A Novel Homozygous Variant in the MCOLN1 Gene Associated With Severe Oromandibular Dystonia and Parkinsonism.

BACKGROUND: Mucolipidosis type IV (MLIV) is a rare, progressive lysosomal storage disorder characterized by severe intellectual disability, delayed motor milestones and ophthalmologic abnormalities. MLIV is an autosomal recessive disease caused by mutations in the MCOLN1 gene, encoding mucolipin-1 which is responsible for maintaining lysosomal function. OBJECTIVES AND METHODS: Here, we report a family of four Iranian siblings with cognitive decline, progressive visual and pyramidal disturbances, and abnormal movements manifested by severe oromandibular dystonia and parkinsonism. MRI scans of the brain demonstrated signal abnormalities in the white matter and thinning of the corpus callosum. RESULTS AND CONCLUSIONS: Whole-exome sequencing identified a novel homozygous variant, c.362C > T:p. Thr121Met in the MCOLN1 gene consistent with a diagnosis of MLIV. The presentation of MLIV may overlap with a variety of other neurological diseases, and genetic analysis is an important strategy to clarify the diagnosis. This is an important point that clinicians should be familiar with. The novel variant c.362C > T:p. Thr121Met herein described may be related to a comparatively older age at onset. Our study also expands the clinical spectrum of MLIV associated with the MCOLN1 variants and introduces a novel likely pathogenic variant for testing in MLIV cases that remain unresolved.

Estimation of Ambulation and Survival in Neurodegeneration with Brain Iron Accumulation Disorders.

BACKGROUND: Neurodegeneration with Brain Iron Accumulation (NBIA) disorder is a group of ultra-orphan hereditary diseases with very limited data on its course. OBJECTIVES: To estimate the probability of preserving ambulatory ability and survival in NBIA. METHODS: In this study, the electronic records of the demographic data and clinical assessments of NBIA patients from 2012 to 2023 were reviewed. The objectives of the study and factors impacting them were investigated by Kaplan-Meier and Cox regression methods. RESULTS: One hundred and twenty-two genetically-confirmed NBIA patients consisting of nine subtypes were enrolled. Twenty-four and twenty-five cases were deceased and wheelchair-bound, with a mean disease duration of 11 ± 6.65 and 9.32 ± 5 years. The probability of preserving ambulation and survival was 42.9% in 9 years and 28.2% in 15 years for classical Pantothenate Kinase-Associated Neurodegeneration (PKAN, n = 18), 89.4% in 7 years and 84.7% in 9 years for atypical PKAN (n = 39), 23% in 18 years and 67.8% in 14 years for Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN, n = 23), 75% in 20 years and 36.5% in 33 years for Kufor Rakeb Syndrome (KRS, n = 17), respectively. The frequencies of rigidity, spasticity, and female gender were significantly higher in deceased cases compared to surviving patients. Spasticity was the only factor associated with death (P value = 0.03). CONCLUSIONS: KRS had the best survival with the most extended ambulation period. The classical PKAN and MPAN cases had similar progression patterns to loss of ambulation ability, while MPAN patients had a slower progression to death. Spasticity was revealed to be the most determining factor for death.

Neurodegeneration with Brain Iron Accumulation Disorders and Retinal Neurovascular Structure.

BACKGROUND: The unique neurovascular structure of the retina has provided an opportunity to observe brain pathology in many neurological disorders. However, such studies on neurodegeneration with brain iron accumulation (NBIA) disorders are lacking. OBJECTIVES: To investigate NBIA's neurological and ophthalmological manifestations. METHODS: This cross-sectional study was conducted on genetically confirmed NBIA patients and an age-gender-matched control group. The thickness of retinal layers, central choroidal thickness (CCT), and capillary plexus densities were measured by spectral domain-optical coherence tomography (SD-OCT) and OCT angiography, respectively. The patients also underwent funduscopy, electroretinography (ERG), visual evoked potential (VEP), and neurological examination (Pantothenate-Kinase Associated Neurodegeneration-Disease Rating Scale [PKAN-DRS]). The generalized estimating equation model was used to consider inter-eye correlations. RESULTS: Seventy-four patients' and 80 controls' eyes were analyzed. Patients had significantly decreased visual acuity, reduced inner or outer sectors of almost all evaluated layers, increased CCT, and decreased vessel densities, with abnormal VEP and ERG in 32.4% and 45.9%, respectively. There were correlations between visual acuity and temporal peripapillary nerve fiber layer (positive) and between PKAN-DRS score and disease duration (negative), and scotopic b-wave amplitudes (positive). When considering only the PKAN eyes, ONL was among the significantly decreased retinal layers, with no differences in retinal vessel densities. Evidence of pachychoroid was only seen in patients with Kufor Rakeb syndrome. CONCLUSION: Observing pathologic structural and functional neurovascular changes in NBIA patients may provide an opportunity to elucidate the underlying mechanisms and differential retinal biomarkers in NBIA subtypes in further investigations. © 2023 International Parkinson and Movement Disorder Society.

