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Clinical and biochemical profile of children with short stature presenting to a tertiary care centre: a 3 years prospective observational study

Author: 
Pratiksha Singh, Divij Pasrija, Sunil Polipalli, Sumaira Khalil and Seema Kapoor
Subject Area: 
Health Sciences
Abstract: 

Objective: To evaluate the clinical and biochemical profile and Growth hormone receptor Polymorphism of children presenting with short stature to a tertiary care centre, and also to study the molecular players/polymorphism that might give us an insight into good response to a relatively expensive modality of treatment. This would thus be directing resources to patients with GH deficiency who would respond best to it. Materials and Methods: This was an observational study on short stature children presenting to a tertiary care hospital over a period of 3 years. Short stature was defined as height or length less than -2 SD of age and sex matched population using reference WHO growth charts and or growth velocity lower than the 25th percentile for age for at least 1 year or lower than the 10th percentile for age for at least 6 months. All children enrolled underwent extensive baseline work up to investigate for causes of short stature like Endocrine causes (Hypothyroidism, Laron’s syndrome), malnutrition, chronic diseases (Thalassemia, chronic kidney disease and renal tubular acidosis), celiac disease, syndromic association, Skeletal dysplasia, Familial short stature, Constitutional short stature and Idiopathic short stature. In children with pathological short stature in whom an identifiable cause of short stature was not found on routine investigations, serum growth hormone (GH), IGF-1 and IGFBP-3 levels were estimated using 2 different pharmacological stimuli.GH value of less than 10 mg/L were considered to be GH deficient. Children with Growth Hormone Deficiency (GHD) were subjected to analysis of the GHD3 exon deletion status. For the genotyping of GHR exon 3 locus, the frequency of GHR transcript variants with retention (GHRfl) or exclusion (GHRd3) of exon 3 was tested by the multiplex PCR assay. This was performed with primers G1, G2, and G3 with a well defined protocol. Result: A total of 473 children with a median age of 3.65 years (Range 2-18 years) were enrolled. Twenty three percent of the children each were diagnosed as Growth hormone deficient and Idiopathic short stature. Celiac disease also contributed significantly in 18% of cases. The other causes seen were skeletal dysplasia (7%), syndromic (12%) and malnutrition (2%). Amongst children with endocrine disorders, 40% children had hypothyroidism, panhypopituitarism was seen in 10% children and 50% had Laron’s syndrome. In Children with chronic disorders, 72% were diagnosed with Thalassemia, 21% with chronic kidney disease and 1 child had renal tubular acidosis. Constitutional and familial short stature were seen in 6% and 2% children respectively. Amongst patients with GHD, 60.7% had wild type (GHRfl/fl), 19.2% were heterozygous (GHRfl/GHRd3) and 20.1% were homozygous (GHRd3/d3), whereas for idiopathic short stature they were 67.5%, 14.5% and 18% respectively. Conclusion: With high index of suspicion, availability of testing and following an algorithmic approach, diagnosis could be attained in 85% of cases. Our data indicates the changes in profile from those reported earlier in our country. Growth hormone deficiency and celiac disease contribute significantly even though majority are normal variants. Also, genotyping done would help in prediction of response to recombinant GH therapy in a resource constraint resulting in appropriation of finances which could be utilized for a higher priority area.

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