Inherited disorders of gamma‐aminobutyric acid metabolism and advances in ALDH5A1 mutation identification

Inherited disorders of gamma‐aminobutyric acid (GABA) metabolism include succinic semialdehyde dehydrogenase (SSADH) and gamma‐aminobutyric acid transaminase (GABA‐T) deficiencies. The clinical features, pathophysiology, diagnosis, and management of both, and an updated list of mutations in the ALDH5A1 gene, which cause SSADH deficiency, are discussed. A database of 112 individuals (71 children and adolescents, and 41 adults) indicates that developmental delay and hypotonia are the most common symptoms arising from SSADH deficiency. Furthermore, epilepsy is present in two‐thirds of SSADH‐deficient individuals by adulthood. Research with murine genetic models and human participants, using [¹¹C] flumazenil positron emission tomography (FMZ‐PET) and transcranial magnetic stimulation, have led to therapeutic trials, and the identification of additional disruptions to GABA metabolism. Suggestions for new therapies have arisen from findings of GABAergic effects on autophagy, with enhanced activation of the mammalian target of rapamycin (mTOR) pathway. Details of known pathogenic mutations in the ALDH5A1 gene, three of which have not previously been reported, are summarized here. Investigations into disorders of GABA metabolism provide fundamental insights into the mechanisms underlying epilepsy, and support the importance of developing biomarkers and clinical trials. Comprehensive definition of phenotypes arising as a result of deficiencies in both SSADH and GABA‐T may increase our understanding of the neurophysiological consequences of a hyper‐GABAergic state.     

Prevalence of Mental Health Problems in Children and Its Associated Socio-Familial Factors in Urban Population of Semnan,Iran (2012)

Background:

The World Health Organization (WHO) defines mental health as “a state of well-being in which every individual realizes own potential, can cope with the normal pressures of life, is able to work effectively, and can make a contribution to community”.

Objectives:

Mental Health Problems (MHP) is a great concern for all societies in terms of its burden and impact. This survey screened MHP and its impact in an Iranian urban population aged 6 - 12 years old, and explored its associated socio-familial factors.

Patients and Methods:

The survey was conducted in the elementary schools of Semnan, using random cluster sampling. Collection and analysis of data was performed using the parent version of the “Strengths and Difficulties Questionnaire (SDQ)” and survey commands of Stata-nine, taking into account cluster effect and population weights. Associations were assessed by fitting simple and multiple logistic regression models. P < 0.05 was considered significant.

Results:

With regard to the SDQ total score, 19.3% (95% CI: 8.6, 30.1) scored above the normal threshold (9.6% abnormal, 9.7% borderline). The frequency of problems ranged between 16.1% (peer problems) and 8.4% (emotional symptoms), and in all subscales boys were affected more than girls. The impact score was abnormal in 68.4% of all children, and was greater in girls than in boys. “A previously diagnosed mental health disorder” (OR = 11.11, 95% CI: 5.55, 25.00), “male gender” (OR = 1.43, 95% CI: 1.10, 1.87 and “less time spent with the child by father” (OR = 1.61, 95% CI: 1.20, 2.17) were significantly associated with an abnormal SDQ.

Conclusions:

The high rate of MHP in 6 - 12 year-old children and the lack of any significant correlation with their age, underpins the importance of early screening for MHP in schools, with particular focus on high risk groups.     

High infection frequency,low diversity of Leishmania major and first detection of Leishmania turanica in human in northern Iran

Smears of suspected patients infected with zoonotic cutaneous leishmaniasis (ZCL) were stained and examined under a light microscopic observation. DNA of parasites within human ulcers was extracted directly from their smears. Nested PCR was used to amplify a fragment containing the internal transcribed spacers of the ribosomal RNA genes (ITS-rDNA) of Lesihmania parasites in human from Turkemen Sahara located in the northeastern part of Iran. Based on RFLP method by digesting BsuRI restriction enzyme and more precisely sequencing of DNA ITS-rDNA was shown to be species-specific. The infection rates of Leishmania parasites were high with 154 (93.9%) infections out of 164 suspected patients using microscopic observations. Only from 128 suspected patients out of 164, ITS-rDNA fragments were amplified and 125 samples had enough DNA to digest BsuRI restriction enzyme and do DNA sequencing. The Nested PCR assays detected not only Leishmania major but also Leishmania turanica for the first time, another parasite of the great gerbil in human. The density of L. major was high but the diversity was low with only 2 haplotypes. The overall ratio of L. major (123 infections) to L. turanica (2 infections) was significantly higher (Chi-squared test: p < 0.05). Infections of L. turanica are not reported only and/or not known to cause human disease. Our analytical framework conveys a clear understanding of both L. major and L. turanica which can only be approved as causative agents of ZCL by more extensive sampling and followed by standardized molecular diagnosis.     

Cancer of the pancreas in two brothers and one sister

Summary Over the past decades, pancreatic cancer has emerged as one of the most important malignancies in humans. This disease assumes a position of growing importance in view of its rising incidence and poor prognosis. Some familial pancreatic cancer has been reported with suggestions of hereditary, nutritional, home and familial environmental risk factors, and the possible role of genes in the development of this cancer among the members of one family. In an on-going case-control study of diet and cancer of the pancreas in Montreal, so far we were able to identify several familial cases of cancer of the pancreas. The most interesting case is the occurrence of this disease in two brothers and one sister all in their seventh decade of life. There was no history of pancreatitis among the cases or their relatives. Data from this study suggest that a familial predisposition to pancreatic cancer may occur in later decades of life. The role of genetic and environmental factors such as home remedies, familial food habits, etc., in the etiology of this cancer among these blood relatives, all in the same generation of one family, are unknown.