A Neonatal Case of Infantile Malignant Osteopetrosis Presenting with Thrombocytopenia and Hypotonicity: A Novel Mutation in Chloride Voltage-Gated Channel 7 Gene.

Autosomal recessive osteopetrosis is also known as infantile malignant osteopetrosis (IMO). The clinical course is often serious and if left untreated, it is fatal in the 1st year of life. Diagnosis is challenging and often delayed or misdiagnosed. Herein, we present an infant girl who was diagnosed with IMO during evaluations for her hypotonicity and thrombocytopenia. A novel mutation of the chloride voltage-gated channel 7 (CLCN7) gene was also reported. A 10-day-old female patient was referred to our hospital for evaluation of hypotonicity. Her physical examination was normal, other than hypotonicity. Laboratory analysis revealed thrombocytopenia and hypocalcemia. In the progress, while she was followed in outpatient clinic, hepatosplenomegaly was detected at the age of 3 months. IMO was suspected with the findings of hepatosplenomegaly, cytopenia, hypocalcemia, difficulty of obtaining bone marrow, peripheral smear findings, and hearing loss. The X-ray of the bones was consistent with IMO. A novel pathogenic homozygous c.1504>T (p.Arg502Trp) mutation in CLCN7 gene was revealed. IMO is a rare disorder and it is important to differentiate this entity for better clinical outcome. The presence of neurological and hematological findings, organomegaly, hearing loss, and vision disorders must attract attention to IMO.

Evaluation of Sporadic and Familial Cases with Craniofrontonasal Syndrome: A Wide Clinical Spectrum and Identification of a Novel EFNB1 Gene Mutation.

Craniofrontonasal syndrome (CFNS) is a rare X-linked genetic disorder which is characterized by coronal synostosis, widely spaced eyes, a central nasal groove, and various skeletal anomalies. Mutations in the EFNB1 gene in Xq13.1 are responsible for familial and sporadic cases. In the present study, we aimed to evaluate the clinical characteristics and molecular results of 4 patients with CFNS. Genomic DNA was extracted from the peripheral blood lymphocytes of all patients and their parents, and Sanger sequencing of the EFNB1 gene was performed. A novel EFNB1 gene mutation (c.65delG; p.Cys22SerfsTer24) was detected in a newborn who had only dysmorphic facial features and bicornuate uterus. The other 3 patients (2 familial cases and 1 sporadic case) shared the same mutation (c.196C>T; p.R66X). However, the clinical features of these patients were highly variable. Additionally, central (meso-axial) polydactyly and deep palmar creases were detected, which have not been previously reported. CFNS has a wide clinical spectrum, but there is no clear genotype-phenotype correlation. However, central (meso-axial) polydactyly and deep palmar creases may be part of the clinical spectrum seen in CFNS. In addition, our findings expand the mutational spectrum in patients with CFNS.

The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aim: We aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH). Materials and methods: Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) "uncontrolled" [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) "controlled" [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system. Results: There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status. Conclusion: In this study, the CIMT values of CAH cases were similar to those of healthy subjects.

Novel Ocular and Inner Ear Anomalies in a Patient with Myhre Syndrome.

Myhre syndrome is a rare autosomal dominant multisystemic disorder. Typical features of this disorder include distinctive facial appearance, deafness, intellectual disability, cardiovascular abnormalities, short stature, brachydactyly, and skeletal anomalies. Gain-of-function mutations in the SMAD4 gene are responsible for this syndrome. Herein, we present a 9.6-year-old Turkish girl with molecularly confirmed Myhre syndrome who had novel findings including bilateral Axenfield Rieger anomaly with secondary glaucoma and bilateral enlarged vestibular aqueducts.

Obesity-related thyroiditis in childhood: relationship with insulin resistance.

Background Thyroid dysfunction is the most common hormonal abnormality in obesity. It should actually be considered as an adaptation response to fat excess. However, little has been reported on the morphology of the thyroid gland, and no data regarding the relationship between thyroid gland changes and metabolic parameters are available in obese adolescents. Objective The study aimed to evaluate the frequency of non-autoimmune thyroiditis in obese adolescents and compare the metabolic status of patients with or without thyroiditis. Methods A total of 218 obese children and 49 age-matched control healthy children were included. Thyroid ultrasonography (USG) was performed in all participants, as well as thyroid hormone levels, thyroid antibodies (Abs), lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (HsCRP) were determined. Obese children were divided into three groups according to the presence of thyroid autoantibodies and USG findings of thyroiditis (Group-1: Abs [-], normal thyroid morphology/Group-2: Abs [+], abnormal thyroid morphology/Group-3: Abs [-], abnormal thyroid morphology). The relationship between body mass index, metabolic parameters and thyroid gland status was analyzed. Results Seventy-two of 218 obese patients (33%) had non-autoimmune thyroiditis (Group-3). The rate of insulin resistance was significantly higher in Group-3 than in Group-1 (p = 0.024). Similarly, the frequency of metabolic syndrome (MS) was higher in Group-3 (44.3%) than in Group-1 (27.1%) (p = 0.014). Conclusions Obese adolescents with non-autoimmune thyroiditis had a higher incidence of insulin resistance. This finding supported the hypothesis that insulin resistance may have an effect on thyroid morphology. Further randomized trials investigating this relationship are required.

