Journal of Clinical Research in Pediatric Endocrinology

Journal Information
ISSN / EISSN : 13085727 / 13085735
Current Publisher: Galenos Publishing House (10.4274)
Current Coverage

Latest articles in this journal

Emregül Işık, Huseyin Demirbilek, Jayne A. L. Houghton, Sian Ellard, Sarah E. Flanagan, Khalid Hussain
Journal of Clinical Research in Pediatric Endocrinology, Volume 11, pp 82-87; doi:10.4274/jcrpe.galenos.2018.2018.0077

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children. Recessive inactivating mutations in the ABCC8 and KCNJ11 genes account for approximately 50% of all CHI cases. Hyperinsulinaemic hypoglycaemia in infancy and diabetes in later life have been reported in patients with HNF1A, HNF4A and ABCC8 mutations. Herein, we present a child who was diagnosed with CHI at birth, then developed diabetes mellitus at the age of nine years due to a novel homozygous missense, p.L171F (c.511C>T) mutation in exon 4 of ABCC8. The parents and one sibling were heterozygous carriers, whilst a younger sibling who had transient neonatal hypoglycemia was homozygous for the mutation. The mother and (maternal) uncle, who was also heterozygous for the mutation, developed diabetes within their third decade of life. The preliminary results of sulphonylurea (SU) treatment was suggestive of SU responsiveness. Patients with homozygous ABCC8 mutations can present with CHI in the newborn period, the hyperinsulinism can show variability in terms of clinical severity and age at presentation and can cause diabetes later in life. Patients with homozygous ABCC8 mutations who are managed medically should be followed long-term as they may be at increased risk of developing diabetes after many years.
Nicole Coles, Ian Comeau, Tatiana Munoz, Jennifer Harrington, Roberto Mendoza-Londono, Andreas Schulze, Sari Kives, Binita M. Kamath, Jill Hamilton
Journal of Clinical Research in Pediatric Endocrinology, Volume 11, pp 100-103; doi:10.4274/jcrpe.galenos.2018.2018.0110

McCune-Albright syndrome (MAS) is a rare genetic disorder characterized by café-au-lait macules, polyostotic fibrous dysplasia and multiple endocrinopathies. Liver involvement, although described, is a rare complication. We review the case of a child with MAS whose initial presentation was characterized by severe neonatal cholestasis. The case demonstrates a severe phenotype of persistent cholestasis in MAS requiring liver transplantation. This phenotype has been previously considered to be a more benign feature. This case highlights the importance of consideration of MAS as an uncommon but important cause of neonatal cholestasis. Early diagnosis may allow for prompt recognition and treatment of other endocrinopathies.
Sze M. Ng, Donatella Pintus, Mark A Turner
Journal of Clinical Research in Pediatric Endocrinology, Volume 11, pp 104-108; doi:10.4274/jcrpe.galenos.2018.2018.0162

Recent studies have shown that small for gestational age (SGA) term infants undergo catch-up growth during infancy but there is limited studies on early growth outcomes of extreme premature SGA infants. The aim of this study was to compare factors associated during birth in extremely premature infants less than 28 weeks’ gestation who were born SGA (<10th percentile for gestational age) with those who were born appropriate-for-gestational age (AGA) (10th-89th percentile) and to determine whether there was catch-up growth at term equivalence. One hundred fifty-three extreme premature infants (89 males) born below 28 weeks’ gestation were prospectively recruited. All infants had auxological measurements undertaken and prospective data on pregnancy, maternal factors, perinatal and postnatal data obtained. SGA infants at birth had significantly higher Clinical Risk Index for Babies scores and mortality, lower birth weight, smaller head circumference, smaller mid arm circumference and shorter leg length at time of birth compared with AGA infants. However, at term equivalence, weight and leg length of were not significant between AGA and SGA infants born at extreme prematurity. Our study shows that extreme premature SGA infants have appropriate catch-up growth by the time they reach term equivalence suggesting that postnatal nutrition and care are important determinants of catch-up growth in SGA infants.
Rabia Miray Kisla Ekinci, Fatih Gürbüz, Sibel Balci, Atil Bisgin, Mehmet Taştan, Bilgin Yüksel, Mustafa Yılmaz
Journal of Clinical Research in Pediatric Endocrinology, Volume 11, pp 94-99; doi:10.4274/jcrpe.galenos.2018.2018.0134

