Congenital Adrenal Hyperplasia with Combined 21-hydroxylase deficiency and 17α-hydroxylase/17,20-lyase deficiency: An undervirilized male.

21-hydroxylase deficiency stands as the most prevalent form of congenital adrenal hyperplasia, primarily resulting from mutations in the CYP21A2 gene. On the other hand, mutations within the CYP17A1 gene lead to 17α-hydroxylase/17,20-lyase enzyme deficiencies. The scarcity of 17-OH deficiency is noteworthy, accounting for less than 1% of all congenital adrenal hyperplasia cases. The male patient, born from a first-degree cousin marriage, exhibited several symptoms, including left undescended testis, micropenis, penile chord, left sensorineural hearing loss, and gynecomastia. He reported micropenis as a concern at the age of 13.5 years. His hormone profile revealed high levels of serum 17-hydroxyprogesterone, progesterone, and pregnenolone. In this case with a 46 XY karyotype, suspicions arose regarding Cytochrome P450 oxidoreductase deficiency due to ambiguous genitalia and an atypical hormone profile. Analysis unveiled two distinct homozygous and pathogenic variants in the CYP21A2 and CYP17A1 genes. Notably, mineralocorticoid precursors escalated, while cortisol and sex steroid precursors decreased during the high (250 mcg) dose ACTH stimulation test. The mutation c.1169C > G (p.Thr390Arg) in CYP17A1, which is the second documented case in literature, stands out due to its unique set of accompanying features. Mutations occurring in CYP21A2 and CYP17A1 result in complete or partial enzyme deficiencies, and the detection of homozygous mutations in two different enzyme systems within the steroidogenic pathway is noteworthy.

Evaluation of the effect of obesity, dietary glycemic index and metabolic profiles on the cardiovascular risk in children with classical phenylketonuria.

OBJECTIVES: To compare the glycemic index(GI),obesity,echocardiographic,and arterial stiffness measurements with the healthy control group to evaluate the cardiovascular risk of pediatric classical phenylketonuria(PKU). METHODS: The study was a prospective observational,involving 104 pediatric volunteers between 2019 and 2020.Two groups were formed:the PKU patient group and the healthy control group.These two groups were further divided into three subgroups:obese,overweight,and normal weight.The patients' anthropometric measurements,body fat analysis,biochemical analysis, GI and glycemic load(GL),arterial stiffness measurements,and echocardiographic findings were recorded. RESULTS: The PKU patient group's glucose,total cholesterol,LDL,and HDL values were significantly lower than the healthy control group(p = 0.010 for glucose and p = 0.001 for total cholesterol,LDL and HDL).Triglyceride levels were higher in the PKU patient group than in the healthy controls(109.6 vs. 76.7 mg/dl,p = 0.001). GI and GL were significantly lower in the PKU patient group than in the healthy control group(GI 453 vs. 392.9,p = 0.017 and GL 101.1 vs. 85.5,p = 0.036).Left ventricular mass(LVM)-z-score and LVM index were significantly higher in the PKU group than in the healthy control group(LVM z-score 0.9 vs. 0.5,p = 0.014 and LVM index 38.9 vs. 32.7 g/m2.7,p = 0.001). A moderately statistically significant positive correlation was found between the mean phenylalanine(phe) value and pulse wave velocity(PWV) among the PKU patient groups(R: 0.477,p < 0.001).A moderately statistically significant positive correlation was also found between waist circumference and PWV in the PKU patient group(R:0.541, p < 0.001). CONCLUSIONS: Our study found that close follow-up of phe levels and PWV is more critical than obesity, GI, and GL in the cardiovascular evaluation of classical PKU patients.A large number of multicenter pediatric studies are needed in this area.

