Sirolimus-Induced Hepatitis in Two Patients with Hyperinsulinemic Hypoglycemia

Sirolimus has been reported to be effective in the treatment of the diffuse form of congenital hyperinsulinism (CHI), unresponsive to diazoxide and octreotide, without causing severe side effects. Two newborns with CHI due to homozygous ABCC8 gene mutations were started on sirolimus aged 21 and 17 days, due to lack of response to medical treatment. A good response to sirolimus was observed. At follow-up after ten and two months of treatment, liver enzymes were found to be increased [serum sirolimus level 1.4 ng/mL (normal range: 5-15), aspartate aminotransferase (AST): 298U/L, alanine aminotransferase (ALT): 302U/L and serum sirolimus level: 9.9 ng/mL, AST: 261U/L, ALT: 275U/L, respectively]. In Case 1, discontinuation of the drug resulted in normalization of liver enzymes within three days. Two days after normalization, sirolimus was restarted at a lower dose, which resulted in a repeated increase in transferases. In Case 2, a reduction of sirolimus dose caused normalization of liver enzymes within ten days. When the dose was increased, enzymes increased within three days. Sirolimus was discontinued in both cases. The rapid normalization of liver enzyme levels after sirolimus withdrawal or dose reduction; elevation of transaminases after restart or dose increase and rapid normalization after sirolimus withdrawal were findings strongly suggestive of sirolimus-induced hepatitis. To the best of our knowledge, this is the first report of sirolimus-induced hepatitis in CHI. Sirolimus is a promising drug for CHI patients who are unresponsive to medical treatment, but physicians should be vigilant for adverse effects on liver function.

Leptin and neuropeptide Y levels in newborns.

AIM: Several studies have investigated leptin and neuropeptide Y (NPY) levels in children, but the information for newborns in the literature is limited. The purpose of this study was to determine leptin and NPY levels in 14- to 28-day-old newborns. MATERIALS AND METHODS: This prospective study was performed in Atatürk University Medical Faculty Research Hospital Neonatal Clinic, Erzurum, Turkey between July and December, 2014. Sixty-two 14- to 28-day-old neonates, 26 female and 36 male, were included. Age, height, and body weight of the patients were recorded. Feeding status was also recorded. The newborns were divided into two groups--those receiving breastfeeding only and those receiving breastfeeding and formula. Plasma leptin levels were measured using enzyme amplified sensitivity immunoassay (EASIA). RESULTS: The mean leptin level in 14- to 28-day-old female neonates was 4.25 ± 3.08 ng/mL, and the mean NPY level was 24.79 ± 9.87 ng/mL. The mean leptin level in 14- to 28-day male neonates was 3.49 ± 2.52 ng/mL, and the mean NPY level was 25.80 ± 9.58 ng/mL. No significant difference was determined between leptin (p=0.228) or NPY (p=0.144) in terms of feeding status. No significant difference was also observed between the sex in terms of leptin or NPY levels (leptin p=0.775 and NPY p=0.687). CONCLUSION: There were no differences in terms of feeding status and sex in leptin and NPY levels in the neonatal period.

The First Turkish Case of Hypoparathyroidism, Deafness and Renal Dysplasia (HDR) Syndrome.

Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant genetic disorder characterized by hypoparathyroidism, sensorineural deafness and renal dysplasia. We herein present the first Turkish patient with HDR syndrome, who has a p.R367X mutation. This report indicates that p.R367X is not a mutation specific for the Far Eastern populations and also that urological findings in infants with hypoparathyroidism should be carefully examined because clinical findings relating to the p.R367X mutation may show a variable age of onset.

Plasma Kisspeptin Levels in Newborn Infants with Breast Enlargement.

