Homozygous pArg610del Mutation Unusually Associated With Severe Delay of Growth in 2 Acid Sphingomyelinase Deficiency-affected Sibs.

BACKGROUND: Typically, patients with Acid Sphingomyelinase Deficiency (ASMD) because of p.Arg610del mutation, have mild phenotype with normal linear growth. OBSERVATION: We reported the case of 2 Tunisian brothers who have been referred for splenomegaly, polyadenopathies, pubertal, and growth delay. Molecular testing of SMPD1 gene revealed the presence of a homozygous p.Arg610del mutation. Lysosphingomyelin and its isoform-509 were both increased confirming ASMD for both cases. Growth hormone deficiency was highly suspected but growth hormone response after stimulating tests was acceptable for both patients. CONCLUSIONS: There is no correlation between phenotype-genotype in case of p.Arg610del mutation that could be associated to a severe delay of growth.

Potential role of liver enzyme levels as predictive markers of glucose metabolism disorders in a Tunisian population.

The relationship between liver enzymes and T2D risk is inconclusive. We aimed to evaluate the association between liver markers and risk of carbohydrate metabolism disorders, as well as their discriminatory power, for T2D prediction. This cross-sectional study enrolled 216 participants classified as normoglycemic, prediabetic, newly diagnosed diabetics, and diagnosed diabetics. All participants underwent anthropometric and biochemical measurements. The relationship between hepatic enzymes and glucose metabolism markers was evaluated by analyses of covariance. The associations between liver enzymes and incident carbohydrate metabolism disorders were analyzed through logistic regression and their discriminatory capacity to predict T2D by ROC analysis. High AP, ALT, γGT, and AST levels were independently related to decreased insulin sensitivity. Interestingly, a higher AP level was significantly associated with an increased risk of prediabetes (p = 0.017), newly diagnosed diabetes (p = 0.004), and T2D (p = 0.007). An elevated γGT level was an independent risk factor for T2D (p = 0.032) and undiagnosed T2D (p = 0.010) in prediabetic and normoglycemic subjects, respectively. In ROC analysis, AP was a powerful predictor of incident diabetes and significantly improved T2D prediction. Liver enzymes within the normal range, specifically AP levels, are associated with increased risk of carbohydrate metabolism disorders and significantly improved T2D prediction.

Sensitivity to pain in autistic spectrum disorders: Its links with self-gressivity.

OBJECTIVES: To investigate the link between pain sensitivity in autism spectrum disorders (ASD) and self-aggressive behavior. METHODS: we performed a cross-sectional study which involved 50 children fulfilling DSM-V criteria for ASD; confirmed by the Autism Diagnostic Interview Revised. The severity of autism was determined using the Childhood Autism Rating Scale (CARS).The psycho-educational profile (PEP-R) was used to assess the age of development and perception.  Sensitivity to pain was assessed with item IX of the CARS. Self-aggressive behavior was assessed by the Behavior Problems Inventory. RESULTS: Pain sensitivity was lowered in 40% and elevated in 4% of children. In the univariate analysis, no statistically significant association was found between normal sensitivity or hyper sensitivity to pain and the presence of auto-aggressiveness. A significant association was found between the presence of hypo-sensitivity to pain and the following variables: auto-aggression (p = 0.007, OR = 5.8, 95% CI = 1.5-21) , frequency of self-aggression (p = 0.001), intensity of self-aggression (p = 0.05), location of auto-aggressiveness at head and (P = 0.007, OR = 7.6, 95% CI = 1.8-14), higher score at CARS, and lower perception score at PEP-R (p = 0.012). Multiple-varied analysis identified risk factors for hypo-sensitivity to pain: lower perceptual score (p = 0.003, adjusted OR = 4.3, 95% CI = 1.9-54) and location of self-aggression at head and hands (p = 0.001, adjusted OR = 1.09, 95% CI = 1.02-1.09). CONCLUSION: It would be interesting to develop tools allowing a fine and precise evaluation of the painful sensation.

Metabolic syndrome and physical activity measured by pedometer among adolescents.