Neonatal Diabetes, Congenital Hypothyroidism, and Congenital Glaucoma Coexistence: A Case of GLIS3 Mutation

Neonatal diabetes and congenital hypothyroidism (CH) syndrome is a rare condition caused by homozygous or compound heterozygous mutations in the GLIS3 gene. Small for gestational age, congenital glaucoma, polycystic kidney disease, cholestatic hepatic fibrosis, pancreatic exocrine insufficiency, developmental delay, dysmorphic facial features, sensorineural deafness, osteopenia, and skeletal anomalies are other accompanying phenotypic features in the 22 cases described so far. We present a male patient with neonatal diabetes, CH, congenital glaucoma, developmental delay, and facial dysmorphism. During the patient's 17-year follow-up, no signs of exocrine pancreatic insufficiency, liver and kidney diseases, deafness, osteopenia, and bone fracture were observed. A homozygous exon 10-11 deletion was detected in the GLIS3 gene. We report one of the oldest surviving GLIS3 mutation case with main findings of neonatal diabetes and CH syndrome to contribute to the characterization of the genotypic and phenotypic spectra of the syndrome.

Identifying the effects of excess weight, metabolic syndrome and insulin resistance on liver stiffness using ultrasound elastography in children.

BACKGROUND: Metabolic syndrome (MetS) and insulin resistance (IR) are known predictors of nonalcoholic fatty liver disease (NAFLD) which is one of the significant comorbidities of obesity. Obese children with MetS and IR are reported to be more likely to have advanced liver fibrosis compared to those without MetS or IR. The aim of this study is to determine the effects of excess weight, MetS and IR on liver fibrosis assessing liver stiffness in children using ultrasound elastography and compare gray scale ultrasonographic findings of hepatic steatosis (HS) with liver fibrosis. METHODS: The study group involved 131 overweight/obese children. The control group involved 50 healthy lean children. Groups were adjusted according to body mass index (BMI) and BMI-standard deviation scores (SDS). Liver stiffness measurements which are expressed by shear wave velocity (SWV) were performed for each individual. The study group was further subgrouped as children with MetS and without MetS, with IR and without IR. RESULTS: The mean SWV of liver was 1,07 ± 0,12 m/s in the control group and 1,15 ± 0,51 m/s in the study group. The difference was significant (p=0,047). SWV of liver was weakly correlated with age, BMI, BMI-SDS, Homeostatic Model Assessment-Insulin Resistance and high-density lipoprotein cholesterol. The mean SWV of the liver in the study group for children without MetS was 1,1 ± 0,44 m/s, with MetS was 1,23 ± 0,70 m/s. The difference was not significant (p=0,719). The mean SWV of the liver in the study group for children without IR was 1,02 ± 0,29 m/s, with IR was 1,24 ± 0,61 m/s. The difference was not significant (p=0,101). In multivariate regression analysis, the only independent factor affecting liver stiffness was BMI-SDS (OR:2,584, 95% CI: 1,255- 5,318, p=0,010). CONCLUSIONS: Obesity itself, regardless of MetS or IR seems to be the major problem affecting liver stiffness in this study. However, large scale longitudinal studies might clarify this issue.

The effect of the COVID-19 pandemic on metabolic control in children with type 1 diabetes: a single-center experience.

OBJECTIVES: Coronavirus disease 2019 has caused a major epidemic worldwide, and lockdowns became necessary in all countries to prevent its spread. This study aimed to evaluate the effects of staying-at-home practices on the metabolic control of children and adolescents with type 1 diabetes during the pandemic period. MATERIALS AND METHODS: Eighty-nine patients younger than 18 years old who were diagnosed with type 1 diabetes at least one year before the declaration of the pandemic were included in the study. The last visit data of the patients before and after the declaration of the pandemic, and the frequency of presentation of diabetes-related emergencies from one year after diagnosis of type 1 diabetes to the declaration of the pandemic, and from the declaration of the pandemic to the last visit after the pandemic declaration were compared. RESULTS: The total number of patients was 89, and 48 (53.9%) were boys. The mean (± standard deviation [SD]) age at diagnosis was 8.4 ± 3.7 years (boys 7.9 ± 3.6 years; girls 8.9 ± 3.9 years). There was no statistically significant difference when the SD values of the anthropometric measurements, and the glycosylated hemoglobin (HbA1c) and lipid profile tests were compared. However, the frequency of admission to the emergency service related to diabetes was significantly different. CONCLUSIONS: Although the pandemic did not significantly affect the metabolic and glycemic controls of the children with type 1 diabetes included in this study, an increase in the frequency of diabetes-related emergency admissions was noted.