OBJECTIVE: Kisspeptin levels have been reported in children with premature thelarche, precocious puberty and adolescent gynecomastia, but there are no reports on kisspeptin levels in the neonatal period. This study aimed to investigate plasma kisspeptin hormone levels in newborns with and without breast enlargement. METHODS: Plasma kisspeptin levels and other related biochemical variables were investigated in this prospective study conducted on 40 (20 girls and 20 boys) newborn infants with breast enlargement and on 40 healthy control infants (20 girls and 20 boys). Two-milliliter venous blood samples were taken in hemogram tubes with K2EDTA. Kisspeptin assays were performed using the enzyme-immunoassay method. RESULTS: Mean plasma kisspeptin levels were 0.6 ± 0.2 ng/mL in the study group and 0.5 ± 0.2 ng/mL in the control group. Plasma kisspeptin concentrations were significantly higher in the study group (p=0.039) and also showed a correlation with serum prolactin levels (p=0.006). Significant correlations were also determined between plasma kisspeptin and luteinizing hormone concentrations (p=0.05, r=0.312). CONCLUSION: The findings of this study suggest that plasma kisspeptin and serum prolactin levels may be involved in the physiopathology of breast enlargement in newborns.

Evaluation of Lymphocyte Subgroups in Children With Down Syndrome.

In this study, lymphocyte subgroups including blood CD3, CD4, CD8, CD4/CD8, CD19, and CD16.56 values were analyzed in children with Down syndrome (DS). The study includes 85 children with DS, followed at Department of Pediatrics, Faculty of Medicine, Yüzüncü Yil University and 64 healthy age-matched control participants. Blood CD3, CD4, CD8, CD4/CD8, CD19, and CD16.56 values were examined in both the groups. Significantly decreased blood CD3, CD4, and CD19 values were found in the study group (P < .05) when compared with the control group. In conclusion, we would like to emphasize that blood CD3, CD4, and CD19 levels were found to be decreased in children with DS. Based on these finding, we think that these decreased lymphocyte subgroups might be responsible for increased susceptibility to infections in children with DS.

Combined occurrence of Alström syndrome and bronchiectasis.

Alström syndrome (Online Mendelian Inheritance in Man ALMS #203800) is a rare hereditary disorder caused by mutations in the gene ALMS1. This rare disorder's characteristics are cone-rod dystrophy resulting in blindness in childhood, insulin-resistant type 2 diabetes mellitus, truncal obesity, progressive sensorineural hearing loss, dilated cardiomyopathy, craniofacial features, hypothyroidism, elevation in liver transaminases, renal insufficiency, gonadal dysfunction, and menstrual irregularities. A 13.5-year-old girl was admitted to the hospital for complaints of excessive water consumption and urination over the previous 2 years. The patient's parents were third-degree relatives. At physical examination, hyperpigmentation was present over the areola and acanthosis nigricans under the arms and on the neck. Audiologic examination revealed bilateral sensorineural hearing loss, and bilateral cataract was determined at ocular examination. The patient was monitored by the chest diseases department due to bronchiectasis. HbA1c was 13.1%. In mutation screening study, 2 novel mutations c.5586T>G; p.Tyr1862* and c.2905insT; p.L968fs*4 were detected in the ALMS1 gene. Saccharin test was positive. We emphasize that Alström syndrome may be complicated by bronchiectasis.

Thyroid functions and trace elements in pediatric patients with exogenous obesity.

Obesity is a multifactorial disease developing following impairment of the energy balance. The endocrine system is known to be affected by the condition. Serum thyroid hormones and trace element levels have been shown to be affected in obese children. Changes in serum thyroid hormones may result from alterations occurring in serum trace element levels. The aim of this study was to evaluate whether or not changes in serum thyroid hormone levels in children with exogenous obesity are associated with changes in trace element levels. Eighty-five children diagnosed with exogenous obesity constituted the study group, and 24 age- and sex-matched healthy children made up the control group. Serum thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (TG), selenium (Se), zinc (Zn), copper (Cu), and manganese (Mn) levels in the study group were measured before and at the third and sixth months of treatment, and once only in the control group. Pretreatment fT4 levels in the study group rose significantly by the sixth month (p = 0.006). Zn levels in the patient group were significantly low compared to the control group (p = 0.009). Mn and Se levels in the obese children before and at the third and sixth months of treatment were significantly higher than those of the control group (p = 0.001, p = 0.001). In conclusion, fT4, Zn, Cu, Mn, and Se levels are significantly affected in children diagnosed with exogenous obesity. The change in serum fT4 levels is not associated with changes in trace element concentrations.