Inactivating autosomal recessive mutations in fibroblast growth factor 23 (FGF23), klotho (KL) and polypeptide N-acetylgalactosaminotransferase 3 (GALNT3) genes lead to a rare disorder, hyperphosphatemic familial tumoral calcinosis (HFTC). Patients with HFTC present with hyperphosphatemia and tumor like soft tissue calcifications. Although 78% of patients develop their first symptoms between the ages of 2-13 years, diagnosis is usually delayed until adulthood. Some individuals with the same genetic defect develop a condition named hyperphosphatemic hyperostosis syndrome. Herein we report two siblings suffering from periarticular, warm, hard and tender subcutaneous masses. Subcutaneous calcifications were present on X-ray and biopsy results were consistent with calcinosis in both patients. Laboratory results showed marked hyperphosphatemia and elevated renal tubular phosphate reabsorption rates, normal renal function tests and normal serum 25-hydroxyvitamin D levels. Thus, we suspected HFTC and performed next generation sequencing for the GALNT3 gene, reported as the most frequent cause. A novel homozygote P85Rfs*6 (c.254_255delCT) mutation in GALNT3 was identified in both siblings. Our report adds two new patients to the literature about this rare genetic disease and suggests that small deletions in the GALNT3 gene may be related with HFTC phenotype.
Alejandro F. Siller, Alex Shimony, Marwan Shinawi, Ina Amarillo, Louis P. Dehner, Katherine Semenkovich, Ana Maria Arbelaez
Journal of Clinical Research in Pediatric Endocrinology, Volume 11, pp 88-93; doi:10.4274/jcrpe.galenos.2018.2018.0005

We report a detailed phenotypic, cytogenetic and molecular characterization of a patient prenatally diagnosed with Turner syndrome (TS). In addition to having typical TS clinical characteristics including webbed neck, high arched palate and coarctation of the aorta, the patient had features less frequently seen in TS. These included recurrent parathyroid adenomas, growth along the 75th-90th centiles on the TS height curve despite minimal treatment with growth hormone, behavioral problems and evidence of gonadal dysgenesis with testicular-like structures, such as seminiferous tubules lined by Sertoli cells and a contiguous nodule of Leydig cells. While fluorescence in situ hybridization (FISH) failed to detect Y-chromosome material in gonadal tissue or blood samples, chromosomal microarray analysis (CMA) confirmed X monosomy and a 4.69 Mb copy number loss on 1q31.2q31.3 (bp 192,715,814 to 197,401,180). This region contains the CDC73 gene which has been associated with hyperparathyroidism-jaw tumor syndrome, features of which include recurrent, functional parathyroid adenomas and behavioral issues. This case illustrates how atypical features in a TS patient, such as robust growth and recurrent parathyroid adenomas, may suggest an underlying molecular etiology that should be explored by additional genetic diagnostic modalities. It is therefore appropriate in such cases to conduct further genetic testing, such as CMA and FISH, to explore other diagnostic possibilities and possibly prevent further complications.
Amanda R. Dahl, Radhika Dhamija, Alaa Al Nofal, Siobhan T. Pittock, W. Frederick Schwenk, Seema Kumar
Journal of Clinical Research in Pediatric Endocrinology, Volume 10, pp 79-82; doi:10.4274/jcrpe.4807

Klinefelter syndrome is the most frequent chromosomal aneuploidy in males occurring in about 1 in 660 males. Epidemiological studies have demonstrated increased risk of type 1 diabetes and type 2 diabetes in adults with Klinefelter syndrome. There is only one previous report of neonatal diabetes in a patient with Klinefelter syndrome. We report transient neonatal diabetes due to a pathogenic heterozygous variant in KCNJ11 in a male infant with Klinefelter syndrome. A 78-day old male infant was noted to have sustained hyperglycemia with serum glucose ranging between 148 mg/dL (8.2 mmol/L) and 381 mg/dL (21.2 mmol/L) three days after undergoing a complete repair of an atrioventricular defect. Hemoglobin A1c was 6.6%. The patient was born at term with a birth weight of 2.16 kg following a pregnancy complicated by gestational diabetes that was controlled with diet. The patient was initially started on a continuous intravenous insulin drip and subsequently placed on subcutaneous insulin (glargine, human isophane and regular insulin). Insulin was gradually decreased and eventually discontinued at seven months of age. Chromosomal microarray at 11 weeks of age showed XXY and a panel-based, molecular test for neonatal diabetes revealed a pathogenic heterozygous variant c.685G>A (p.Glu229Lys) in KCNJ11. The patient is now 34 months old and continues to have normal fasting and post-prandial glucose and HbA1C levels. The patient will need prospective follow up for assessment of his glycemic status. To our knowledge this is the second reported case of neonatal diabetes in an infant with Klinefelter syndrome and the first due to a mutation in the KCNJ11 in a patient with Klinefelter syndrome.
Feryal Karahan, Elvan Çağlar Çıtak, Emel Yaman, Mehmet Alakaya, Fatih Sağcan, Eda Bengi Yılmaz, Funda Kuş, Iclal Gürses, Yüksel Balcı
Journal of Clinical Research in Pediatric Endocrinology, Volume 10, pp 87-90; doi:10.4274/jcrpe.4905