Pathogenic variants in RNPC3 are associated with hypopituitarism and primary ovarian insufficiency.

PURPOSE: We aimed to investigate the molecular basis underlying a novel phenotype including hypopituitarism associated with primary ovarian insufficiency. METHODS: We used next-generation sequencing to identify variants in all pedigrees. Expression of Rnpc3/RNPC3 was analyzed by in situ hybridization on murine/human embryonic sections. CRISPR/Cas9 was used to generate mice carrying the p.Leu483Phe pathogenic variant in the conserved murine Rnpc3 RRM2 domain. RESULTS: We described 15 patients from 9 pedigrees with biallelic pathogenic variants in RNPC3, encoding a specific protein component of the minor spliceosome, which is associated with a hypopituitary phenotype, including severe growth hormone (GH) deficiency, hypoprolactinemia, variable thyrotropin (also known as thyroid-stimulating hormone) deficiency, and anterior pituitary hypoplasia. Primary ovarian insufficiency was diagnosed in 8 of 9 affected females, whereas males had normal gonadal function. In addition, 2 affected males displayed normal growth when off GH treatment despite severe biochemical GH deficiency. In both mouse and human embryos, Rnpc3/RNPC3 was expressed in the developing forebrain, including the hypothalamus and Rathke's pouch. Female Rnpc3 mutant mice displayed a reduction in pituitary GH content but with no reproductive impairment in young mice. Male mice exhibited no obvious phenotype. CONCLUSION: Our findings suggest novel insights into the role of RNPC3 in female-specific gonadal function and emphasize a critical role for the minor spliceosome in pituitary and ovarian development and function.

Evaluation of micronutrient levels in children and adolescents with obesity and their correlation with the components of metabolic syndrome.

BACKGROUND: Obesity is a significant public health problem worldwide. Vitamin deficiencies, developing due to monotype nutrition, are more likely to be observed in patients than healthy children. The present study evaluates vitamin and micronutrient levels in children and adolescents with obesity and metabolic syndrome compared to healthy controls. METHODS: The study included 73 patients with obesity, 64 patients with metabolic syndrome and 71 healthy children (control group) aged 10 to 16 years. Physical examinations were performed, and waist circumference and systolic blood pressure measurements were recorded. Fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, insulin, vitamin A, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, folic acid and free carnitine levels were analyzed. The homeostatic model of assessment-insulin resistance (HOMA-IR) index was calculated and recorded. RESULTS: The mean age of all patients was 11.9±2.6 years. The serum insulin level and HOMA-IR index were found to be significantly higher in the obesity and metabolic syndrome groups. No significant difference was found between the groups in terms of vitamin A, vitamin B6 and free carnitine levels. Significantly decreased vitamin E, vitamin B2, vitamin B12 and folic acid and increased vitamin B1 levels were observed in the obesity and metabolic syndrome groups. CONCLUSIONS: Compared to healthy children, children with obesity and metabolic syndrome may have varying degrees of micronutrient and vitamin deficiency due to poor and unbalanced eating habits. These deficiencies should also be considered in the treatment and follow-up of obesity and metabolic syndrome.

Endocrine Disruptors and Polycystic Ovary Syndrome: Phthalates

Objective: We aimed to investigate a possible role of the endocrine disruptors phthalates, di-2-ethylhexyl phthalate (DEHP) and mono (2-ethylhexyl) phthalate (MEHP), in polycystic ovary syndrome (PCOS) aetiopathogenesis. We also wished to evaluate the relationship between phthalates and metabolic disturbances in adolescents with PCOS. Methods: A total of 124 adolescents were included. Serum MEHP and DEHP levels were determined by high-performance liquid chromatography. Insulin resistance was evaluated using homeostasis model assessment-insulin resistance, quantitative Insulin Sensitivity Check Index, fasting glucose/insulin ratio, Matsuda index, and total insulin levels during oral glucose tolerance test. Participants were further subdivided into lean and obese subgroups according to body mass index (BMI). Results: Sixty-three PCOS and 61 controls, (mean age 15.2±1.5; range: 13-19 years) were enrolled. Serum DEHP and MEHP concentrations were not significantly different between PCOS and control groups. The mean (95% confidence interval) values of DEHP and MEHP were 2.62 (2.50-2.75) µg/mL vs 2.71 (2.52-2.90) µg/mL and 0.23 (0.19-0.29) µg/mL vs 0.36 (0.18-0.54) µg/mL in PCOS and the control groups respectively, p>0.05. Correlation analysis, adjusted for BMI, showed that both phthalates significantly correlated with insulin resistance indices and serum triglycerides in adolescents with PCOS. Conclusion: Serum DEHP and MEHP concentrations were not different between adolescents with or without PCOS. However, these phthalates are associated with metabolic disturbances such as dyslipidemia and insulin resistance, independently of obesity, in girls with PCOS.

