Management strategies for common viral infections in pediatric renal transplant recipients.

Viral infections have been considered as a major cause of morbidity and mortality after kidney transplantation in pediatric cohort. Children are at high risk of acquiring virus-related complications due to immunological immaturity and the enhanced alloreactivity risk that led to maintenance of high immunosuppressive regimes. Hence, prevention, early detection, and prompt treatment of such infe ctions are of paramount importance. Among all viral infections, herpes viruses (herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus), hepatitis B and C viruses, BK polyomavirus, and respiratory viruses (respiratory syncytial virus, parainfluenza virus, influenza virus and adenovirus) are common in kidney transplant recipients. These viruses can cause systemic disease or allograft dysfunction affecting the clinical outcome. Recent advances in tech nology and antiviral therapy have improved management strategies in screening, monitoring, adoption of prophylactic or preemptive therapy and precise trea tment in the immunocompromised host, with significant impact on the outcome. This review discusses the etiology, screening and monitoring, diagnosis, pre vention, and treatment of common viral infections in pediatric renal transplant recipients.

Expanding the phenotype of DYNC1H1-associated diseases with a rare variant resulting in spinal muscular atrophy with lower extremity predominance (SMA-LED) and upper motor neuron signs.

BACKGROUND: Spinal muscular atrophy with lower extremity predominance (SMA-LED) is an autosomal dominant disorder. Since SMA-LED affects lower motor neurons, the disease is characterized by weakness and atrophy of lower limb muscles. We present a familial case series of SMA-LED with upper motor neuron signs associated with a rare variant in DYNC1H1. CASE: The index case was referred to Pediatric Neurology at the age of two and half years, due to delayed mobility. The child was diagnosed with congenital vertical talus at birth, which was managed with serial bilateral casting and surgery. The delayed mobility was initially attributed to lower limb weakness secondary to prolonged periods of immobilization from casting of his lower limbs. He had a striking waddling gait and proximal muscle weakness on neurological assessment. He had lower motor neuron signs predominantly in his lower limbs that were in keeping with SMA-LED. Surprisingly, he also demonstrated a brisk crossed adductor response that was not in keeping with an isolated primary neuro-muscular disorder and suggested a mixed upper and lower motor neuron pathology. The inherited neuropathy gene panel revealed a heterozygous sequence change in the DYNC1H1 gene which was present in all affected family members. CONCLUSIONS: We present the first report of a familial case series of SMA-LED with upper motor neuron signs associated with an extremely rare variant in DYNC1H1: c.1808A > T (p.Glu603Val). As per the American College of Medical Genetics and Genomics (ACMG) guidelines for variant classification, we would recommend that this variant be reclassified as `Likely Pathogenic` due to matching 1 moderate (PM1-PM6) and ≥4 supporting (PP1-PP5) criteria in the reported case series.

Fifteen-minute update: International normalised ratio as the treatment end point in children with acute paracetamol poisoning.

Paracetamol is one of the most frequent reasons for poisonings across the UK with an estimated 90,000 patients and 150 deaths annually. International normalised ratio (INR) may be elevated due to hepatocellular damage and is frequently used to monitor progress on N-acetyl cysteine. N-acetyl cysteine is associated with reduced activity of vitamin K dependent clotting factors leading to a benign elevation of INR. In asymptomatic children with normal aspartate transaminase/alanine transaminase, isolated borderline elevation of INR following paracetamol overdose should be reviewed for possible N-acetyl cysteine induced elevation of INR. Due to these factors, in those with borderline persistent elevation of INR, N-acetyl cysteine can be safety stopped if INR is falling on two or more consecutive tests and is <3.0.

Arthrogryposis multiplex congenita in a child with congenital fractures: a case report.