AIM: To describe the prevalence of metabolic syndrome and to study the association of physical activity measured by pedometer with the metabolic syndrome components, in a sample of overweight and obese adolescents from Sfax City. METHODS: This study concerned 51 obese and overweight adolescents (28 girls and 23 boys), between the ages of 15 and 18 years, recruited by the unit of obesity and metabolic syndrome department of endocrinology, Hedi Chaker Hospital, University of Sfax, between december 2012 and october 2013. Metabolic syndrome was defined with the International Diabetes Federation (IDF) criteria. Physical activity was monitored with pedometer (Digi-Walker SW-200; Yamax Co, Tokyo, Japan). RESULTS: The frequency of metabolic syndrome was 21.6%. It was significantly higher in obese (25%) than in overweight (15,81%) adolescents (p=0.04). The most common component, associated with abdominal obesity, was hypoHDLemia observed in 58.8 % of the sample. The average steps / day measured by pedometer was significantly higher in subjects without metabolic syndrome than with (9648, 25±2297, 726 vs 7365, 91±1505, 65 steps/day; p=0, 03). Pedometer determined steps/day was inversely correlated with waist circumference (P<0.05), blood pressure (P<0.05) and triglycerides (P<0.05). CONCLUSION: Metabolic syndrome is prevalent in our young population. A more physically active lifestyle appears to be associated with lower probability of metabolic syndrome.

Fahr's syndrome in Southern Tunisia: A broad spectrum of clinical and etiological features.

AIM: We describe the clinical and etiological profile of patients with Fahr's syndrome (FS). METHODS: Charts of sixteen patients diagnosed with FS between 1999 and 2014 were retrospectively assessed. RESULTS:   The mean age at diagnosis was 44.68 years (11-67 years). The most main presenting neurological features were seizures in 6 cases, headaches in 5 cases and parkinson's syndrome in 3 cases. Psychiatric disorders were observed in 2 patients including memory loss and iritability. Hypocalcemia clinical features were observed in 7 cases. The mean value of hypocalcemia was 1.69 mmol/l. Etiologies included idiopathic hypoparathyroidism in 4 patients, pseudohypoparathyroidism in 5 cases, secondary hypoparathyroidism, isolated hypovitaminosis D and cerebral radiotherapy in one case for each and Fahr's disease in 4 patients.  Oral calcium and vitamin D substitution were started in patients with parathyroid disturbances with favorable outcome. CONCLUSION: In this report, we propose to discuss the clinical manifestations of FS, its etiologies especially parathyroid disturbances and its therapeutic modalities.

The Reliability and Concurrent Validity of a Modified Version of the International Physical Activity Questionnaire for Adolescents (IPAQ-A) in Tunisian Overweight and Obese Youths.

OBJECTIVE: The aim of the present study was to assess the reliability and validity of an Arabic version of the International Physical Activity Questionnaire for Adolescents (IPAQ-A) modified for use in Tunisia among overweight and obese adolescents. SUBJECTS AND METHODS: Fifty-one voluntary healthy, overweight or obese adolescents (15-18 years old) participated in the study. Physical activity (PA) indicators derived from the modified self-administered IPAQ-A were compared with pedometer-recorded data of step counts. The test-retest reliability of the IPAQ-A was evaluated using intraclass correlation coefficients (ICC) and Kappa tests between the response of participants in the two interviews. Validity was assessed using Spearman's rank correlation coefficient between the scores of the IPAQ-A and the step count pedometer. RESULTS: ICC revealed that the reliability of IPAQ-A values was high and ranged from 0.73 to 0.95. IPAQ-A scores were also significantly related to pedometer step counts (r = 0.66, p < 0.001). Strong relationships were observed between pedometer step count data and the IPAQ-A data for vigorous PA (r = 0.57, p < 0.001) and walking (r = 0.61, p < 0.001). However, a weaker relationship for moderate PA was observed (r = 0.24, p < 0.05). CONCLUSIONS: The modified version of the IPAQ-A questionnaire demonstrated an acceptable reliability and validity when used to assess the levels and patterns of PA in overweight or obese Tunisian adolescents.