Olfactory status in neurodegeneration with brain iron accumulation disorders.

BACKGROUND: Olfactory dysfunction has been suggested as a diagnostic and discriminative biomarker in some neurodegenerative disorders. However, there are few studies regarding the olfactory status in rare diseases including neurodegeneration with brain iron accumulation (NBIA) disorders. METHODS: Genetically-confirmed NBIA patients were enrolled. Neurological and cognitive examinations were conducted according to the Pantothenate Kinase-Associated Neurodegeneration-Disease Rating Scale (PKAN-DRS) and the Mini-Mental State Examination (MMSE) questionnaire, respectively. Olfaction was assessed in three domains of odor threshold (OT), odor discrimination (OD), odor identification (OI), and total sum (TDI) score by the Sniffin' Sticks test. The olfactory scores were compared to a control group and a normative data set. RESULTS: Thirty-seven patients, including 22 PKAN, 6 Kufor Rakeb syndrome, 4 Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN), 5 cases of other 4 subtypes, and 37 controls were enrolled. The mean PKAN-DRS score was 51.83±24.93. Sixteen patients (55.2%) had normal cognition based on MMSE. NBIA patients had significantly lower olfactory scores compared to the controls in TDI and all three subtests, and 60% of them were hyposmic according to the normative data. Including only the cognitively-normal patients, still, OI and TDI scores were significantly lower compared to the controls. The phospholipase A2-Associated Neurodegeneration (PLAN) and MPAN patients had a significantly lower OI score compared to the cognitively-matched PKAN patients. CONCLUSION: Olfactory impairment as a common finding in various subtypes of NBIA disorder can potentially be considered a discriminative biomarker. Better OI in PKAN compared to PLAN and MPAN patients may be related to the different underlying pathologies.

Transcranial sonography in neurodegeneration with brain iron accumulation disorders.

BACKGROUND: Transcranial Sonography is a non-invasive technique that has been used as a diagnostic tool for a variety of neurodegenerative disorders. However, the utility and potential application of this technique in NBIA disorders is scarce and inconclusive. METHODS: In this cross-sectional retrospective case-control study, the echogenicity of Substantia Nigra (SN), Lentiform Nucleus (LN), and Diameter of the Third Ventricle (DTV) were assessed by TCS in genetically confirmed NBIA patients referring to the movement disorder clinic. The normal echogenicity area of SN was defined based on the 90th percentile of an age-and-gender-matched control group. NBIA patients underwent neurologic examination at each visit, but their brain magnetic resonance imaging and demographics were extracted from electronic records. RESULTS: Thirty-five NBIA patients of four subtypes with a mean disease duration of 10.54 years and 35 controls were enrolled. The normally defined SN echogenicity in controls was 0.23 cm2. DTV and SN echogenicity areas were significantly higher in patients compared to the controls (P = 0.002 and < 0.001, respectively). Around 85% and 63% of the patients showed LN and SN hyperechogenicity at least on one side, respectively. Disease duration was positively correlated with DTV (r = 0.422, p = 0.015). Cases with Pantothenate Kinase Associated Neurodegeneration (n = 23) also had significantly higher DTV and SN echogenicity area compared to the controls. CONCLUSION: Despite most NBIA patients displayed increased DVT and higher SN and LN hyperechogenicity than healthy controls, the discriminatory role of TCS on different NBIA subtypes remains to be determined.

Urinary and circulatory netrin-1 as biomarker in diabetes and its related complications: a systematic review and meta-analysis.