Patients with complete XY gonadal dysgenesis (GD) show a high predisposition to germ cell tumors (GCT). Patients with coexistence of GCT and GD have been reported previously. Here we present a 15-year-old girl with mixed GCT and GD who also developed an intra-abdominal synovial sarcoma one year after the treatment. This is the first report, to our knowledge, of synovial sarcoma associated with XY GD.
Jens Otto Broby Madsen, Sabrina Sauer, Bodo Beck, Jesper Johannesen
Journal of Clinical Research in Pediatric Endocrinology, Volume 10, pp 83-86; doi:10.4274/jcrpe.4841

Idiopathic infantile hypercalcemia (IIH) was associated with vitamin-D supplementation in the 1950’s. Fifty years later, mutations in the CYP241A gene, involved in the degradation of vitamin-D, have been identified as being a part of the etiology. We report a case of a 21-month old girl, initially hospitalized due to excessive consumption of water and behavioral difficulties. Blood tests showed hypercalcemia and borderline high vitamin-D levels. Renal ultrasound revealed medullary nephrocalcinosis. An abnormality in vitamin-D metabolism was suspected and genetic testing was performed. This revealed the patient to be compound heterozygous for a common (p.E143del) and a novel (likely) disease-causing mutation (p.H83D) in the CYP24A1 gene. The hypercalcemia normalized following a calcium depleted diet and discontinuation of vitamin-D supplementation. Increased awareness of the typical symptoms of hypercalcemia, such as anorexia, polydipsia, vomiting and failure to thrive, is of utmost importance in diagnosing IHH early and preventing long-term complications such as nephrocalcinosis. Further identification of as many disease-causing mutations in the CYP24A1 gene as possible can help identification of predisposed individuals in whom vitamin-D supplementation should be reconsidered.
Assimina Galli‐Tsinopoulou, Anastasios Serbis, Eleni P. Kotanidou, Eleni Litou, Vaia Dokousli, Konstantina Mouzaki, Pavlos Fanis, Vassos Neocleous, Nicos Skordis
Journal of Clinical Research in Pediatric Endocrinology, Volume 10, pp 74-78; doi:10.4274/jcrpe.4829

17-beta hydroxysteroid dehydrogenase type 3 (17βHSD-3) enzyme catalyzes the conversion of androstenedione (Δ4) to testosterone (T) in the testes of the developing fetus, thus playing a crucial role in the differentiation of the gonads and in establishing the male sex phenotype. Any mutation in the encoding gene (HSD17B3) can lead to varying degrees of undervirilization of the affected male, ranging from completely undervirilized external female genitalia to predominantly male with micropenis and hypospadias. We present here an infant who was referred to our clinic because of ambiguous genitalia at birth. Gonads were palpable in the inguinal canal bilaterally and no Müllerian structures were identified on pelvic ultrasound. Because of a low T/Δ4 ratio after a human chorionic gonadotropin stimulation test, a tentative diagnosis of 17βHSD-3 deficiency was made which was confirmed after genetic analysis of the HSD17B3 gene of the patient. The molecular analysis identified compound heterozygosity of two previously described mutations and could offer some further validation for the idea of a founder effect for 655-1;G→A mutation in the Greek population.
Semra Çetinkaya, Tülay Güran, Erdal Kurnaz, Melikşah Keskin, Elif Sağsak, Senay Savaş Erdeve, Jenifer P. Suntharalingham, Federica Buonocore, John C. Achermann, Zehra Aycan
Journal of Clinical Research in Pediatric Endocrinology, Volume 10, pp 68-73; doi:10.4274/jcrpe.4638

Proopiomelanocortin (POMC) deficiency is a rare monogenic disorder with early-onset obesity. Investigation of this entity have increased our insight into the important role of the leptin-melanocortin pathway in energy balance. Here, we present a patient with POMC deficiency due to a homozygous c.206delC mutation in the POMC gene. We discuss the pathogenesis of this condition with emphasis on the crosstalk between hypothalamic and peripheral signals in the development of obesity and the POMC-melanocortin 4 receptors system as a target for therapeutic intervention.