A novel mutation MT-COIII m.9267G>C and MT-COI m.5913G>A mutation in mitochondrial genes in a Tunisian family with maternally inherited diabetes and deafness (MIDD) associated with severe nephropathy.

Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia, maternal transmission and its association with a bilateral hearing impairment. Several studies reported mutations in mitochondrial genes as potentially pathogenic for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells. In the present report, we studied a Tunisian family with mitochondrial diabetes (MD) and deafness associated with nephropathy. The mutational analysis screening revealed the presence of a novel heteroplasmic mutation m.9276G>C in the mitochondrial COIII gene, detected in mtDNA extracted from leukocytes of a mother and her two daughters indicating that this mutation is maternally transmitted and suggest its implication in the observed phenotype. Bioinformatic tools showed that m.9267G>C mutation (p.A21P) is « deleterious ¼ and it can modify the function and the stability of the MT-COIII protein by affecting the assembly of mitochondrial COX subunits and the translocation of protons then reducing the activity of the respective OXPHOS complexes of ATP synthesis. The nonsynonymous mutation (p.A21P) has not been reported before, it is the first mutation described in the COXIII gene which is related to insulin dependent mitochondrial diabetes and deafness and could be specific to the Tunisian population. The m.9267G>C mutation was present with a nonsynonymous inherited mitochondrial homoplasmic variation MT-COI m.5913 G>A (D4N) responsible of high blood pressure, a clinical feature detected in all explored patients.

Segregation of S292F TPO gene mutation in three large Tunisian families with thyroid dyshormonogenesis: evidence of a founder effect.

UNLABELLED: We aimed to identify causal mutation(s) in 13 patients with thyroid dyshormonogenesis (TD) from three consanguineous Tunisian families. A 12-year clinical follow-up showed phenotypic variability ranging from the presence to the absence of goiter, sensorineural deafness, and mental retardation. Genetic analysis using microsatellite markers within two candidate genes (TPO and PDS) gave evidence of linkage with the TPO gene. Sequencing of its 17 exons and their flanking intron-exon junctions revealed the previously described c.875C>T (p.S292F) mutation in homozygous state. No additional mutations were found in either a 900 bp of the TPO gene promoter or PDS gene. In silico analysis showed that p.S292F mutation might reduce the catalytic cavity of the TPO which would restrict access of a potential substrate to the catalytic pocket. Using 4SNPs and one microsatellite marker in the TPO gene, an associated haplotype: G-C-G-G-214 was found, giving evidence of a founder mutation. CONCLUSION: This is the first description of a TD causing mutation in Tunisia and thus may help to develop a genetic screening protocol for congenital hypothyroidism in the studied region. Although structural modeling suggested a pathogenic effect of this mutation, functional studies are needed. Additional causing and/or modifier genes, together with late diagnosis could explain the clinical variability observed in our patients.

Metabolic Disorders During Prolactinomas.

The metabolic profile during prolactinoma may be subject to significant changes. We aimed to describe the different metabolic aspects in patients monitored for prolactinoma and to study the correlations between the size of the prolactinoma and the metabolic parameters. We conducted a retrospective, descriptive, and analytical study of 77 cases of prolactinomas collected and monitored at the endocrinology and diabetology department of the Hedi Chaker Hospital in Sfax between 2000 and 2017. Our patients were divided into three groups according to the size of their prolactinomas. Statistical correlations were sought between tumor size and clinical and biological parameters. The mean age of our patients was 38.3 ± 14.2 years. They were divided into 51 women (66.2%) and 26 men (33.7%). Pituitary tumor syndrome was the most common circumstance of discovery in our population (62.3%). The clinical examination revealed an average waist circumference of 95.71 cm. Android fat distribution was observed in 25 women (49%) and 12 men (46.1%). A statistically significant positive correlation was objectified between waist circumference and tumor size (r = 0.29 and P = 0.019). The average body mass index was 28.08 kg/m2. Obesity was noted in 56 cases (72.7%). Glucose tolerance disorders and hypertriglyceridemia were also more evident each time prolactinoma size increased in contrast to the level of high-density lipoprotein cholesterol which decreased with adenoma size. Our study highlighted the metabolic and hormonal repercussions of prolactinomas. Metabolic syndrome was more common in patients with larger prolactinoma. These results should guide the initial assessment and therapeutic management of prolactin adenomas.