BACKGROUND: Novel biomarkers have been suggested for the diagnosis and prognosis of diabetes mellitus. The biomarker utility of netrin-1 in diabetes as an extracellular protein has been investigated. In this systematic review and meta-analysis, we reviewed the role of netrin-1 as a biomarker in prediabetes, diabetes, and complications of diabetes. METHODS: PubMed, Embase, Scopus, and Web of Science were systematically searched for studies that measured circulatory and/or urinary netrin-1 levels in diabetes and compared them with non-diabetic patients or evaluated the prognostic role of this marker. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using random-effect meta-analysis to compare netrin-1 levels between groups. The impact of mean age, male sex percentage, sample size, mean body mass index, and publication year on the overall heterogeneity was assessed using meta-regression. RESULTS: Among 413 records from international databases, 19 original studies were included with 2061 cases (1137 diabetics, 196 prediabetics, and 728 healthy controls). Meta-analysis of eight studies measuring netrin-1 in patients with diabetes and comparing it with healthy controls showed no significant difference between the two groups (SMD 0.69, 95% CI -0.78 to 2.16, I2 = 98%, p-value = 0.36). On the other hand, a meta-analysis of netrin-1 levels in patients with prediabetes in comparison with healthy controls revealed that they had lower levels (SMD -0.51, 95% CI -0.81 to -0.21, p-value < 0.01). Diabetic patients with microalbuminuria and macroalbuminuria had significantly higher circulatory netrin-1 levels compared to normoalbuminuric group SMD 1.18, 95% CI 0.83 to 1.53, p-value < 0.01 and SMD 1.67, 95% CI 0.76 to 2.58, p-value < 0.01, respectively). Moreover, no difference in urinary netrin-1 levels was found between micro-, macro-, and normoalbuminuric groups (p-value > 0.05). CONCLUSION: Netrin-1 showed promising results as a biomarker in diabetes prognosis. However, more studies are required to confirm our findings, and higher sample size studies are needed to evaluate the diagnostic utility of this marker.

Huntington's disease and neurovascular structure of retina.

BACKGROUND: Retinal biomarkers in neurodegenerative disorders have attracted much attention in recent years. Recent studies have reported visual dysfunction in Huntington's disease (HD). However, little is known about retinal structural changes in HD. METHODS: A total of 50 subjects, including 25 motor-manifest HD patients and 25 gender- and age-matched controls, were enrolled. Unified Huntington's Disease Rating Score-Motor part was assessed in HD patients. Spectral-domain Optical Coherence Tomography (SD-OCT) was used to evaluate the macular thickness and peripapillary retinal nerve fiber layer (pRNFL). Superficial and deep capillary plexus densities were measured using OCT angiography (OCTA). To account for inter-eye correlation, generalized estimating equation (GEE) model was used. RESULTS: HD patients had a significant reduction in macular thickness in both inner and outer superior sectors and the inferior outer sector. Inferior pRNFLs were significantly decreased in thickness. There was no significant difference in retinal capillary plexus density between the two groups. Age and disease duration were negatively correlated with macular thickness in HD patients. However, the severity of motor involvement was not correlated with SD-OCT or OCTA parameters. CONCLUSIONS: We observed attenuated pRNFL and macular retinal thickness in patients with HD, independent of macular capillary plexus parameters. It can support the hypothesis that the retina may be a potential biomarker for monitoring the neurodegenerative process in HD.

Biodegradability, physical, mechanical and antimicrobial attributes of starch nanocomposites containing chitosan nanoparticles.

This study aimed to develop a plasticized starch (PS) based film loaded with chitosan nanoparticles (CNPs, 1, 2, 3, and 4%) as a reinforcing and antibacterial agent. We examined the morphology, biodegradability, mechanical, thermo-mechanical, and barrier properties of the PS/CNPs films. The antimicrobial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria was investigated by colony forming unit (CFU) and disc diffusion methods. A dense structure was obtained for all PS/CNPs films and, thus, their complete biodegradation occurred in more days than neat PS. The increase in the CNPs percentage led to improved mechanical behaviour and barrier properties. PS-CNPs composite films revealed inhibition zones against both E. coli and S. aureus, with the 100% reduction in CFU against S. aureus. The current study exhibited that PS-CNPs films were more effective in inhibiting bacteria growth than neat PS film, confirming the composite films potential application as antimicrobial food packaging.

A study of depression, partnership and sexual satisfaction in patients with post-traumatic olfactory disorders.

