ESPE Abstracts (2018) 89 P-P2-193

aHacettepe University Medical School, Department of Pediatrics, Division of Pediatric Endocrinology, Ankara, Turkey; bHacettepe University Medical School, Department of Medical Genetics, Ankara, Turkey; cHacettepe University Medical School, Department of Pediatrics, Division of Pediatric Genetics, Ankara, Turkey

Introduction: Costello syndrome is a rare RASopathy that is associated with such characteristics as prenatal overgrowth, postnatal growth retardation, mental-motor retardation, coarse face appearance, loose skin on the neck, hands and feet, cardiovascular abnormalities, deep palmar and plantar lines and a predisposition to various types of cancer. Several endocrine disorders, including growth hormone deficiency, adrenal failure, glucose intolerance, hyperprolactinemia and hypoglycemia, have been defined in cases with Costello syndrome. In the present report, we describe a patient diagnosed with Costello syndrome accompanied by a clinical picture of hyperinsulinemic hypoglycemia and whose responsive to diazoxide.

Case: A 36-week-old female patient with a birth weight of 3,800 grams showed postnatal growth and developmental retardation, and a physical examination revealed a body weight of 6,120 grams, a height of 63 cm, coarse face appearance, and deep palmar and plantar lines. Echocardiography showed pulmonary valve stenosis. A whole exome sequencing was performed to rule out storage diseases and to confirm the diagnosis of Costello syndrome which was suspected based on clinical findings. The Costello syndrome was confirmed by the presence of a heterozygous missense mutation in HRAS gene. The cranial MRI showed a diffuse thin appearance in corpus callosum. The patient was examined by the endocrinology department at the age of 13 months because of hypoglycemia. The patient’s serum glucose was 38 mg/dl, and the concurrently measured insulin:2.8 mcIU/ml, c-peptide:1.8 ng/ml, cortisol:26 mcg/dl, growth hormone (GH): 8.72 ng/ml, NH3:123 mcg/dl (N:20-120), lactic acid:13.69 mg/dl (N:4.5-19.8), pyruvate:1.62 mg/dl (N:0.3-0.9), tandem mass spectrometry, plasma and urine amino acid profiles, and urine organic acid analyses were normal. Hyperinsulinism was suspected, since the levels of insulin and c-peptide were elevated at the time of hypoglycemia, and an exaggerated glucose response was seen in a glucagon test. Thyroid function tests and prolactin levels were normal. IGF-1:4.66 ng/ml(<-3SD), IGFBP-3:1082.93ng/ml (<-3 SD), and peak GH at glucagon stimulation: 9.07 ng/ml. Blood glucose monitoring indicated episodes of fasting hypoglycemia and postprandial hyperglycemia. Diazoxide of 10 mg/kg/day was initiated for hyperinsulinemic hypoglycemia, which was resolved, with no new episodes of postprandial hyperglycemia occurring.

Conclusion: Very few cases of Costello syndrome accompanied by hyperinsulinemic hypoglycemia have been reported, and the etiology of this condition is yet to be understood, although patients respond well to diazoxide.

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