BACKGROUND: Bruck syndrome is an exceedingly rare form of osteogenesis imperfecta, inherited autosomal recessively and presenting with the concurrence of bone fragility and congenital contractures of large joints. The disease usually progresses relentlessly to result in recurrent fractures, short stature, severe kyphoscoliosis, and susceptibility to recurrent respiratory tract infections. CASE PRESENTATION: The index child was a male newborn to healthy, nonconsanguineous, Sinhalese parents. The child had multiple contractures involving all large joints with pterigium formation in addition to congenital fractures involving left humerus and ulna at birth. The phenotypic features in this child were highly suggestive of Bruck syndrome. Genetic counseling was offered to the parents, although specific genetic testing could not be undertaken due to lack of resources. Bone and skin biopsy were not performed since only palliative care was possible. Over the course, he developed recurrent severe chest infections due to poor muscle tone, weak cough reflex, and pooling of secretions. Unfortunately, he succumbed at the age of 7 months following severe pneumonia. CONCLUSION: The association of arthrogryposis with osteogenesis imperfecta is extremely rare and known as Bruck syndrome. Early diagnosis during the antenatal period is helpful in genetic counseling, assessment of severity, and exploration of therapeutic options.

Postdengue chronic fatigue syndrome in an adolescent boy.

Chronic fatigue syndrome (CFS) is often preceded by a viral illness and has recurrent 'flulike' symptoms which include a wide spectrum of musculoskeletal and neurological clinical features. The condition is also known as myalgic encephalomyelitis and systemic exertional intolerance syndrome. CFS has been reported following dengue among adult patients. We report the case of an 11-year-old boy who developed CFS following recovery of dengue haemorrhagic fever (DHF). The reported child was initially managed as for DHF and was clinically asymptomatic on post-discharge day 3. He was re-admitted after 3 weeks with severe joint pains, myalgia and unbearable headache. As his symptoms persisted, he was investigated in-depth. All investigations were normal except mild elevation of liver functions. The diagnosis of CFS secondary to DHF was made by exclusion of differential diagnosis. At 1-year follow-up, patient continues to have symptoms after treatment with physiotherapy and nutrition counselling.

PHACE Syndrome Presenting With Retinal Degeneration, Cortical Dysplasia, Microphthalmia, and Atrial Septal Defect in a South Asian Boy.

PHACE syndrome is a rare disorder of vasculogenesis that occurs during the first trimester of pregnancy. The disorder commonly presents with posterior fossa brain anomalies and coarctation of aorta/arterial anomalies and is predominantly seen in female patients. Herein, we report a male child with PHACE syndrome who had several less common features such as cortical dysplasia, retinal degeneration, and microphthalmia. The diagnosis of PHACE syndrome was confirmed based on revised diagnostic criteria and by the presence of one major criterion and two minor criteria in addition to >5 cm haemangioma. Further, the reported child had atrial septal defect as the only cardiac abnormality, and this has been rarely described in patients with PHACE syndrome.

Multiple aplasia cutis congenita type V and fetus papyraceous: a case report and review of the literature.

BACKGROUND: Aplasia cutis congenita is regarded as congenital focal absence of skin in the newborn, and occurrence of more than three similar skin defects is rare. The etiology is thought to be multifactorial, and precise etiopathogenesis is unknown. CASE PRESENTATION: A 13-day-old newborn Sri Lankan Tamil girl was referred to the dermatologic clinic with multiple skin defects at birth. There were six lesions on the body, and two of them had healed during intrauterine period, leaving scars. This was a second twin of her pregnancy. Her first twin fetus had demised before 19 weeks of pregnancy and was confirmed to be fetus papyraceous based on ultrasound-guided fetal assessment. The said child was thoroughly investigated and found to have no other congenital abnormalities. Chromosomal studies yielded normal findings. She was treated with tropical antibacterial ointment, and all lesions resolved spontaneously within 4 weeks, leaving scars. Physiotherapy was commenced to prevent contracture formation, and follow-up was arranged in collaboration with the plastic surgical team. CONCLUSIONS: Aplasia cutis congenita is a rare condition of uncertain etiology, but consanguinity may play a role. This report described a newborn with type V cutis aplasia congenita in whom the diagnosis was confirmed based on clinical features and revision of antenatal history. The management depends on the pattern, extent, location, severity, underlying causes, and associated anomalies.