A maternally inherited diabetes and deafness patient with the 12S rRNA m.1555A>G and the ND1 m.3308T>C mutations associated with multiple mitochondrial deletions.

Maternally inherited diabetes and deafness (MIDD) is a mitochondrial syndrome characterized by the onset of sensorineural hearing loss and diabetes in adults. Some patients may have other additional clinical features common in mitochondrial disorders such as pigmentary retinopathy, ptosis, cardiomyopathy, myopathy and renal affections. We report a 40-year-old Tunisian patient presenting maternally inherited type 2 diabetes and deafness (MIDD). A molecular genetic analysis was conducted in the patient and his twin sister, but no reported mutations in the tRNA(Leu(UUR)) and tRNA(Glu) genes were found, especially the two mitochondrial m.3243A>G and the m.14709T>C mutations in muscle and blood leukocytes. The results showed the presence of the mitochondrial NADH deshydrogenase 1 (ND1) homoplasmic m.3308T>C mutation the 2 tested tissues (blood leukocytes and skeletal muscle) of the proband and in the patient's sister blood leukocytes. In addition, we identified the mitochondrial 12S rRNA m.1555A>G mutation in muscle and blood leukocytes. The Long-range PCR amplification revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient's skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of MIDD in whom we detected the 12S rRNA m.1555A>G and the ND1 m.3308T>C mutations with mitochondrial multiple deletions.

A novel nonsense mutation in HSD17B3 gene in a Tunisian patient with sexual ambiguity.

INTRODUCTION: 17ß-hydroxysteroid dehydrogenase type 3 (HSD17B3) isoenzyme is present almost exclusively in the testes and converts delta 4 androstenedione to testosterone. Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46,XY Disorders of Sex Development (46,XY DSD). AIM: This study aimed to present the clinical and biochemical features of a Tunisian patient who presented a sexual ambiguity orienting to HSD17B3 deficiency and to search for a mutation in the HSD17B3 gene by DNA sequencing. METHODS: Polymerase chain reaction (PCR) amplification and subsequent sequencing of all the coding exons of HSD17B3 gene were performed on genomic DNA from the patient, her family, and 50 controls. RESULTS: Genetic mutation analysis of the HSD17B3 gene revealed the presence of a novel homozygous nonsense mutation in the exon 9 (c.618 C>A) leading to the substitution p.C206X. The mutation p.C206X in the coding exons supports the hypothesis of HSD17B3 deficiency in our patient. CONCLUSION: The patient described in this study represented a new case of a rare form of 46,XY DSD, associated to a novel gene mutation of HSD17B3 gene. The screening of this mutation is useful for confirming the diagnosis of HSD17B3 deficiency and for prenatal diagnosis.

Diagnosis and management of pituitary apoplexy: a Tunisian data.

