Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome - a case report and literature review.

MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) is a genetically determined disease caused by mutations in mitochondrial DNA. We present a girl who was suspected of MELAS syndrome during the diagnostic evaluation of short stature. The patient suffered from symptoms potentially indicating mitochondrial disease, such as muscular weakness, cranial nerve VI palsy, headaches, retinitis pigmentosa, sensory-neural hearing loss, and elevated lactic acid. T2-weighted brain MRI showed hyperintense lesions in the white matter. Muscular biopsy revealed ragged red fibres. Genetic evaluation did not detect the most common mutations in the MT-TL1 gene and MT-ND5 gene. Endocrine tests led to the confirmation of growth hormone deficiency, and so replacement treatment was started. After 1 year of recombinant growth hormone therapy the patient was diagnosed with diabetes. At the age of 14 years the LH-RH test showed prepubertal values. Endocrine disorders may be one of the first manifestations of MELAS syndrome. In differential diagnosis of short stature, less common causes, such as mitochondrial diseases, should be taken into consideration.

Porto-systemic shunt - a rare cause of hyperandrogenism in children. Two case reports and review of literature.

Objectives The main cause of hyperandrogenism in children is congenital adrenal hyperplasia, adrenal and gonadal tumors, polycystic ovary syndrome (PCOs) and Cushing's disease. In the last 20 years several descriptions of girls with hyperandrogenism and venous porto-systemic shunts appeared in literature. Case presentation First case is an eleven and a half-year-old girl, was admitted to Department of Endocrinology because of symptoms of hyperandrogenism. Laboratory tests revealed high serum testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS). The ammonia concentration was also increased. In the abdominal angio-CT scans persistent umbilical vein which connected portal and femoral vein was found. The second case was a seven-year-old boy with symptoms of precocious puberty. Blood tests also revealed high concentration of testosterone, androstenedione, DHEAS and ammonia. Imaging studies showed persistent ductus venosus. Conclusion Although pathophysiological relation is not clear, porto-systemic shunts should be considered as a cause of hyperandrogenism of unknown origin in children.

Detection of new potentially pathogenic mutations in two patients with primary pigmented nodular adrenocortical disease (PPNAD) - case reports with literature review.

INTRODUCTION: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare form of ACTH-independent Cushing's syndrome (CS). Half of patients with PPNAD are sporadic cases and the other half familial. MATERIAL AND METHODS: We present two patients with PPNAD confirmed by genetic analysis. RESULTS: In both patients there were no abnormal findings on diagnostic imaging of both adrenals and heart. Patients underwent bilateral two-stage adrenalectomy. Histopathological examination confirmed PPNAD. Genetic testing showed the following mutations in the PRKAR1A gene coding for the regulatory subunit type 1A of the protein kinase A enzyme: c.125dupG (patient 1) and c.15dupT (patient 2). Both these defects lead to inactivation of the PRKAR1A protein and are consequently causative of PPNAD in these patients. CONCLUSIONS: The novel mutations presented in this article are considered to be pathogenic for PPNAD.

Pediatric patient with hyperketotic hypoglycemia diagnosed with glycogen synthase deficiency due to the novel homozygous mutation in GYS2.

BACKGROUND: Glycogen synthase deficiency (glycogen storage disease 0 - GSD 0) caused by mutations in the GYS2 gene is characterized by a lack of glycogen synthesis in the liver. It is a rare condition of disturbed glycogen homeostasis in the liver with less than 30 cases reported in the literature so far. CASE REPORT: We report a 9 year old boy diagnosed with GSD 0 due to the newly identified, highly pathogenic homozygous mutation: NM_021957.3:p.Phe574Leu/c.1720T > C in ex. 14. A random, asymptomatic hypoglycemia with ketonuria was found in this patient at the age of 7. His developmental parameters were within normal ranges. Oral glucose tolerance test showed normal baseline blood levels of glucose, insulin and lactate, and their increase following glucose intake. Eight-hour fasting plasma glucose test, revealed glucose blood level of 34 mg/dl with no clinical symptoms. The results of these tests suggested GSD 0. Molecular analysis of the GYS2 gene was not feasible, but this particular gene was included in the panel of hypoglycemia of whole exome sequencing (WES) which was at our disposal.