Hypoglycemia Due to Acquired Carnitine Deficiency in a Pediatric Patient Receiving Chemotherapy.

We describe a 21-month-old male with relapsed clear cell sarcoma of the kidney receiving enteral nutrition who experienced recurrent, ketotic hypoglycemia. During relapse therapy, he had recurrent hypoglycemia episodes, in the setting of hematochezia and diarrhea. Evaluation revealed low carnitine levels. He received supplementation with oral levocarnitine throughout the remainder of treatment, resulting in normalization of serum carnitine levels and no further hypoglycemia. We believe adverse effects of the chemotherapy on his single kidney and gastrointestinal insult resulted in hypoglycemia and carnitine deficiency. Our case highlights that carnitine deficiency should be considered when acute onset hypoglycemia without obvious cause occurs.

QRICH1 mutations cause a chondrodysplasia with developmental delay.

In many children with short stature, the etiology of the decreased linear growth remains unknown. We sought to identify the underlying genetic etiology in a patient with short stature, irregular growth plates of the proximal phalanges, developmental delay, and mildly dysmorphic facial features. Exome sequencing identified a de novo, heterozygous, nonsense mutation (c.1606C>T:p.R536X) in QRICH1. In vitro studies confirmed that the mutation impaired expression of the QRICH1 protein. SiRNA-mediated knockdown of Qrich1 in primary mouse epiphyseal chondrocytes caused downregulation of gene expression associated with hypertrophic differentiation. We then identified an unrelated individual with another heterozygous de novo nonsense mutation in QRICH1 who had a similar phenotype. A recently published study identified QRICH1 mutations in three patients with developmental delay, one of whom had short stature. Our findings indicate that QRICH1 mutations cause not only developmental delay but also a chondrodysplasia characterized by diminished linear growth and abnormal growth plate morphology due to impaired growth plate chondrocyte hypertrophic differentiation.

Disorders of Puberty: An Approach to Diagnosis and Management.

Disorders of puberty can profoundly impact physical and psychosocial well-being. Precocious puberty is pubertal onset before eight years of age in girls and before nine years of age in boys. Patients with early isolated pubertal changes, prepubertal linear growth, and no worrisome neurologic symptoms typically have a benign pattern of development and should be monitored in the appropriate clinical context. Among patients with true precocious puberty, or full activation of the hypothalamic-pituitary-gonadal axis, most girls have an idiopathic etiology, whereas it is commonly due to identifiable pathology on imaging in boys. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); thyroid function testing; and bone age radiography. Brain magnetic resonance imaging should be performed in girls younger than six years, all boys with precocious puberty, and children with neurologic symptoms. Delayed puberty is the absence of breast development in girls by 13 years of age and absence of testicular growth to at least 4 mL in volume or 2.5 cm in length in boys by 14 years of age. Constitutional delay of growth and puberty is a common cause of delayed puberty; however, functional or persistent hypogonadism should be excluded. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); and bone age radiography. Abnormal growth velocity necessitates assessment of serum thyroid function, prolactin, and insulinlike growth factor I. Boys 14 years and older and girls 13 years and older may benefit from sex steroid treatment to jump-start puberty. Referral to a pediatric endocrinologist may be warranted after the initial evaluation.

A Case of Mayer-Rokitansky-Küster-Hauser Syndrome Diagnosed in Infancy after Evaluation of Palpable Gonads.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is defined as incomplete development of Müllerian structures (uterus, fallopian tubes, proximal vagina) in an otherwise phenotypic female individual. MRKH syndrome typically presents in adolescence with primary amenorrhea, but has been diagnosed in younger patients who present with other associated abnormalities, most commonly renal and skeletal. CASE: Here we describe a 46,XX female infant with prenatally diagnosed renal anomalies who was found to have bilateral inguinal ovarian hernias at 1 month of age. Imaging of the genitourinary system revealed absence of the uterus and proximal vagina, consistent with MRKH syndrome. SUMMARY AND CONCLUSIONS: This case highlights the importance of a thorough physical examination and an interdisciplinary team evaluation of infants with genitourinary anomalies, particularly when there is concern for differences in sexual development.

Talking About Childhood Obesity: A Survey of What Parents Want.