BACKGROUND: Pituitary apoplexy (PA) is defined as the hemorrhage or the infraction of a pituitary adenoma. Aiming to determine the epidemiological, clinical, paraclinical characteristics as well as management and outcomes of PA in our population, we conducted this cross-sectional study. METHODS: This cross-sectional study was conducted at the Department of Endocrinology of Hedi chaker university hospital, Sfax. Data was collected from medical charts of patients with pituitary apoplexy admitted in our department between 2000 and 2017. RESULTS: We included 44 patients with PA. Their mean age was 50 ± 12.6 years. Among them, 31.8% had a known pituitary adenoma, and it was in all cases a macroadenoma, predominantly a prolactin secreting tumor (42.8%). A triggering factor of PA was encountered in 31.8% of cases and it was mainly: head trauma, dopamine antagonists, and hypertension. The clinical presentation of PA encompassed headaches (84.1%), visual disturbances (75%), and neurological signs (40.9%). Gonadotropin deficiency was the most frequent form of hypopituitarism noted (59.1%), followed by corticotropin deficiency (52.3%), thyrotropin deficiency (47.7%), and somatotropin deficiency (2.3%). Hormonal assessment at PA onset, concluded that 23 had a secreting adenoma: 18 prolactinomas, 3 ACTH-secreting adenomas, and 2 GH-secreting adenomas. In the 21 remaining cases, the tumor was non-functioning (47.7%). Pituitary MRI was performed in 42 cases (95.5%), revealing infraction and or hemorrhage in the pituitary gland in 33 cases; a heterogenous signal or a fluid level within the adenoma, in nine cases. Urgent administration of intra venous hydrocortisone was required in 19 cases. Mannitol administration was mandatory in a patient who had severe intracranial hypertension. Surgical management of the PA was imperative in 24 patients (54.5%): 15 suffered from severe visual impairment, 4 had an intracranial hypertension, 2 cases demonstrated an impaired consciousness, 2 patients experienced a tumor enlargement and one case had a severe Cushing's disease. Operative complications found were rhinorrhea attributable to cerebral spinal fluid leakage, insipidus diabetes associated with rhinorrhea, isolated insipidus diabetes, and hydrocephalus in one case each. Long-term follow-up concluded that headaches persisted in five cases, owing to the tenacity of a macroprolactinoma regardless of cabergoline treatment in one case, the recurrence of an adenoma in two cases and its persistence despite the medical and the surgical treatment in two patients. Concerning the visual acuity defects, only two patients had persistent diminished visual acuity at long-term follow-up. Among 25 patients, 13 were diagnosed with definitive thyrotropin deficiency. Similarly, 14 patients had persistent corticotropin deficiency (CD). Additionally, CD was de novo diagnosed in two patients. Otherwise, gonadotropin deficiency prevailed in all cases. Persistent prolactin deficiency was seen in two patients. Disappearance of the pituitary tumor was encountered in 11 out of 24 cases at long-term follow-up. Overall, surgery was associated with better outcome than conservative management. Pituitary apoplexy is a challenging condition due to its variable course, its diagnosis difficulty and management, as gaps remain to determine the best approach to treat this condition. CONCLUSIONS: To conclude, pituitary apoplexy is a challenging condition due to its variable course, its diagnosis difficulty and management, as gaps remain to determine the best approach to treat this condition. Further studies are thus needed.

Characteristics of adult-onset auto-immune type 1 diabetes.

BACKGROUND: Classically described as a disease of childhood and adolescence, diabetes mellitus type 1 (T1DM) can occur in adulthood. Adult-onset T1DM is poorly documented and is often misdiagnosed. This study aims to describe the epidemiological aspect of T1DM with adult-onset and detail its clinical, paraclinical, and therapeutic characteristics. MATERIALS AND METHODS: A 9-year retrospective longitudinal study (2011-2019) was conducted including adult patients (age >20 years) with confirmed diabetes and at least one of the auto-antibodies (auto-Abs) to glutamic-acid-decarboxylase (GAD), to islet-tyrosine-phosphatase 2 (IA2) or islet-cell-antibodies (ICA) positive. RESULTS: A total of 166 patients were included (sex-ratio M/F: 1.34; mean age: 28.6 years [20-56 years]). At the onset, 50.6% of patients presented with diabetic ketosis and 13.3% with diabetic ketoacidosis. Cardinal symptoms of diabetes were present in 30.7% of patients only at diagnosis, while the discovery was fortuitous in 5.4% of cases. 27.7% of patients developed an additional auto-immune disease mainly autoimmune thyroid disease. The risk of developing another AUTO-IMMUNE DISEASE was highest in females (p = 0.010) and increased with age (p = 0.011). GAD-Abs, IA2-Abs, and ICA were positive in 98.2%, 13.3%, and 17.4% of cases respectively. Only GAD-Abs were found positive in 73.1%. Upon diagnosis, 75.9% of patients were treated with insulin, while 24.1% of patients were initially put on oral anti-diabetic drugs before requiring insulin within an average of 7.42 months. CONCLUSIONS: Adult-onset T1DM has a different clinical course (slower onset, less abrupt symptoms, more insidious presentation, and more prolonged progression to insulin) that has to be known. Misdiagnosis of adult-onset T1DM can have serious consequences.