Serum vitamin D levels in children with recurrent otitis media.

The aims of this study were to evaluate serum vitamin D levels in cases of recurrent otitis media and investigate the effect of vitamin D therapy on the risk of re-occurrence of the disease. This prospective study was performed by comparing serum vitamin D levels in children with recurrent otitis media and healthy children. Eighty-four children between 1 and 5 years of age and diagnosed with recurrent otitis media were enrolled as the study group. One hundred-and-eight healthy children with similar demographic characteristics were enrolled as the control group. Patients were divided into groups according to their serum 25(OH) vitamin D levels. In patients with low initial serum vitamin D levels, vitamin D therapy was administered in addition to conventional treatment for otitis media. Mean serum 25(OH) vitamin D level in the study group was 11.4 ± 9.8 ng/mL Serum 25(OH) vitamin D levels were below 20 ng/mL in 69 % (n = 58) of cases in this group. In the control group, mean serum 25(OH) vitamin D level was 29.2 ± 13.9 ng/mL and was below 20 ng/mL in 30 % (n = 32) of cases. Comparison of serum 25(OH) vitamin D levels and PTH in the study and control groups revealed a statistically significant difference (p < 0.05). Treatment was initiated in cases diagnosed with vitamin D deficiency, and patients were followed up in due course. The only episodes detected over the course of 1-year follow-up were one attack in five patients and two attacks in two. We believe that co-administration of supplementary vitamin D together with conventional treatments is appropriate in the management of upper respiratory infections such as otitis media.

Infantile digital fibromatosis (inclusion body fibromatosis) observed in a baby without finger involvement.

A 9-day-old male baby was hospitalized after his birth due to some swells under the skin. The hard consistency nodules observed under the skin all over the body of the patient were of different size, and presented lesions, among which the biggest was 1 × 1 cm. No lesions were observed on the fingers. By superficial ultrasonography, multiple isoechoic hypoechoic lesions were observed among the muscle plan. In thoracolumbar magnetic resonance imaging, multiple massif lesions retaining peripheral contrast (the biggest was 1.7 × 1.4 cm large) had been observed under the skin muscle plans, between the muscles of the extremities. The biopsy was positive for smooth muscle actin, but negative for desmin, S100, and CD34. These findings were diagnosed as infantile digital fibromatosis (IDF) (inclusion body fibromatosis). The case was presented with an objective to illustrate and remind that IDF can be observed in babies without finger involvement.

H1N1 influenza A virus Related Pneumonia and Respiratory Failure.

Influenza viruses are common respiratory pathogens in humans and can cause serious infection that leads to the development of pneumonia. In this study, the clinical and laboratory features of 36 patients from Turkey who are hospitalized in intensive care unit due to pandemic influenza A (H1N1) associated pneumonia and respiratory failure were retrospectively evaluated. The most common symptoms were cough and fever. Consolidation (36.1 %) and interstitial changes (30.6 %) were the most frequently identified findings on chest radiographs at the time of admission. Six of the patients (16.7 %) died. Mortality occurred in 3 of 13 patients (23.1 %) with underlying disease, whilst it occurred in only 3 of 23 patients (13 %) who were previously healthy. Mortality was found to be significantly associated only with an elevated lactate dehydrogenase level. A significant relationship was determined only between the presence of lymphopenia and acute respiratory distress syndrome and the need for intensive care treatment. The average time elapsed from the onset of the symptoms until admission was 8.67 ± 2.87 days for the patients died, and 6.0 ± 3.8 days for the patients survived.

Retrospective clinical and laboratory evaluation of children with brucellosis.

