebral thrombosis was not identifiable.

Ocular and subcutaneous dirofilariasis in a Sri Lankan infant: an environmental hazard caused by dogs and mosquitoes

Abstract An 11-month-old infant presented with a subcutaneous nodule in the right cheek which was found by ultrasonography to be a worm. Following treatment with di-ethylcarbamazine, a worm emerged from the left upper eyelid which was confirmed to be Dirofilaria repens. Dirofilariasis usually manifests as a single lesion and is rare in infants.

Pulmonary langerhans cell histiocytosis masquerading as tuberculosis in an infant

Abstract A 4-month-old infant presented with continued fever, unresolving bronchopneumonia and household contact with sputum-smear-positive tuberculosis (TB) and showed marginal improvement on anti-TB chemotherapy. Recurrent pneumothorax prompted the clinical diagnosis of TB to be revised. High-resolution CT scan of the chest and open lung biopsy confirmed the diagnosis of pulmonary Langerhans cell histiocytosis. Treatment with prednisolone and vinblastin resulted in settling of fever and resolution of respiratory symptoms and signs. In communities where the prevalence of TB is high, unusual presentations should prompt consideration of alternative diagnoses.

Acute appendicitis complicated by mass formation occurring simultaneously with serologically proven dengue fever: a case report.

IntroductionAcute abdomen and acute appendicitis are unusual clinical presentations that occur in dengue infection–caused illness. Lymphoid hyperplasia and mesenteric adenitis are possible explanations, although vasculitis in the pathology of dengue infection has not been reported. Authors of previous case reports have described mimicking of acute appendicitis discovered upon surgical treatment. Dengue virus has not been proven to cause acute appendicitis.Case presentationWe report a case of an 8-year-old Sinhalese boy who developed acute appendicitis during the acute phase of serologically confirmed dengue fever. Although abdominal pain, vomiting and right-sided tenderness were present at the time of admission, a diagnosis of acute appendicitis was considered only 18 hours later, when abdominal guarding and a well-defined mass in the right iliac fossa were detected clinically and ultrasonographically. Conservative management with intravenous antibiotics was successful.ConclusionIn areas where dengue is endemic, awareness of dengue viral infection as a non-surgical cause of acute abdomen, as well as its ability to mimic acute appendicitis, is important because unnecessary surgery-related morbidity can be decreased. However, delaying or missing the diagnosis of acute appendicitis can result in serious complications. This message is particularly relevant to clinicians, especially pediatricians and surgeons, who encounter large numbers of patients during dengue epidemics and run the risk of missing the diagnosis of acute appendicitis. Likewise, delaying or missing the diagnosis of dengue hemorrhagic fever can lead to dengue shock syndrome and even death. This case highlights the need for careful evaluation of each patient who presents with acute abdomen and dengue infection.

Identification of aero-allergen sensitization in children seeking treatment for bronchial asthma at a tertiary care hospital for children in Sri Lanka.

OBJECTIVES Despite a significant rise in asthma globally as well as in Sri Lanka, data regarding allergen sensitization patterns and other risk factors for asthma are not available. Therefore, we set out to determine the allergen sensitization patterns in children with asthma in Sri Lanka. METHODS Skin prick testing for common indoor aeroallergens (cockroach, cat, dog, house dust mite, moulds) were carried out in 156 children with bronchial asthma at Lady Ridgeway Hospital for Children. RESULTS 49.1% of the patients were sensitized to at least one allergen and 6.4% were sensitized to three or more allergens. Of the children 37.8% tested positive to house dust mite, 23.7% to cockroach, 5.8% to indoor moulds, 12.2% to cats and 8.9% to dogs. Allergen sensitization was significantly less in children aged four years or younger than in older children (p<0.0001). A family history of asthma or allergic rhinitis (AR) was a significant risk factor (p<0.0001) for allergen sensitization (OR 10.9, 95% CI 3.9 to 30.1). Frequency of symptoms was significantly higher in those who used firewood alone compared to those who used other fuels (OR 2.5, 95% CI 1.1 to 5.8). CONCLUSIONS Sensitization to aero-allergens was seen in a majority of children with asthma. Sensitization was significantly more in children above 4 years of age. Patients with more frequent symptoms and with AR were more likely to be sensitized to allergens.

Disseminated BCG in an infant with interleukin-12 receptor B1 (IL12RB1) deficiency

Abstract Although neonatal vaccination with bacille Calmette–Guérin (BCG) is considered to be safe, complications with disseminated disease are associated with underlying immuno-deficiency disorders. A BCG-vaccinated 4-month-old girl of Sri Lankan parentage developed progressive left axillary lymphadenopathy and severe bronchopneumonia. Lymph node biopsy demonstrated epithelioid granulomata and acid-fast bacilli. An older sibling had had a similar clinical presentation and the outcome had been fatal. Investigation for immuno-deficiency detected complete IL12RB1 deficiency. Full recovery followed a prolonged course of anti-tuberculous chemotherapy. She was put on lifelong isoniazid prophylaxis. In HIV-negative infants with unusual complications related to BCG vaccination, a primary immuno-deficiency disorder should be considered.

A child presenting with tuberculous spondylitis in a single third cervical vertebra: a case report

IntroductionDespite a global reduction in tuberculosis, extrapulmonary tuberculosis is increasing. Spinal tuberculosis remains the commonest form of skeletal tuberculosis. Cervical spine involvement is rare but is the most dangerous form because of diagnostic difficulties and serious residual disability. We report a child who had single vertebral involvement of her third cervical vertebra which is extremely rare. To the best of our knowledge isolated third cervical vertebra involvement in a child by tuberculosis has not been reported previously. Difficulties in obtaining material for histology and bacterial culture from this critical location and how the diagnosis was reached despite these challenges are highlighted.Case presentationA 10-year-old Sinhalese girl developed painful torticollis and ‘cries during sleep’. She had received Bacillus Calmette–Guérin vaccine at birth, was well nourished, and had no loss of weight, anorexia or contact with tuberculosis. A plain radiograph of her neck showed a collapsed third cervical vertebra with no disc involvement. Magnetic resonance imaging confirmed isolated destruction of third cervical vertebra associated with prevertebral soft tissue swelling indenting the thecal sac without cord compression. Her chest radiograph was normal. There was peripheral lymphocytosis, elevated erythrocyte sedimentation rate, negative tuberculin (Mantoux) test, and negative QuantiFERON®-TB GoldIn-Tube assay. Invasive procedures to obtain tissue for histology, smear or culture were perceived by parents as dangerous due to surrounding critical structures and consent was denied. The differential diagnosis included spinal tuberculosis and unifocal Langerhan cell histiocytosis. Nocturnal symptoms and the prevertebral collection of soft tissue (‘cold abscess’) were characteristic of tuberculosis, and nonspecific findings of elevated erythrocyte sedimentation rate and lymphocytosis supported this diagnosis. An incidental finding of a calcified hepatic nodule when evaluating for multifocal histiocytosis was presumed to be tuberculous because schistosomiasis and visceral leishmaniasis were extremely rare in her country of residence, Sri Lanka. Empirical treatment with a 12-month course of antitubercular therapy resulted in clinical recovery and radiological healing. There was no kyphosis or neurological sequel.ConclusionsThis report highlights to clinicians the value of a high index of suspicion and careful history taking in spinal tuberculosis; and how a combination of nonspecific findings helped reach a clinicoradiological diagnosis.