Exome sequencing detected an extremely rare case of foetal onset familial haemophagocytic lymphohistiocytosis type 5 presenting with hydrops foetalis.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous autosomal recessive hyper-inflammatory syndrome which needs early accurate diagnosis and appropriate treatment to prevent complications and early mortality. Recently, it was reported that mutations in STXBP2 gene are linked to FHL type 5 (FHL-5). CASE PRESENTATION: We report a Sri Lankan neonate who presented with low Apgar scores at birth, abdominal distension, and hepatosplenomegaly, followed by lethargy, poor sucking and rapid decompensation with wide spread activation of inflammation within 48 h of birth. Her elder sibling also had a similar presentation during early neonatal period and deceased at two weeks of age with no diagnosis. Unfortunately, the index case deceased at 14 days of age following multi-organ dysfunction and severe metabolic acidosis. Targeted gene panel followed by reflex exome sequencing revealed a novel likely pathogenic homozygous variant in the STXBP2 gene (NM_001272034.1:c.1141-2A > G) which confirmed the diagnosis of autosomal recessive FHL-5. CONCLUSION: Early diagnosis of FHL type 5 using genetic analysis and timely treatment are difficult in the absence of family history due to a wide spectrum of clinical manifestations. However both early diagnosis and treatment doesn't alter the long term prognosis. So genetic counselling would be the better option.

Homozygous autosomal recessive hypercholesterolaemia in a South Asian child presenting with multiple cutaneous xanthomata.

Autosomal recessive hypercholesterolemia (ARH; OMIM #603813) is an extremely rare disorder of lipid metabolism caused by loss-of-function variants in the LDL receptor adapter protein 1 (LDLRAP1) gene, which is characterized by severe hypercholesterolaemia and an increased risk of premature atherosclerotic cardiovascular disease. We report the case of an 11-year-old girl who presented with multiple painless yellowish papules around her elbows and knees of two-year duration. She had been reviewed by several general practitioners, with some of the papules having been excised, but without a specific diagnosis being made. The child was referred to a paediatric service for further evaluation and treatment of the cutaneous lesions, which appeared xanthomatous in nature. A lipid profile showed severe hypercholesterolaemia. Next generation sequencing analysis of a monogenic hypercholesterolaemia gene panel revealed homozygosity for a pathogenic frameshift mutation, c.71dupG, p.Gly25Argfs*9 in LDLRAP1. Her parents and brother, who were asymptomatic, were screened and found to be heterozygous carriers of the LDLRAP1 variant. There was no known consanguinity in the family. She was commenced on the HMG-CoA reductase inhibitor, atorvastatin, to good effect, with a ∼76% reduction in LDL-cholesterol at a dose of 50 mg per day. At six-month follow-up, there had been no obvious regression of the xanthomata, but importantly, no enlargement of, or the development of new papular lesions, have occurred. In summary, we report a child who presented with multiple cutaneous xanthomata and was confirmed to have ARH by the presence of a homozygous novel pathogenic frameshift variant in LDLRAP1.

Clinical and Radiological Characterization of an Infant with Caudal Regression Syndrome Type III.

Caudal regression syndrome is a rare disorder of developmental failure of lumbosacral vertebra and corresponding spinal cord during notochord formation. The severity varies from absent coccyx to complete absence of lumbosacral vertebra and caudal spinal cord. Both genetic and environmental factors are believed to play roles in aetiopathogenesis of caudal regression. The authors report a two-month-old child born to a diabetic mother, in whom the diagnosis of caudal regression syndrome type III was confirmed based on clinical and radiological characteristics. The child was managed by the multidisciplinary team to continue supportive care and screen and monitor for long-term complications. The long-term prognosis for mobility was less favourable given the presence of bilateral hip dysplasia and involvement of lumbar vertebra in addition to sacral agenesis.

Focal Status and Sub-Ependymal Tumor as Features of the First Presentation in a Child With Tuberous Sclerosis.