Neutropenia and Increased Mean Corpuscular Volume (MCV) With Abnormal Neurologic Findings: A Case of Cobalamin D Deficiency.

BACKGROUND: Disorders of intracellular cobalamin (Cbl) metabolism are classified from A to J according to biochemical phenotype, and genetic and complementation analyses. CblD-deficient patients present with developmental, hematologic, neurologic, and metabolic findings. CLINICAL OBSERVATION: An 11-year-old boy presented with neutropenia, increased mean corpuscular volume, psychomotor retardation, and seizures. His plasma total homocysteine and urinary methylmalonic acid levels were elevated, and a homozygous nonsense mutation [p. R250X (c.748C>T] leading to premature termination of translation was identified in the MMADHC gene, which was compatible with CblD defect. CONCLUSION: In the presence of increased mean corpuscular volume and other hematologic manifestations, such as leukopenia, thrombocytopenia, and megaloblastic anemia, with severe nonspecific or mild neurologic symptoms, Cbl synthesis defects should be considered.

Comparison of Treatment Regimens in Management of Severe Hypercalcemia Due to Vitamin D Intoxication in Children

Objective: No large study has been conducted to date to compare the effectiveness of prednisolone, alendronate and pamidronate as first-line treatment in children with hypercalcemia due to vitamin D intoxication. The aim was to perform a multicenter, retrospective study assessing clinical characteristics and treatment results. Methods: A standard questionnaire was uploaded to an online national database system to collect data on children with hypercalcemia (serum calcium level >10.5 mg/dL) due to vitamin D intoxication [serum 25-hydroxyvitamin D (25(OH)D) level >150 ng/mL] who were treated in pediatric endocrinology clinics. Results: Seventy-four children [median (range) age 1.06 (0.65-1.60) years, 45 males (61%) from 11 centers] were included. High-dose vitamin D intake was evident in 77% of the cases. At diagnosis, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D and parathyroid hormone concentrations were 15±3.2 mg/dL, 5.2±1.2 mg/dL, 268±132 IU/L, 322 (236-454) ng/mL, and 5.5 (3-10.5) pg/mL, respectively. Calcium levels showed moderate correlation with 25(OH)D levels (rs=0.402, p<0.001). Patients were designated into five groups according to the initial specific treatment regimens (hydration-only, prednisolone, alendronate, pamidronate, and combination). Need for another type of specific drug treatment was higher in children who initially received prednisolone (p<0.001). Recurrence rate of hypercalcemia was significantly lower in children who were treated with pamidronate (p=0.02). Conclusion: Prednisolone is less effective in the treatment of children with severe hypercalcaemia secondary to vitamin D intoxication and timely implementation of other treatment regimens should be considered.

The Incidence of Cystic Fibrosis in the Central Region of Anatolia in Turkey Between 2015 and 2016

Background: Cystic fibrosis is the most common metabolic chronic disease among European Caucasian children. Cystic fibrosis incidence in Northern Europeans countries is approximately 1 in 3000 births while the worldwide prevalence varies considerably. Aims: To determine the incidence of cystic fibrosis in the central region of Anatolia in Turkey using the newborn screening program data. Study Design: Cross-sectional study Methods: We used the records of the newborn screening program which is implemented by the Konya and Kayseri Provincial Health Directories. Between January 2015 and December 2016, there were a total of 119006 live births in Konya and Kayseri. The newborn screening test was applied to all these babies. Results: During this period, there were 22 live born babies diagnosed with cystic fibrosis in Konya with an incidence of 2.9 per 10000 live births and 13 live born babies diagnosed with cystic fibrosis in Kayseri with an incidence of 2.8 per 10000 live births. In genetic of 30 patients, fifteen patients were homozygous, and 15 patients were a compound heterozygote. Twenty-one different gene variants were detected and the most common mutation was F508del (17/30). Conclusion: We found the incidence of cystic fibrosis in central Anatolia similar to northern European countries.