Insulinoma with equivocal imaging.

Summary: A 55-year-old patient was admitted to our department for the management of a repetitive alteration of consciousness. Biological investigation results were consistent with endogenous hyperinsulinemic hypoglycemia. Insulinoma was therefore suspected. Abdominal computed tomography and endoscopic ultrasound showed no obvious pancreatic mass.Somatostatin receptor scintigraphy showed abnormal radioactive uptake in both the pancreatic tail and the uncinate process. Contrariwise, abdominal magnetic resonance imaging showed a unique lesion in the pancreas tail. The patient was then proposed for pancreatic surgery. Both intraoperative manual palpation and intraoperative ultrasonography of the pancreas showed a single corporal lesion of 1.5 cm. No lesion was found in the uncinate process. After a left pancreatectomy, the lesion was histopathologically confirmed to be a well-differentiated neuroendocrine tumor. The symptoms of the patient resolved almost immediately following the surgery. The follow-up is one and a half years to date. Learning points: The exact preoperative localization of the pancreatic mass remains the most challenging part of insulinoma diagnostic workup. The radiologist's experience is the best warrantor to a precise localization of the tumor. 111In-DTPA-octreotide uptake in the pancreatic uncinate process may be physiological and its interpretation must, therefore, be vigilant. Manual palpation along with intraoperative ultrasonography is considered as the most effective method for the localization of insulinomas during open surgery.

Case report: Management challenges of late diagnosed 17-alpha hydroxylase deficiency.

Herein we report the intriguing case of a 42-year-old woman presenting with grade three hypertension, severe hypokalemia and primary amenorrhea, which revealed to be the complete form of 17 alphahydroxylase deficiency. We also discuss the challenging therapeutic approach as well as the outcomes and the follow-up of this patient.

Pheochromocytoma of the prostate: An unusual location.

Ectopic pheochromocytomas, also called paragangliomas, are defined as catecholamine -secreting tumors, which develop outside the adrenal medulla. Pheochromocytomas of the urinary tract represent less than 1% of all paragangliomas and are most commonly located in the bladder. Nevertheless, prostatic pheochromocytoma is an extremely rare clinical entity and only a few cases have been reported in the medical literature. Herein, we report a case of ectopic pheochromocytoma arising from the prostate, revealing with hypertensive crisis occurring immediately after ejaculation.

Analysis of ProP1 Gene in a Cohort of Tunisian Patients with Congenital Combined Pituitary Hormone Deficiency.

Background: Non-syndromic combined pituitary hormone deficiency (CPHD) occurs due to defects in transcription factors that govern early pituitary development and the specification of hormone-producing cells. The most common mutations are in the Prophet of Pit-1 (ProP1) gene. This work aims to (1) report findings of genetic analyses of Tunisian patients with non-syndromic CPHD and (2) describe their phenotype patterns and their evolution through life. Methods: Fifteen patients from twelve unrelated families with variable clinical phenotypes were included after excluding autoimmune and acquired forms of non-syndromic CPHD. Detailed pedigree charts and auxological, hormonal, radiological, and therapeutic details were recorded. Sanger sequencing was performed, and sequences were analyzed with a specific focus on coding and splice site regions of the ProP1 gene. Retained variants were classified using several in silico pathogenicity prediction tools and the VarSome platform. Results: We identified the common p.Arg73Cys mutation in seven patients from four unrelated pedigrees. We found a novel homozygous mutation (c.340C>T) in one sporadic case. This mutation generates a truncated ProP1 protein, predicted to be non-functional, lacking the last 112 codons (p.(Gln114Ter)). We confirmed by polymerase chain reaction (PCR) the absence of large exon deletions or insertions in the remaining sporadic patients (7/8). Conclusions: We report two mutations {one newly identified [p.(Gln114Ter)] and one previously reported (p.Arg73Cys)} in five unrelated Tunisian families with non-syndromic CPHD. This work is of clinical importance as it reports the high frequency of the p.Arg73Cys mutation in Tunisian CPHD families. Our study also illuminated the involvement of novel gene(s) in the emergence of non-syndromic CPHD.