Tuberous sclerosis (TS) is an autosomal dominant inherited disorder that affects multiple organ systems. Usually, children with TS present either with neurocutaneous stigmata or seizures during the early years of life. The mortality and morbidity are related to refractory epilepsy, giant cell astrocytoma and related complications, and multiple angiomyolipomas. The authors have reported an eleven-year-old child in whom focal status and sub-ependymal tumor were the features of the first presentation of tuberous sclerosis. The report further highlights the importance of early identification of cutaneous features by primary care providers and parents to enable early comprehensive multi-disciplinary management.

GTP-Cyclohydrolase I deficiency presenting as malignant hyperphenylalaninemia, recurrent hyperthermia and progressive neurological dysfunction in a South Asian child - a case report.

BACKGROUND: Tetrahydrobiopterin (BH4) deficiencies are disorders affecting phenylalanine homeostasis, and catecholamine and serotonin biosynthesis. GTP-Cyclohydrolase I deficiency (OMIM 600225) is an extremely rare variant of inborn error of BH4 synthesis which exists in recessive and dominant forms. The recessive form presents with complex neurological and autonomic dysfunction whilst the dominant form presents as Dopa-responsive dystonia. CASE PRESENTATION: We describe a South Asian child who initially presented with neurological dysfunction and recurrent vomiting and later developed recurrent hyperthermia for several months. The child did not have screening for hyperphenylalaninemia at birth and was found to have marked hyperphenylalaninemia after clinical presentation at 5 months. Further evaluation revealed BH4 deficiency. GTP-Cyclohydrolase I deficiency (GTPCH) was identified based on normal dihydro pteridine reductase activity and markedly reduced neopterin in dried blood spot test. After institution of treatment and control of high phenylalanine levels, clinical deterioration decelerated yet with noticeable residual neurological dysfunction. CONCLUSION: To authors' knowledge, this is first report of GTPCH deficiency in a South Asian child. The case highlights practical issues regarding diagnosis of GTPCH deficiency, especially in countries without broader universal newborn screening programs for early detection of inherited metabolic disorders. Testing for GTPCH deficiency should be considered for patients with unexplained neurological and autonomic symptoms following initial metabolic screen.

Patterns of acute poisoning with pesticides in the paediatric age group.

BACKGROUND: Pesticides are identified as one of the dangerous poisons globally in children and are associated with increased short- and long-term morbidity. Pesticide poisoning is the most common method of self-poisoning among adults in rural Sri Lanka, and the clinical management is associated with significant healthcare costs to the country. There is however little data published on acute pesticide poisoning among children in rural Sri Lanka. The current study aimed to comprehensively evaluate clinical profiles, harmful first aid measures, emergency clinical management, complications and outcomes related to acute pesticide poisoning among children in the rural community of Sri Lanka. METHODS: This multicenter study was conducted in the North Central Province of Sri Lanka involving all children with acute pesticide poisoning and who were between 9 months and 12 years of age. Data were collected over 7 years (2007-2014), and children from 36 hospitals were recruited. Data collection was carried out by pretested, multi-structured, interviewer-administered questionnaires to identify clinical profiles of children, harmful first aid measures, emergency clinical management, reasons for delayed management, complications and outcomes of pesticide poisoning events. RESULTS: Among 1621 children with acute poisoning, 9.5% (155) comprised children with acute pesticide poisoning. Male children outnumbered female children, and the majority of children were less than 5 years. Most common pesticides implicated in poisoning of children were organophosphates and carbamates. Gastrointestinal and neurological symptoms were predominant clinical features. Limited transport and lack of concern regarding urgency among caregivers were leading reasons for delayed management. Most common location for poisoning was cultivation lands. Harmful first aid measures were practiced in 32.4%. 7.1% had intentional pesticide poisoning. The case fatality rate of all pesticide poisonings in the study was 1.9%. 58.1% of patients were transferred between regional hospitals and teaching hospital. Cardiac and respiratory arrests, aspiration pneumonia and convulsions were among the reported complications. CONCLUSIONS: Acute pesticide poisoning in paediatric age group (<12 years) is a relatively uncommon yet significant cause of child health-related morbidity and mortality in rural Sri Lanka. Patterns of poisoning represent the pattern of pesticide use by the rural community. The practice of harmful first aid measures by caregivers and delay in attending the emergency department may negatively impact patient outcomes.