ABSTRACT
BACKGROUND: Inherited tubulopathies are a heterogeneous group of genetic disorders making whole-exome sequencing (WES) the preferred diagnostic methodology. METHODS: This was a multicenter descriptive study wherein children (< 18 years) with clinically suspected tubular disorders were recruited for molecular testing through WES. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were done when required. Variants were classified as per American College of Medical Genetics 2015 guidelines and pathogenic (P)/likely pathogenic (LP) variants were considered causative. RESULTS: There were 77 index cases (male =73%). Median age at diagnosis was 48 months (IQR 18.5 to 108 months). At recruitment, the number of children in each clinical group was as follows: distal renal tubular acidosis (dRTA) = 25; Bartter syndrome = 18; isolated hypophosphatemic rickets (HP) = 6; proximal tubular dysfunction (pTD) = 12; nephrogenic diabetes insipidus (NDI) = 6; kidney stone/nephrocalcinosis (NC) = 6; others = 4. We detected 55 (24 novel) P/LP variants, providing genetic diagnoses in 54 children (70%). The diagnostic yield of WES was highest for NDI (100%), followed by HP (83%; all X-linked HP), Bartter syndrome (78%), pTD (75%), dRTA (64%), and NC (33%). Molecular testing had a definite impact on clinical management in 24 (31%) children. This included revising clinical diagnosis among 14 children (26% of those with a confirmed genetic diagnosis and 18% of the overall cohort), detection of previously unrecognized co-morbidities among 8 children (sensorineural deafness n = 5, hemolytic anemia n = 2, and dental changes n = 1) and facilitating specific medical treatment for 7 children (primary hyperoxaluria n = 1, cystinosis n = 4, tyrosinemia n = 2). CONCLUSION: WES is a powerful tool in the diagnosis and management of children with inherited tubulopathies in the Indian population. A higher resolution version of the Graphical abstract is available as Supplementary information.
Subject(s)
Acidosis, Renal Tubular , Bartter Syndrome , Diabetes Insipidus, Nephrogenic , Nephrocalcinosis , Acidosis, Renal Tubular/diagnosis , Acidosis, Renal Tubular/genetics , Bartter Syndrome/diagnosis , Bartter Syndrome/genetics , Child , Female , Humans , India/epidemiology , Male , Exome SequencingABSTRACT
INTRODUCTION: Clinical and outcome profiles of childhood seizures can be different in resource limited settings where neurologists face lots of challenges in diagnosis and management of seizure. This study was conducted to investigate the clinical profile, causes and outcome of afebrile seizures in children in resource limited settings. METHODS: This was a prospective hospital based study. Children with afebrile seizures were followed up with exclusion of febrile and acute provoked seizures. Clinical, investigation, treatment and outcome parameters were analyzed. RESULTS: Study included 308 (age one month to 20 years) children. Median age at first seizure was 39 (inter quartile range 12-96) months. History of status epilepticus was present in 26.0%. Cause of seizure was known in 44.2%. Seizure was generalized in 79.2%, partial in 14.0% and unclassified in 6.8%. Common causes of seizure were - birth asphyxia (12.3%), neurocysticercosis (8.8%), sequel of nervous system infection (6.5%) and structural brain abnormalities (7.1%). Neurological examination, electroencephalography and computed tomography (CT) were abnormal in 24.4%, 70.5% and 27.9% cases respectively. Seizure control was achieved in 79.3% and by monotherapy in 85.0 % cases. Seizure control with single drug, seizure without recurrence and idiopathic seizure were associated with favourable outcome. CONCLUSIONS: Prevention and control of birth asphyxia, neurocysticercosis and nervous system infections are needed to reduce the burden of afebrile seizures in this area. CT is a valuable diagnostic tool and response to monotherapy is good. Seizure control with single drug, seizure without recurrence and idiopathic seizure are favourable prognostic factors.
Subject(s)
Seizures, Febrile/diagnosis , Seizures, Febrile/etiology , Adolescent , Anticonvulsants/therapeutic use , Child , Child, Preschool , Electroencephalography , Female , Humans , Infant , Male , Nepal , Prognosis , Prospective Studies , Recurrence , Risk Factors , Seizures, Febrile/therapy , Socioeconomic Factors , Tomography, X-Ray Computed , Young AdultABSTRACT
BACKGROUND: Urinary screening tests for early detection of renal diseases in asymptomatic school children and adolescents are important in the detection of silent renal diseases. OBJECTIVES: The purpose of the study was to determine the prevalence of occult renal diseases by dipstick test (reagent strips) in asymptomatic Nepalese children. PATIENTS AND METHODS: A total of 2,243 school children, aged 5-15 years, were screened for urinary abnormalities using dipstick test screening. The children who tested positive in the first screening were re-tested after 2-4 weeks. RESULTS: In the first screening, 123 children (5.5%) tested positive for isolated hematuria and proteinuria and for combined hematuria and proteinuria. Of these children, 16 (0.71%) cases tested positive in a second screening. Subsequently, 1 child from the secondary screening group was lost to follow up, 5 tested normal and 10 revealed abnormalities. Glomerulonephritis was the most commonly detected disorder (50%). CONCLUSIONS: Urinary screening was found to be useful in identifying occult renal diseases in asymptomatic children. Urinary screening would therefore not only help in early detection but also in the prevention of the deterioration of renal function later in life.