ABSTRACT
Mucopolysaccharidosis [MPS] are classified into seven clinical types based on eleven known lysosomal enzyme deficiencies of glycosaminoglycan [GAG] metabolism. Respiratory involvement seen in most MPS types includes recurrent respiratory infections, upper and lower airway obstruction, tracheomalacia, restrictive lung disease, and sleep disturbances. To delineate the pattern of respiratory compromise and pulmonary function abnormalities in MPS patients. This is a cross section observational study conducted on 30 patients recruited from the Neurometabolic Clinic, Children's Hospital, Cairo University over a period of 18 months. All patients were screened first by the quantitative determination of GAGs in urine, and diagnosis was confirmed by unidimensional electrophoresis for GAGs in urine and/or specific enzymatic assay in blood leucocytes. Infant pulmonary functions [IPFT] were done in twenty-two patients [< 3 years of age], while 8 cases performed impulse oscillometry [IOS] test [3-6 years of age]. Ages at diagnosis ranged from 1 to 9 years with a median of 2.3 years. Male to female ratio was 4:1. Consanguinity was observed in 53.3% whereas similar family condition was present in 40% of cases. Lumbar kyphosis was detected in 60% of cases, while scoliosis was detected in 46.7%. Results of pulmonary functions were mainly obstructive in 20 [66.6%] cases; however, combined obstructive and restrictive were detected in only 6 [20%] of cases. Data showed no association between the presence of scoliosis or the presence of organomegaly and the pattern of pulmonary function abnormalities. Evaluation and follow up of patients with MPS using pulmonary function tests are essential to detect early involvement of respiratory system and hence start treatment for respiratory complications early in the course of the disease
Subject(s)
Humans , Male , Female , Respiratory Function Tests/methods , Child , Glycosaminoglycans/urineABSTRACT
A disintegrin and metalloproteinase-encoding gene [ADAM33], was recently identified as an asthma susceptibility gene. ADAM33 protein is expressed in smooth muscle cells of bronchi and pulmonary fibroblasts, playing a major role in airway remodeling. Earlier studies, have mostly confirmed a link between ADAM33 and asthma as well as bronchial hyperresponsiveness. This work studied a group of Egyptian asthmatic children for 3 ADAM33 single nucleotide polymorphisms [SNPs], previously identified as putative risk alleles: T1 G > A[rs2280091], T2 A > G[rs2280090], V4 G > C[rs2787094] using Polymerase Chain Reaction - restriction fragment length polymorphism [PCRRFLP] with emphasis on their relation to clinical [severity, smoking, family history, and atopic manifestations] and laboratory data [Ig Immunoglobulin E [Ig E] level and absolute eosinophilia] and pulmonary functions. Sixty [3-12 years old] asthmatic children and 32 matched controls were recruited. The genotype distribution for the SNPs showed no significant difference between the patients and the controls. A higher frequency of the [AA] genotype of T1 polymorphism was found in controls [75%] than in patients [41%], while the [AG] variant was higher in cases [46.6%] than in controls [21.9%] but with no statistically significant difference. Also the [GG] genotype was higher in cases [11.6%] than in controls [3.1%] but with no statistical significance. The allelic frequencies of T1 showed a higher [A] allele in controls [85.93%] than cases [65%] and higher [G] allele in cases [35%] than controls [14.06%], showing a high significant difference. No correlation was found between [T1, T2, and V4] and the demographic, clinical and laboratory parameters, except SNP T1 showing a positive correlation with Ig E level, and SNP V4 showing a positive correlation with passive smoking as a precipitating factor and borderline significance with absolute eosinophilia. In conclusion, no significant association was detected between these SNPs and asthma susceptibility in this study