BACKGROUND: Acute brucellosis is a zoonotic disease seen in childhood, with non-specific complaints and clinical findings that can affect the locomotor, gastrointestinal, genitourinary, hematologic, cardiovascular, respiratory, and central nervous systems. Particularly in endemic regions, it occurs as a result of consumption of unpasteurized milk and dairy products. In this study, clinical and laboratory findings of children with acute brucellosis are presented. METHODS: Data for 147 patients, aged 2-16 years, were evaluated retrospectively. RESULTS: The most frequent complaints and clinical findings were abdominal pain and fever. Other complaints and clinical findings included arthralgia, myalgia, loss of appetite, weakness, sweating, fatigue, headache, arthritis, hepatomegaly, and splenomegaly. Anemia was the most frequent hematological abnormality detected; other abnormalities included leukopenia, thrombocytopenia, and pancytopenia. CONCLUSION: Childhood brucellosis can cause non-specific complaints and particularly anemia and leukopenia as hematological abnormalities. It is easily treated, however, with appropriate antibiotics.

The evaluation of children with monosymptomatic nocturnal enuresis for attention deficit and hyperactivity disorder.

OBJECTIVE: Monosymptomatic nocturnal enuresis (MNE) and attention deficit and hyperactivity disorder (ADHD) are multifactorial disorders and biological, social, and psychological factors may play significant roles in the development of both. Children with enuresis display a higher prevalence of ADHD compared to the normal population. This study aimed to evaluate the relationship between MNE and ADHD. METHODS: A total of 64 children between the ages of 6 and 13 years who were referred due to primary MNE, their parents, and 42 healthy control cases, were evaluated in terms of attention deficit and hyperactivity by a child psychiatrist using the DSM-IV-2000-TR diagnosic scale. RESULTS: Of the children with enuresis, 17 had predominantly inattentive type (26.6%), nine had predominantly hyperactive-impulsive type (14.1%), and eight had combined type (12.5%). In the control group, two cases had predominantly inattentive type (4.8%), two cases had predominantly hyperactive-impulsive type (4.8%), and one had combined type (2.4%). CONCLUSIONS: The prevalence of ADHD is higher in children with MNE compared to the normal population. As attention deficit may also negatively effect the treatment of enuresis, children with MNE should be evaluated in terms of attention deficit and those with positive symptoms should be provided with psychosocial support.

A case of idiopathic intracranial hypertension related with vesicoureteral reflux.

Pseudotumor cerebri is idiopathic intracranial hypertension. The etiology of this syndrome has not been fully clarified. Excess cerebrospinal fluid production, scarcity of cerebrospinal fluid absorption, intracranial venous pressure elevation, increased intracranial blood volume are all thought to be responsible. The symptoms of the disease may be ordered according to prevalence as follows: headache due to increased intracranial pressure, blurred vision and diplopia. A thirteen-year-old female patient was brought in with complaints of headache, double and blurred vision. Systemic arterial hypertension (140/70 mmHg) was determined. Vesicoureteral reflux was detected as the hypertension etiology. In this article a rare pseudotumor cerebri case is presented secondary to vesicoureteral reflux which caused hypertension.

Clinical outcome and magnetic resonance imaging findings in infants with hypoglycemia.

The authors examined clinical outcome and cranial magnetic resonance imaging (MRI) findings in infants with hypoglycemia to determine the effects of hypoglycemia on the developing brain. A total of 110 infants with hypoglycemia were included in the study. Of the patients, 36 were females and 74 were males. The age of the infants was between 1 day and 22 months. Of the 110 infants, 47 were preterm neonates, 40 were term neonates, and 23 were older than 28 days. No difference in serum glucose level was noted between symptomatic and asymptomatic infants. The most common observed abnormal findings were hyperintense lesions, encephalomalacia, and cerebral atrophy. Abnormal MRI findings were found in 4% of preterm infants, in 32.5% of term infants, and in 43.5% of older infants. Abnormal MRI findings were statistically significantly more common in symptomatic infants than in asymptomatic infants. Of the infants, 45.5% of hypoglycemic infants had cerebral palsy and/or cerebral palsy plus epilepsy.