The mitochondrial ND1 m.3337G>A mutation associated to multiple mitochondrial DNA deletions in a patient with Wolfram syndrome and cardiomyopathy.

Wolfram syndrome (WFS) is a rare hereditary disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is a heterogeneous disease and full characterization of all clinical and biological features of this disorder is difficult. The wide spectrum of clinical expression, affecting several organs and tissues, and the similarity in phenotype between patients with Wolfram syndrome and those with certain types of respiratory chain diseases suggests mitochondrial DNA (mtDNA) involvement in Wolfram syndrome patients. We report a Tunisian patient with clinical features of moderate Wolfram syndrome including diabetes, dilated cardiomyopathy and neurological complications. The results showed the presence of the mitochondrial ND1 m.3337G>A mutation in almost homoplasmic form in 3 tested tissues of the proband (blood leukocytes, buccal mucosa and skeletal muscle). In addition, the long-range PCR amplifications revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient's skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of moderate Wolfram syndrome associated with cardiomyopathy, in whom we detected the ND1 m.3337G>A mutation with mitochondrial multiple deletions.

A whole mitochondrial genome screening in a MELAS patient: a novel mitochondrial tRNA(Val) mutation.

Mitochondrial encephalopathy, lactic acidosis and strokelike episodes (MELAS) syndrome is a mitochondrial disorder characterized by a wide variety of clinical presentations and a multisystemic organ involvement. In this study, we report a Tunisian girl with clinical features of MELAS syndrome who was negative for the common m.3243A>G mutation, but also for the reported mitochondrial DNA (mtDNA) mutations and deletions. Screening of the entire mtDNA genome showed several known mitochondrial variants besides to a novel transition m.1640A>G affecting a wobble adenine in the anticodon stem region of the tRNA(Val). This nucleotide was conserved and it was absent in 150 controls suggesting its pathogenicity. In addition, no mutations were found in the nuclear polymerase gamma-1 gene (POLG1). These results suggest further investigation nuclear genes encoding proteins responsible for stability and structural components of the mtDNA or to the oxidative phosphorylation machinery to explain the phenotypic variability in the studied family.

Suprasellar Melanocytoma with Leptomeningeal Seeding: An Aggressive Clinical Course for a Histologically Benign Tumor.

INTRODUCTION: Meningeal melanocytoma (MM) is a very rare neuroectodermal neoplasm arising from the leptomeninges. Primary suprasellar melanocytomas are exceedingly rare, with only a handful of cases reported. The systemic spread of a nontransformed meningeal melanocytoma is an unusual occurrence. Herein, we report the first case of a primary sellar melanocytoma with cerebral and spinal meningeal seeding. Case Report. A 30-year-old male with no previous medical history presented to the endocrinology department with a loss of body hair. The endocrine workup concluded with isolated hypogonadotropic hypogonadism. The Magnetic Resonance Imaging (MRI) of the brain and sella revealed a large suprasellar mass continuous with the infundibulum of the pituitary gland. It was heterogeneously hyperintense on T1-, T2-, and FLAIR-weighted images and was enhanced with contrast, along with cerebral and spinal leptomeningeal spread. The patient was referred to the neurosurgery department, and a lumbar spine biopsy was indicated. The histopathological examination was suggestive of a grade I meningeal pigmented melanocytoma. CONCLUSION: Thus, primary sellar melanocytomas with leptomeningeal spread are an extremely rare phenomenon. Metastatic malignant melanoma should be ruled out. Being aware of differential diagnosis and the unusual behavior of meningeal melanocytoma will be necessary to manage the patient appropriately. Complete tumor resection is the best treatment whenever possible, and radiotherapy should be considered in case of unresectability or partial resection.