BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. OBJECTIVE: Our objective was to assess the effect of mycobacterial disease in patients with CGD. METHODS: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. RESULTS: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. CONCLUSION: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.
Granulomatous Disease, Chronic/complications , Mycobacterium Infections/diagnosis , Mycobacterium Infections/etiology , BCG Vaccine/administration & dosage , Bacterial Infections/diagnosis , Bacterial Infections/epidemiology , Bacterial Infections/etiology , Bacterial Infections/mortality , Child , Child, Preschool , Female , Granulomatous Disease, Chronic/epidemiology , Granulomatous Disease, Chronic/mortality , Granulomatous Disease, Chronic/therapy , Humans , Infant , Male , Mycobacterium Infections/epidemiology , Mycobacterium Infections/mortality , Mycoses/diagnosis , Mycoses/epidemiology , Mycoses/etiology , Mycoses/mortality , Patient Outcome Assessment , Retrospective Studies , Tuberculosis/diagnosis , Tuberculosis/etiology
BACKGROUND: Nerve growth factor ß (NGFß) and tyrosine kinase receptor type A (TRKA) are a well studied neurotrophin/receptor duo involved in neuronal survival and differentiation. The only previously reported hereditary sensory neuropathy caused by an NGF mutation, c.661C>T (HSAN5), and the pathology caused by biallelic mutations in the TRKA gene (NTRK1) (HSAN4), share only some clinical features. A consanguineous Arab family, where five of the six children were completely unable to perceive pain, were mentally retarded, did not sweat, could not discriminate temperature, and had a chronic immunodeficiency, is reported here. The condition is linked to a new homozygous mutation in the NGF gene, c.[680C>A]+[681_682delGG]. METHODS: Genetic linkage and standard sequencing techniques were used to identify the causative gene. Using wild-type or mutant over-expression constructs transfected into PC12 and COS-7 cells, the cellular and molecular consequences of the mutations were investigated. RESULTS: The mutant gene produced a precursor protein V232fs that was unable to differentiate PC12 cells. V232fs was not secreted from cells as mature NGFß. CONCLUSIONS: Both the clinical and cellular data suggest that the c.[680C>A]+[681_682delGG] NGF mutation is a functional null. The HSAN5 phenotype is extended to encompass HSAN4-like characteristics. It is concluded that the HSAN4 and HSAN5 phenotypes are parts of a phenotypic spectrum caused by changes in the NGF/TRKA signalling pathway.
Hereditary Sensory and Autonomic Neuropathies/genetics , Hereditary Sensory and Autonomic Neuropathies/pathology , Nerve Growth Factor/genetics , Animals , Base Sequence , Blotting, Western , COS Cells , Chlorocebus aethiops , Chromosome Mapping , Enzyme-Linked Immunosorbent Assay , Genotype , Humans , Molecular Sequence Data , Mutation/genetics , PC12 Cells , Pedigree , Rats , Receptor Protein-Tyrosine Kinases/genetics , Receptor, trkA/genetics , Sequence Analysis, DNA
OBJECTIVE: This study aimed to determine the clinical, electroencephalographic, and radiological factors associated with medically intractable seizures in children in the Al Ain Medical District in the United Arab Emirates. METHODS: This work used a prospective case-control study of children referred to pediatric neurology and neurodevelopmental clinics at Tawam and Al Ain University Hospitals. RESULTS: There were 55 children with intractable epilepsy; their data were compared with 50 children who responded well to antiepileptic drugs and who were seizure-free for at least 2 years. Onset <1 year of age, a high seizure frequency at onset, positive history of neonatal seizures, developmental delay and status epilepticus, neurological deficits, and abnormal brain imaging results were found to be significantly more common in the study group. Symptomatic localization-related epilepsy was more common in children in this group than in the control group. CONCLUSION: Our study suggests that children who present with idiopathic localization-related and generalized epilepsy syndromes with few seizures at onset and with no neurological deficits tend to have a relatively good prognosis.
Epilepsy/diagnosis , Epilepsy/physiopathology , Adolescent , Age of Onset , Brain/physiopathology , Catchment Area, Health , Child , Child, Preschool , Demography , Electroencephalography , Epilepsy/epidemiology , Female , Humans , Infant , Male , Predictive Value of Tests , Prospective Studies , Severity of Illness Index , United Arab Emirates/epidemiology
