Two novel mutations with 17 hydroxylase deficiency – Alpha and beta presenting as 46XY disorders of sexual development

17 alpha-hydroxylase and 17 beta-hydroxylase deficiency are rare causes of 46XY disorders of sexual development. The gene for 17 alpha-hydroxylase enzyme (CYP17A1) is located at 10q24.3 and for 17 beta-hydroxylase is (17βHSD3) on 9q22. CYP17A1 can present with delayed puberty and hyporeninemic, hypokalemic hypertension. In 17βHSD3 deficiency, a biochemical pointer to diagnosis includes a stimulated ratio of testosterone (T) to androstenedione (A) of <0.8. We report two cases, one with 17βHSD3 defect in infancy with atypical genitalia and second with CYP17A1 which presented in childhood with novel mutations. There is a wide spectrum of phenotypic presentations of these disorders. Genetic analysis gives confirmation

Catch-Up Growth in Infants and Young Children With Faltering Growth:Expert Opinion to Guide General Clinicians

Faltering growth (FG) is a problem regularly seen by clinicians in infants and young children (&lt;2 years of age). It can occur due to non-disease-related and disease-related causes and is associated with a wide range of adverse outcomes, including shorter-term effects such as impaired immune responses and increased length of hospital stay, and longer-term consequences, including an impact on schooling and cognitive achievements, short stature, and socioeconomic outcomes. It is essential to detect FG, address underlying causes and support catch-up growth where this is indicated. However, anecdotal reports suggest misplaced fear of promoting accelerated (too rapid) growth may deter some clinicians from adequately addressing FG. An invited international group of experts in pediatric nutrition and growth reviewed the available evidence and guidelines on FG resulting from disease-related and non-disease-related effects on nutritional status in healthy term and small for gestational age infants and children up to the age of 2 years in low-, middle-, and high-income countries. Using a modified Delphi process, we developed practical consensus recommendations to provide clarity and practical recommendations for general clinicians on how FG should be defined in different young child populations at risk, how FG should be assessed and managed, and the role of catch-up growth after a period of FG. We also suggested areas where further research is needed to answer remaining questions on this important issue.</p

Catch-up Growth in Infants and Young Children with Faltering Growth: Expert Opinion to Guide General Clinicians

Faltering growth (FG) is a problem regularly seen by clinicians in infants and young children (<2 years of age). It can occur due to non-disease related and disease-related causes and is associated with a wide range of adverse outcomes, including shorter-term effects such as impaired immune responses and increased length of hospital stay, and longer-term consequences, including an impact on schooling and cognitive achievements, short stature, and socioeconomic outcomes. It is essential to detect FG, address underlying causes and support catch-up growth where this is indicated. However, anecdotal reports suggest misplaced fear of promoting accelerated (too rapid) growth may deter some clinicians from adequately addressing faltering growth. An invited international group of experts in paediatric nutrition and growth reviewed the available evidence and guidelines on FG resulting from disease-related and non-disease-related effects on nutritional status in healthy term and small for gestational age (SGA) infants and children up to the age of two years in low-, middle- and high-income countries. Using a modified Delphi process, we developed practical consensus recommendations to provide clarity and practical recommendations for general clinicians on how faltering growth should be defined in different young child populations at risk, how faltering growth should be assessed and managed and the role of catch-up growth after a period of faltering growth. We also suggested areas where further research is needed to answer remaining questions on this important issue

Catch-Up Growth in Infants and Young Children With Faltering Growth: Expert Opinion to Guide General Clinicians.

Faltering growth (FG) is a problem regularly seen by clinicians in infants and young children (<2 years of age). It can occur due to non-disease-related and disease-related causes and is associated with a wide range of adverse outcomes, including shorter-term effects such as impaired immune responses and increased length of hospital stay, and longer-term consequences, including an impact on schooling and cognitive achievements, short stature, and socioeconomic outcomes. It is essential to detect FG, address underlying causes and support catch-up growth where this is indicated. However, anecdotal reports suggest misplaced fear of promoting accelerated (too rapid) growth may deter some clinicians from adequately addressing FG. An invited international group of experts in pediatric nutrition and growth reviewed the available evidence and guidelines on FG resulting from disease-related and non-disease-related effects on nutritional status in healthy term and small for gestational age infants and children up to the age of 2 years in low-, middle-, and high-income countries. Using a modified Delphi process, we developed practical consensus recommendations to provide clarity and practical recommendations for general clinicians on how FG should be defined in different young child populations at risk, how FG should be assessed and managed, and the role of catch-up growth after a period of FG. We also suggested areas where further research is needed to answer remaining questions on this important issue

Invited commentary to the paper ‘Zinc status and its association with the health of adolescents: a review of studies in India’

We are pleased to view the article based on Dr. Rama Kawade's thesis illustrating the importance of micronutrient adequacy, especially zinc, and associated health implications in Indian adolescent girls. This brief commentary addresses three major aspects in which Kawade's work has made a significant contribution; nutrition and health issues of adolescents, rising importance of zinc in terms of deficiency problems being addressed, and development of dietary interventions to alleviate micronutrient deficiencies

International Consensus Guideline on Small for Gestational Age (SGA): Etiology and Management from Infancy to Early Adulthood

: This International Consensus Guideline was developed by experts in the field of SGA of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Besides, it presents long-term consequences of SGA birth and new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, and the metabolic and cardiovascular health of young adults born SGA after cessation of childhood-GH-treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardio-metabolic health profile in adulthood. Children born SGA with persistent short stature &lt; -2.5 SDS at age 2 years or &lt; -2 SDS at age of 3-4 years, should be referred for diagnostic work-up. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033-0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3-4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle

Disorders of sex development : insights from targeted gene sequencing of a large international patient cohort

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. Results: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46, XY DSD and 48 with 46, XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46, XY DSD. In patients with 46, XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. Conclusions: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes

Growth charts: A diagnostic tool

Context: Assessment of growth by objective anthropometric methods is crucial in child care. India is in a phase of nutrition transition and thus it is vital to update growth references regularly. Objective: To review growth standards and references for assessment of physical growth of Indian children for clinical use and research purposes. Materials and Methods: Basics of growth charts and importance of anthropometric measurements are described. A comparison between growth standards and references is provided. Further, Indian growth reference curves based on the data collected by Agarwal et al. and adopted by the Indian Academy of Pediatrics, World Health Organization growth standards for children under the age of 5 years (2006) and contemporary Indian growth references published on apparently healthy affluent Indian children (data collected in 2007-08) are discussed. The article also discusses the use of adult equivalent body mass index (BMI) cut-offs for screening for overweight and obesity in Indian children. Results and Conclusions: For the assessment of height, weight and BMI, WHO growth standards (for children < 5 years) and contemporary cross sectional reference percentile curves (for children from 5-18 years) are available for clinical use and for research purposes. BMI percentiles (adjusted for the Asian adult BMI equivalent cut-offs) for the assessment of physical growth of present day Indian children are also available. LMS values and Microsoft excel macro for calculating SD scores can be obtained from the author (email: [email protected]). Contemporary growth charts can be obtained by sending a message to 08861201183 or email: [email protected]