Post-traumatic olfactory dysfunction (PTOD) is associated with a significant decrease in quality of life. The present study aimed to explore whether PTOD is associated with depression and changes in sexuality. There were two groups in this case-control study. The patient group consisted of patients with PTOD (n = 55), and the control group comprised healthy individuals without the olfactory disorder (n = 115). Olfactory function, depression, partnership, and sexual satisfaction were assessed using the Iranian version of the Sniffin' Sticks test (Ir-SST), Beck Depression Inventory (BDI), Enrich Couple Scale (ECS) and Sexual Satisfaction Scale for Women (SSSW). The BDI scores were higher in the patient group than in the control group (p < 0.001). The SSSW score was lower in the patient group than in controls (p < 0.01), although the ECS score was not significantly different between patients and controls. Also, there was no significant difference in the severity of trauma between marital satisfaction and sexual satisfaction. However, the analysis showed a statistically significant difference in depression scores in connection with the head trauma severity. In the PTOD group, depression was increased and sexual satisfaction declined. Understanding the association of olfactory dysfunction with depression and sexuality allows patients and doctors to deal with less notable consequences of this disorder.

Frequency and outcome of olfactory impairment and sinonasal involvement in hospitalized patients with COVID-19.

BACKGROUND: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined. OBJECTIVE: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19. METHODS: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients. RESULTS: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91%) patients complained of olfactory loss and in 6 (6.52%) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39%) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26%). Fifteen patients (16.3%) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07). CONCLUSIONS: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss.

Impact of exosome-loaded chitosan hydrogel in wound repair and layered dermal reconstitution in mice animal model.

Combat or burn injuries are associated with a series of risks, such as microbial infection, an elevated level of inflammatory response, and pathologic scar tissue formation, which significantly postpone wound healing and also lead to impaired repair. Skin engineering for wound healing requires a biomimetic dressing substrate with ideal hydrophilicity, holding antioxidant and antimicrobial properties. In addition, available bioactive specification is required to reduce scar formation, stimulate angiogenesis, and improve wound repair. In this study, we successfully fabricated chitosan (Ch)-based hydrogel enriched with isolated exosome (EXO) from easy-accessible stem cells, which could promote fibroblast cell migration and proliferation in vitro. Full-thickness excisional wound model was used to investigate the in vivo dermal substitution ability of the fabricated hydrogel composed Ch and EXO substrates. Our finding confirmed that the wounds covered with Ch scaffold containing isolated EXO have nearly 83.6% wound closure ability with a high degree of re-epithelialization, whereas sterile gauze showed 51.5% of reduction in wound size. In summary, obtained results imply that Ch-glycerol-EXO hydrogel construct can be utilized at the full-thickness skin wound substitution and skin tissue engineering.

Validity and Reliability of Persian Smell Identification Test.

INTRODUCTION: Smell Identification Tests (SIT) are routinely utilized for the clinical evaluation of olfactory function. Since Iran consists of various ethnic subgroups, the reliability and validity of this test as a national SIT are required to be evaluated across the country. MATERIALS AND METHODS: This cross-sectional study evaluated the cultural adaptation of SIT administered to 420 healthy volunteers from 6 various ethnic subgroups (i.e., Fars, Turk, Kurd, Lor, Baluch, and Arab) living in 7 cities (one city for each subgroup, and Tehran [capital of Iran] with mixed ethnicities). The SIT consists of pens pre-filled with 24 odorants. The correct identification response rate was evaluated in all and each subgroup. The test was performed twice on 60 participants with a 2-week interval to assess its reliability. The SIT was further administered to 150 cases with documented abnormal olfactory function to evaluate its validity. RESULTS: The correct identification response rate was estimated at 70% for all odorants in all and each subgroup. The mean odor identification score was 21.41±1.37 (score range: 17- 24) with no significant difference among various subgroups. Moreover, the test-retest correlation coefficient was obtained at 0.77. The mean odor identification score in patients with olfactory impairment was 10.69±3.76, which was significantly different from that in healthy participants (P<0.001). The best cut-point for the beginning of olfactory impairment was 17.5 (95% CI: 9-100, Sensitivity=99, Specificity=81). Females obtained higher scores of odor identification, compared to males (P=0.025). CONCLUSION: The results indicated the reliability and validity of the SIT, which can be used nationally for the assessment of olfactory function in various ethnic subgroups across the country.