Arthropathy-like findings and a carpal tunnel syndrome as the presenting features of Scheie syndrome: Three cases from the same family.

Gökay S, Kardas F, Kendirci M, Sözeri B. Arthropathy-like findings and a carpal tunnel syndrome as the presenting features of Scheie syndrome: Three cases from the same family. Turk J Pediatr 2018; 60: 344-347. Mucopolysaccharidosis (MPS) type I is a rare autosomal recessive disease caused by a deficiency of the lysosomal enzyme α-L-iduronidase. MPS I is divided into three subtypes based on the severity of symptoms: Hurler, Hurler-Scheie, and Scheie syndrome (severe, intermediate, and mild forms, respectively). Musculoskeletal involvement may be the only presenting sign in the patients with Scheie syndrome. We have reviewed three cases with prominent features of carpal tunnel syndrome (CTS) at the onset of their disease. Diagnosis was delayed in almost all cases (range 16-19 years). During one year of follow-up period, alleviations of the pain in the hands of patients were observed after enzyme replacement therapy. MPS type I should be considered in the differential diagnosis of the patients with CTS in the first and second decades of life, particularly with stiffness of the fingers and difficulty using the hands without an inflammatory component. An increased awareness of the disease may contribute to more accurate diagnosis, and patients may benefit from early intervention.

Menstrual Characteristics and Related Problems in 9- to 18-Year-Old Turkish School Girls.

STUDY OBJECTIVE: To determine the cross-sectional characteristics of menstruating girls, dysmenorrhea, and the frequencies of related problems. DESIGN: Descriptive, cross-sectional study. SETTING: Randomly selected primary, junior, and high schools in the city center of Kayseri. PARTICIPANTS: Two thousand female adolescents of ages between 9 and 18 years. MAIN OUTCOME MEASURES: We used a questionnaire addressing the epidemiological characteristics of menstruation, such as age at menarche, duration of menstrual intervals, average days of bleeding, and any menstrual problems and their frequencies. RESULTS: This study consists of a sufficient number of participants from all age groups. Of the participant (n = 2000) girls, 63.7% (n = 1274) had started menstruating. The mean age at menarche was 12.74 (±1.03) years. With a prevalence of 84.8% (n = 1080), dysmenorrhea was the most prevalent menstrual problem and the average pain score was 5.87 (±2.45). Of the menstruating girls, 34% (n = 439) used painkillers, the most commonly used was acetaminophen; during their period the prevalence of nonmedical methods to relieve pain was 35.2%; the rate of seeking medical help for dysmenorrhea was 9.3% (n = 119). In menstruating participants, 90.8% discussed their menstrual problems with their mothers. The rate of school absenteeism in menstruating girls was 15.9% in general and 18% in those with dysmenorrhea. CONCLUSION: Problems related to menstruation are common in adolescents and these problems affect their social life. In adolescent girls, the most common menstrual problem is dysmenorrhea and it affects school performance and attendance. Girls with menstrual problems showed a low rate of seeking medical help.

ROHHAD Syndrome, a Rare Cause of Hypothalamic Obesity: Report of Two Cases

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disease that is difficult to diagnosis and distinguish from genetic obesity syndromes. The underlying causes of the disease have not been fully explained. Hypothalamic dysfunction causes endocrine problems, respiratory dysfunction and autonomic alterations. Currently there are around 80 reported patients although this is likely due to underdiagnosis due to lack of recognition. We present two female patients suspected of ROHHAD due to weight gain starting in early childhood. Clinical and biochemical findings such as respiratory and circulatory dysfunction, hypothalamic hypernatremia, central hypothyrodism, hyperprolactinemia and central early puberty in these patients matched the criteria for ROHHAD syndrome. ROHHAD syndrome should be considered in the differential diagnosis of monogenic obesity.