Magnesium and Anti-phosphate Treatment with Bisphosphonates for Generalised Arterial Calcification of Infancy: A Case Report

Generalized arterial calcification of infancy (GACI) is a rare autosomal-recessive disorder, characterized by calcification of the internal elastic lamina, fibrotic myointimal proliferation of muscular arteries and resultant arterial stenosis. Treatment with bisphosphonates has been proposed as a means of reducing arterial calcifications in GACI patients, although there is no formalized treatment approach. The case reported here was a patient with severe GACI diagnosed at three months of age who had no response to bisphosphonate treatment, but clinically improved after the initiation of magnesium and anti-phosphate (using calcium carbonate) treatments. In patients unresponsive to bisphosphonate, magnesium and anti-phosphate treatment may be attempted.

Pulmonary hydatid cyst disease mimicking necrotizing pneumonia in a child with leukocytoclastic vasculitis.

The diagnosis and management of pulmonary hydatid cyst disease represents an important clinical problem in countries of the world that are endemic to echinococcal infection. Atypical clinical and radiologic findings including multiple cavitary lesions in the lung and pleural effusion may lead to misdiagnosis or delay in diagnosis in these patients. We report a patient who was followed up in our hospital with rashes and, clinical and radiologic findings of necrotizing pneumonia in whom there was no response to broad spectrum antibiotherapy. Lung computed tomography showed multiple thick-walled cystic lesions and pleural effusion and the diagnosis of pulmonary hydatid cyst disease was confirmed by surgical and serologic examinations. Antibiotic treatment was changed to albendazole 10 mg/kg/day. There was no liver involvement in terms of cyst hydatid disease with ultrasonographic examination. Skin biopsy showed leukocytoclastic vasculitis. Complete clinical and radiologic improvement was achieved in three months and albendazole treatment lasted six months.

Intratubular large cell hyalinizing Sertoli cell tumor of the testis presenting with prepubertal gynecomastia: a case report.

Intratubular large cell hyalinizing Sertoli cell neoplasia (ITLCHSCN) resulting from Sertoli cells of the testis are mainly reported in young adults and these are rarely seen in childhood. The most common presenting symptoms of the patients diagnosed with ITLCHSCN are gynecomastia, enlargement in the testicles, increase in growth velocity, and advanced bone age. Symptoms are basically resulting from increased aromatase enzyme activity in Sertoli cells. In this case report, an eight-and-a-half-year-old case presenting with complaint of bilateral gynecomastia since two years, showing no endocrine abnormality in laboratory during two years of follow-up, determined to have progression in bilateral gynecomastia, increase in testicular volumes, advanced bone age, increase in growth velocity in the clinical follow-up, and diagnosed with ITLCHSCN after testis biopsy was presented.

Myelin Oligodendrocyte Glycoprotein Antibody Persistency in a Steroid-Dependent ADEM Case.

Myelin oligodendrocyte glycoprotein (MOG) is a candidate target antigen in demyelinating central nervous system diseases, including acute disseminated encephalomyelitis (ADEM), neuromyelitis optica, and multiple sclerosis. It may give prognostic information regarding monophasic or recurrent course of the disease. MOG antibodies have been shown to be positive in high titers during the first episode of ADEM with rapidly decreasing to undetectable limits after recovery. However, persistent MOG antibodies are considered as a predicting factor for multiple sclerosis, optic neuritis relapses, and incomplete recovery of ADEM. Here we report a unique case with persistent MOG antibodies presented with multiphasic ADEM-like attacks. A 6-year-old girl was consulted with encephalopathy, gait disturbance, and oculomotor nerve palsy. Periventricular white matter lesions were seen on cranial magnetic resonance imaging studies. ADEM was diagnosed and treated with steroid. During follow-up, she experienced repeated episodes after steroid therapy termination. We were able to search MOG antibody at the ninth attack. The positivity of this antibody remained. It was thought to be associated with steroid-dependent course, and azathioprine and intravenous human immunoglobulin treatment were added. Patients with persistent MOG antibodies may benefit from addition of immunosuppressant agents, which may decrease the number of attacks.

Recovery of Central Fever after GH Therapy in a Patient with GH Deficiency Secondary to Posttraumatic Brain Injury.

Growth hormone (GH) deficiency is the most common pituitary hormone deficiency after traumatic brain injury. Patients with GH deficiency have a reduced sweating capacity which increases the risk of developing hyperthermia. To the best of our knowledge, central fever that developed due to GH deficiency and improved with GH treatment has not yet been reported. In this article, we present a case of dramatic improvement of central fever with recombinant human GH therapy in a patient with posttraumatic GH deficiency.