Evaluation of Phenotypic and Genotypic Characteristics of Carbapnemases-producing Enterobacteriaceae and Its Prevalence in a Referral Hospital in Tehran City.

BACKGROUND & OBJECTIVE: Carbapenem-resistant Enterobacteriaceae is a growing concern worldwide including Iran. The emergence of this pathogen is worrying as carbapenem is one of the 'last-line' antibiotics for treatment of infections caused by multi drug resistant gram- negative bacteria. The main objective of this study was to determine the prevalence of carbapenem-resistant Enterobacteriaceae in a referral hospital in Tehran, Iran. METHODS: In this study, all positive isolates of Enterobacteriaceae recorded in blood, urine, and other body fluids were studied during April 2017 to April 2018 in a referral hospital in Tehran. All cases of resistance to carbapenems were first tested by modified Hodge test. All cases with positive or negative test, after gene extraction, were examined genotypically based on the primers designed for the three Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-ß-lactamase (NDM), and OXA-48 genes by conventional PCR method. RESULTS: 108 isolates (13.6%) were resistant to all cephalosporins as well as to imipenem and meropenem. In a genotypic study, including 45 isolates, 13 isolates were positive for OXA-48 gene, 11 isolates for OXA-48 and NDM genes, 11 isolates for OXA-48, NDM and KPC genes, 4 isolates for OXA-48 genes and KPC, 3 isolates for NDM, one isolate for KPC. On the other hand, two isolates were negative for all three genes examined. CONCLUSION: OXA-48 gene was one of the most common genes resistant to carbapenems in Iran. According to studies, the prevalence of antibiotic resistance in Iran is rising dramatically, which reduces the choice of antibiotics to treat severe infections in the future.

"Infection prevention and control idea challenge" contest: a fresh view on medical education and problem solving.

BACKGROUND: Healthcare-associated infections (HAIs) challenge modern medicine. Considering their high prevalence in Iran, we aimed to provide knowledge on the subject, and to teach about the importance of infection prevention and control (IPC) to a broad audience of pre-graduate healthcare professionals, focusing on education as the cornerstone of IPC. MAIN BODY: We invited Iranian medical students to present ideas on "how to reduce HAIs." Projects were eligible if being original and addressing the call. Accepted projects were quality assessed using a scoring system. Forty-nine projects were submitted, of which 37 met the inclusion criteria. They had a mean score of 69.4 ± 18.3 out of the maximum possible score of 115. Four reviewers assessed the 37 projects for clinical applicability, impact on patient safety, and innovation, and selected the best 12 to compete at the 2nd International Congress on Prevention Strategies for Healthcare-associated Infections, Mashhad, Iran, 2018. The competition took place in three rounds. The selected teams presented their projects in the first round and debated one by one in a knockout manner, while the jury reviewed their scientific content and presentation skills. In the second round, the top 5 projects competed for reaching the final stage, in which the teams presented their ideas in front of a panel of international IPC experts to determine the first three ranks. At the end of the contest, the participants gained valuable criticisms on how to improve their ideas. Moreover, by its motivating atmosphere, the contest created an excellent opportunity to promote IPC in medical schools. CONCLUSIONS: Using innovation contests in pre-graduates is an innovative education strategy. It sensitizes medical students to the challenges of IPC and antimicrobial resistance and drives them to think about solutions. By presenting and defending their innovations, they deepen their understanding on the topic and generate knowledge transfer in both ways, from students to teachers and vice versa.

Investigating the prevalence of risk factors of papillary thyroid carcinoma recurrence and disease-free survival after thyroidectomy and central neck dissection in Iranian patients.

Background: Papillary thyroid carcinoma (PTC) is considered the most frequent thyroid malignancy (85-90%) with a good prognosis. However, its frequent recurrence increases mortality and morbidity. In this inquiry we investigated the prevalence of risk factors of PTC recurrence and disease free survival after thyroidectomy and central neck dissection. Method: In this retrospective study, all patients with confirmed PTC who underwent total thyroidectomy and central neck dissection in Imam Reza and Omid hospitals of Mashhad University of Medical Sciences from 2004 to 2011 were included. Total locoregional and distant recurrence rate, 5-year disease free survival rate (DFS) and contributing factors of recurrence were investigated after at least 5 years. Results: In this study 289 patients were included with a mean follow-up of 72.90 ± 11.02 months. 70.6% were female and 29.4% were male. Recurrence occurred in 58 cases from which 10 were distant and 48 were loco-regional. 5-year DFS was 80% and total-survival-rate was 99%. Our analysis showed that primary tumor size, vascular-invasion, extra-thyroid extension, and lymph node ratio (LNR) were significantly related to DFS.