Glutaric Acidemia Type 1: A Case of Infantile Stroke.

BACKGROUND: Glutaric acidemia Type 1 (GA-1) is an autosomal recessively inherited metabolic disorder which is associated with GCDH gene mutations which alters the glutaryl-CoA dehydrogenase, an enzyme playing role in the catabolic pathways of the amino acids lysine, hydroxylysine, and tryptophan. Clinical findings are often encephalopathic crises, dystonia, and extrapyramidal symptoms. CASE REPORT: A 9-month-old male infant referred to our department with focal tonic-clonic seizures during rotavirus infection and acute infarcts in MRI. Clinical manifestation, MRI findings, and metabolic investigations directed thoughts towards GA-I. Molecular genetic testing revealed a homozygous c.572T>C (p.M191T) mutation in GCDH gene which confirmed the diagnosis. Application of protein restricted diet, carnitine and riboflavin supplementations prevented the progression of Magnetic Resonance Imaging (MRI) and clinical pathologic findings during the 1 year of follow-up period. CONCLUSION: This case is of great importance since it shows possibility of infantile stroke in GA-1, significance of early diagnosis and phenotypic variability of disease.

Evaluation of vitamin D prophylaxis in 3-36-month-old infants and children.

BACKGROUND: Vitamin D (VD) deficiency (VDD) is still a population-based health problem that affects people at different ages. The aim of this study was to evaluate VD prophylaxis for the prevention of VDD in (3-36)-month-old infants and children. METHODS: Infants and children aged between 3 and 36 months, with different etiologies, admitted to outpatient and inpatient clinics from October 2010 to October 2011 at the Children's Hospital of Erciyes University, were enrolled for the study. Their VD intake (if used; time of initiation, dosage and compliance) and nutritional status (breast-fed, formula or complementary fed) were noted. In order to study seasonal VD changes, the levels of serum calcium, phosphorus and magnesium, alkaline phosphatase activity (PLA), plasma parathyroid hormone (PTH) and 25 hydroxyvitamin 25(OH)D levels were measured at the beginning of VD supplementation during the four seasons. RESULTS: A total of 316 subjects were enrolled in the study, consisting of 202 (63.9%) outpatient and 114 (26.1%) inpatient groups. From these subjects, 304 (96.2%) were supplemented with VD; whereas 12 (3.8%) were not. Out of the subjects supplemented with VD, 237 (75%) initiated VD after the second week of life, 267 (87.8%) were given three drops of VD daily and 209 (66.1%) had taken VD regularly. The plasma 25(OH)D levels were found to be lower in the inpatient group than the outpatient group (29.35 ng/mL and 34.35 ng/mL, respectively). The plasma 25(OH)D levels were lower during the spring and winter. VDD and VD insufficiency (VDI) was found in 31 (9.8%) and 30 (9.5%) subjects, respectively. CONCLUSIONS: The plasma 25(OH)D levels were lower in inpatient and breast-fed only subjects and in winter and spring. The national VD augmentation program seems to be beneficial for the prevention of VDD, but VDD/VDI seems to still be an important health problem.

Urinary levels of pyridinoline and deoxypyridinoline and bone mineral density in children with type 1 diabetes mellitus.