OBJECTIVE: Determine parent preferences when discussing their child's weight with regard to weight-based terms, terms that are the most motivating, preferred setting, and whether or not awareness of their child's weight status impact these preferences. METHODS: Parents of children ages 3 to 17 years (N = 349) presenting for health supervision visits completed a survey to assess the degree of offensiveness and motivation for change of commonly used weight-based terminology, as well as the preferred setting for discussion of weight. Parents were asked to assess their child's weight status using recommended terminology ("obese," "overweight," "healthy weight," "underweight"), and their responses were compared to the children's objective body mass index (BMI) percentile. RESULTS: The children had a median age of 10.3 years; 47.3% were female, 15.8% had overweight (85th-94th percentile BMI), and 11.5% had obesity (≥95th percentile BMI). Of children with overweight/obesity, 84.2% of parents underestimated their child's weight status. The least offensive terms were "at-risk weight," "BMI is high," "BMI is above 95%," and "unhealthy weight." The more offensive terms (P < .001) were "overweight" and "obese." The parent's perception of their child's weight did not affect offensiveness ratings. "Obese" was the strongest motivator for change (P < .001), and "unhealthy weight" was next. Well visits were preferred for discussing weight (P < .001). Most parents preferred to have the child remain in the room (P < .001), especially if the child was older (P < .001). CONCLUSIONS: Providers should use preferred terms when discussing excess weight regardless of a parent's perception of their child's status and should also consider the motivational value of the term. "Unhealthy weight" was both preferred and motivating, but "obese" was the most motivating.

Growth Hormone Therapy in Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is characterized by hyperphagia, obesity if food intake is not strictly controlled, abnormal body composition with decreased lean body mass and increased fat mass, decreased basal metabolic rate, short stature, low muscle tone, cognitive disability, and hypogonadism. In addition to improvements in linear growth, the benefits of growth hormone therapy on body composition and motor function in children with PWS are well established. Evidence is now emerging on the benefits of growth hormone therapy in adults with PWS. This review summarizes the current literature on growth hormone status and the use of growth hormone therapy in adults with PWS. The benefits of growth hormone therapy on body composition, muscle strength, exercise capacity, certain measures of sleep-disordered breathing, metabolic parameters, quality of life, and cognition are covered in detail along with potential adverse effects and guidelines for initiating and monitoring therapy.

Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function.

OBJECTIVE: The purpose of this study was to examine the effect of chronic swallowed glucocorticoids on adrenal function during the treatment of eosinophilic esophagitis (EoE) in children. METHODS: Serum cortisol levels were obtained in children with EoE pre- and post-treatment with swallowed glucocorticoids. Exclusion criteria included those on any additional steroid therapy. Once diagnosed with EoE by esophageal biopsy, subjects were treated based on current standard of care with either swallowed fluticasone or budesonide. At the time of follow-up, esophagogastroduodenoscopy and blood sampling was repeated. Both pre- and post-treatment serum cortisol samples were collected fasting, between 07:00 and 10:00, and determined using a competitive binding method assay. The distribution of differences in cortisol levels between the pre- and post-treatment samples satisfied the assumption for normality and were subsequently analyzed using the paired t-test. RESULTS: Pre- and post-treatment serum cortisol levels were examined in 14 children who met clinical and histological diagnostic criteria for EoE. Mean age was 10.1 years (range 2-17 years) with 71% male and 29% female subjects. Swallowed glucocorticoid treatment included fluticasone in 79% and budesonide in 21% of subjects. Mean dosage of fluticasone was 704 µg daily (range 220-880 µg daily) and budesonide 0.8 mg daily (range 0.5-1 mg daily), along with a mean treatment length of 17 weeks (range 8-43 weeks). No significant difference in serum cortisol was found following treatment with swallowed fluticasone or budesonide (mean change 1.9 µg/dL, p=0.75, SD of the change=21.2). CONCLUSIONS: Swallowed glucocorticoid therapy does not appear to significantly affect the adrenal axis in children, and therefore, may represent a safe therapy for EoE.

Endocrine manifestations and management of Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13. In infancy it is characterized by hypotonia with poor suck resulting in failure to thrive. As the child ages, other manifestations such as developmental delay, cognitive disability, and behavior problems become evident. Hypothalamic dysfunction has been implicated in many manifestations of this syndrome including hyperphagia, temperature instability, high pain threshold, sleep disordered breathing, and multiple endocrine abnormalities. These include growth hormone deficiency, central adrenal insufficiency, hypogonadism, hypothyroidism, and complications of obesity such as type 2 diabetes mellitus. This review summarizes the recent literature investigating optimal screening and treatment of endocrine abnormalities associated with PWS, and provides an update on nutrition and food-related behavioral intervention. The standard of care regarding growth hormone therapy and surveillance for potential side effects, the potential for central adrenal insufficiency, evaluation for and treatment of hypogonadism in males and females, and the prevalence and screening recommendations for hypothyroidism and diabetes are covered in detail. PWS is a genetic syndrome in which early diagnosis and careful attention to detail regarding all the potential endocrine and behavioral manifestations can lead to a significant improvement in health and developmental outcomes. Thus, the important role of the provider caring for the child with PWS cannot be overstated.