Gamma Knife stereotactic radiosurgery for cerebellopontine angle meningioma.

OBJECTIVE: Meningiomas comprise 6-15 % of cerebellopontine angle (CPA) tumors. Surgical treatment is a real challenge because this area is occupied by several critical neurovascular elements. Currently, surgery is the first choice of treatment, however several factors may be present that necessitate choosing the alternative treatments such as Gamma Knife Stereotactic Radiosurgery (GKS). PATIENTS AND METHODS: Ninety-three patients with CPA meningioma who were treated by GKS for a period of 8 years, were retrospectively reviewed. Factors affecting clinical and radiological improvement were analyzed. RESULTS: The median tumor volume was 6 cm3. The mean values for maximal and marginal dose were 20.2 and 13.6 Gy, respectively. The mean follow-up time was 31.5 months. Tumor control (lack of progression) was achieved in 96.8% of the patients and 55.9% of the patients showed tumor regression on follow-up MRI. The actuarial 3-year progression-free survival (PFS) rate was 96%. Clinical improvement was seen in 49.5% of the patients while 11.8% experienced worsening or new-onset symptoms. Adverse radiation effects were seen in 4.3% of the patients. A worse symptomatic outcome, male sex, a lower tumor coverage, and marginal doses <13.5 Gy were associated with worse radiologic outcomes. Worse radiologic outcomes and higher tumor volumes, especially tumor volumes ≥8.5 cc, were associated with worse symptomatic outcomes. The male sex was associated with a lower PFS. CONCLUSION: Gamma Knife radiosurgery, either primarily or post- operatively, offers a decent long-term tumor control in CPA meningioma, and is associated with an acceptable complication profile, especially in tumors with lower volumes.

Iranian neonatal diabetes mellitus due to mutation in PDX1 gene: a case report.

BACKGROUND: Neonatal diabetes mellitus with hyperglycemia during the first 6 months of life is a rare disorder that can occur in all races and societies. CASE PRESENTATION: In this study, we introduced an Iranian (Persian) 65-day-old patient with neonatal diabetes mellitus with novel homozygous mutation in the pancreatic and duodenal homeobox 1, PDX1, gene, which is also known as IPF1 gene, located in exon 2. This case was a newborn boy born in Vali-Asr Hospital, Tehran; he was diagnosed as having hyperglycemia on 28th day. Genetic analysis detected a homozygous mutation on PDX1 gene on chromosome 13. It is a novel homozygous mutation in the PDX1 gene (NM_000209.3), p.Phe167Val. This mutation was confirmed by Sanger sequencing. There was no evidence of agenesis of the pancreas. CONCLUSIONS: We reported a case of neonatal diabetes mellitus due to novel homozygous mutation in the PDX1 gene without exocrine pancreas manifestations.

Risk Factors for Hearing Loss and Its Prevalence in Neonates Older than 6 Months with History of Hospitalization in Intensive Care Unit.

OBJECTIVES: Hearing loss is one of the most important disabilities in neonates. Delay in the detection of hearing loss leads to impaired development and may prevent the acquisition of speech. We aimed to determine the risk factors associated with hearing loss in neonatal patients aged more than 6 months with a history of hospitalization in Neonatal Intensive Care Unit (NICU). METHODS: In this case-control study, screening for hearing loss was carried out on 325 neonates aged 6-12 months referred to Pediatric Neurology Office of Vali-e-Asr Hospital, Tehran, Iran up to 2011. Hearing loss was confirmed using Auditory Brainstem Response screening test (ABR). RESULTS: The prevalence of mildly and moderately hearing loss in neonates was determined as 3.6%. The most significant risk factors for hearing loss in neonates were neonatal icterus associated with phototherapy, respiratory distress syndrome (RDS) and lower Apgar score. CONCLUSION: It seems to quantitative auditory system screening using ABR is necessary for all neonates; because rehabilitation support such as speech therapy and hearing training in this age period is more effective than older ages.