OBJECTIVE: There is still controversy over the impact of diabetes mellitus (DM) on bone mass in children. Pyridinoline (Pyr) and deoxypyridinoline (DPyr), which stabilize the collagen chains within the extracellular matrix, are known as specific bone turnover markers. The aim of this study was to investigate the relationship between urinary Pyr and DPyr excretions and bone mineral density (BMD) in children with type 1 DM. METHODS: Serum levels of Ca, phosphorus (P), magnesium (Mg), and parathormone (PTH), alkaline phosphatase (ALP) activity, and urinary excretions of Pyr and DPyr were evaluated in 50 diabetic and 130 healthy control subjects aged between 7 and 15 years. The BMD was measured using DEXA at the lumbar vertebrae 2-4. RESULTS: Serum levels of Ca, P and PTH, and BMD were similar between the two groups (p > 0.05). The serum ALP activity was significantly higher in diabetics than in healthy subjects (257.7 ± 86.5 vs. 188.2 ± 61.8, p < 0.05, respectively). Both urinary Pyr and DPyr excretions were significantly higher in diabetic subjects compared to control subjects (127.4 ± 95.5 vs. 88.7 ± 63.7, p < 0.05, respectively, and 23.6 ± 12.7 vs. 17.2 ± 9.6, p < 0.05, respectively). The urinary excretions of Pyr and DPyr were similar in male and female subjects within both groups. CONCLUSION: The urinary excretions of Pyr and DPyr are higher in diabetic subjects than in healthy controls, suggesting the presence of increased bone turnover in diabetic patients, but we could not observe any negative effect of childhood diabetes on BMD. These results may suggest that diabetic patients are at risk for a decreased peak bone mass.

The outcome of seven patients with hereditary tyrosinemia type 1.

BACKGROUND: Hereditary tyrosinemia type 1 (HT1) is a rare, inborn error of tyrosine metabolism. It is a fatal disorder without treatment. Early treatment may prevent acute liver failure, renal dysfunction, liver cirrhosis, hepatocellular carcinoma (HCC) and improves survival. The aim of the present study is to describe the clinical, biochemical, imaging and follow-up of seven patients with HT1 and to define the consequences of the late and interrupted treatment. METHODS: A retrospective study was carried out with seven HT1 patients. RESULTS: The median age at onset of clinical symptoms was 11.2 months (range, 3-28 months) and the median age at diagnosis was 22 months (range, 6-58 months). Liver enzymes and coagulation parameters were back to normal in all symptomatic patients in about 2 weeks. Alfa-fetoprotein (AFP) levels were normalized within the first year of therapy. Hypoechoic nodule formation was detected in two of the seven patients despite drug treatment without an increase of AFP and any dysplastic changes in the biopsies. One patient died due to metastatic HCC because of the late diagnosis and the poor compliance of the follow-up. CONCLUSIONS: This study showed once again that adherence to the treatment and a follow-up schedule of the patients are very important. Also it should not be forgotten that nodule formation can occur despite nitisinone treatment without an increase of AFP. Despite nitisinone treatment, HT1 patients still carry the risk of HCC. HCC must be detected before metastasis to other organs otherwise, patients may lose the chance for liver transplantation.

Plasma glutamine and cystine are decreased and negatively correlated with endomysial antibody in children with celiac disease.

BACKGROUND AND OBJECTIVES: Glutamine is a nonessential amino acid which improves intestinal mucosal regeneration and absorption. Glutathione is a vital molecule for antioxidant reactions and is synthesized from cystine. The first aim of the study is to measure the plasma glutamine and cystine in children with celiac disease (CD) and compare them with controls. The second aim of this study is to investigate whether these amino acids are correlated with endomysial antibody (EMA) or not. METHODS AND STUDY DESIGN: Fifty children with CD were compared to 50 healthy, age, and sex matched normal children as control. Plasma glutamine and cystine levels of the children were measured by using tandem mass spectrometry. RESULTS: Plasma glutamine (808 vs 870 µmol/L) and cystine (19 vs 48.5 µmol/L) were significantly lower in the celiac group than the controls (p<0.05). The levels of plasma glutamine (797 vs 928 µmol/L, n=42) and cystine (18 vs 31.5 µmol/L, n=8) were lower (p<0.05) in the EMA-positive than the EMA-negative celiac patients. We could not find any statistically significance between EMA-negative celiac patients and controls for the plasma glutamine (928 vs 870 µmol/L) and cystine (31.5 vs 48.5 µmol/L) (p>0.05). Serum EMA was negatively correlated with plasma cystine (r=-0,321, p=0.023), glutamine (r=-0.413, p=0.003). CONCLUSIONS: Our study indicated that plasma glutamine and cystine were significantly lower in the celiac children than the controls. Also, these amino acids were negatively correlated with EMA.