Identification of three novel pathogenic mutations in cystathionine beta-synthase gene of Pakistani intellectually disabled patients

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Muhammad Wasim ◽  
Haq N. Khan ◽  
Hina Ayesha ◽  
Mazhar Iqbal ◽  
Abdul Tawab ◽  
...  
Keyword(s):  
Black Hair ◽  
Hair Color ◽  
Full Potential ◽  
Missense Mutations ◽  
Intellectually Disabled ◽  
Inborn Errors ◽  
Northern Areas ◽  
Screening Study ◽  
Disabled Patients ◽  
Age Range

Abstract Background Classical homocystinuria (HCU) is an autosomal recessive inborn error of metabolism, which is caused by the cystathionine-β-synthase (CBS: encoded by CBS) deficiency. Symptoms of untreated classical HCU patients include intellectual disability (ID), ectopia lentis and long limbs, along with elevated plasma methionine, and homocysteine. Methods A total of 429 ID patients (age range: 1.6–23 years) were sampled from Northern areas of Punjab, Pakistan. Biochemical and genetic analyses were performed to find classical HCU disease in ID patients. Results Biochemically, nine patients from seven unrelated families were identified with high levels of plasma methionine and homocysteine. Targeted exonic analysis of CBS confirmed seven causative homozygous mutations; of which three were novel missense mutations (c.451G>T; p.Gly151Trp, c.975G>C; p.Lys325Asn and c.1039 + 1G>T splicing), and four were recurrent variants (c.451 + 1G>A; IVS4 + 1 splicing, c.770C>T; p.Thr257Met, c.808_810del GAG; p.Glu270del and c.752T>C; p.Leu251Pro). Treatment of patients was initiated without further delay with pyridoxine, folic acid, cobalamin, and betaine as well as dietary protein restriction. The immediate impact was noticed in behavioral improvement, decreased irritability, improved black hair color, and socialization. Overall, health outcomes in this disorder depend on the age and symptomatology at the time of treatment initiation. Conclusions With personalized treatment and care, such patients can reach their full potential of living as healthy a life as possible. This screening study is one of the pioneering initiatives in Pakistan which would help to minimize the burden of such treatable inborn errors of metabolism in the intellectually disabled patients.

Donors for Liver Transplantation

PEDIATRICS ◽  
1983 ◽  
Vol 71 (5) ◽  
pp. 856-857
Author(s):  
THOMAS E. STARZL ◽  
THOMAS R. HAKALA ◽  
J. THOMAS ROSENTHAL ◽  
DON DENNY
Keyword(s):  
United States ◽  
Liver Transplantation ◽  
Biliary Atresia ◽  
Inborn Errors Of Metabolism ◽  
The United States ◽  
Good Evidence ◽  
Full Potential ◽  
Inborn Errors ◽  
Infancy And Childhood ◽  
Liver Replacement

There is good evidence that the decade of the 1980s will witness an expansion of efforts to transplant extrarenal organs. This will have a profound effect in pediatrics, and particularly in the field of hepatology. The number of infants born with biliary atresia is not known with certainty, but it is likely that there are approximately 500 new cases each year in the United States. The number of lethal hepatic based inborn errors of metabolism that can be effectively treated with liver replacement has steadily grown. Other acquired hepatic disorders are not uncommon in infancy and childhood. If transplantation of the liver (or of the kidney, heart, intestine, pancreas, and possibly other organs) is to reach its full potential, pediatricians will have to be more acutely aware of the need for organs, and will need to collaborate actively in the procurement process.

scholarly journals The Role of gp91phox and the Effect of Tranexamic Acid Administration on Hair Color in Mice

2019 ◽  
Vol 20 (11) ◽  
pp. 2665 ◽  
Author(s):  
Keiichi Hiramoto ◽  
Yurika Yamate ◽  
Yutaka Takishita ◽  
Eisuke F. Sato
Keyword(s):  
Tranexamic Acid ◽  
Transforming Growth Factor ◽  
Hair Follicles ◽  
White Hair ◽  
Black Hair ◽  
Melanocortin Receptor ◽  
Control Group ◽  
Hair Color ◽  
Collagen Xvii ◽  
Acid Administration

We observed that on long-term breeding, gp91phox-knockout (gp91phox−/−) mice developed white hair. Here, we investigate the origin of this hitherto unexplained phenomenon. Moreover, we investigated the effect of tranexamic acid administration on the hair color in gp91phox−/− mice. We administered tranexamic acid (about 12 mg/kg/day) orally to 9-week-old C57BL/6j (control) and gp91phox−/− mice, thrice a week for 12 months. Compared to control mice, gp91phox−/− mice showed more white hair. However, the concentrations of reactive oxygen species and the levels of interleukin (IL)-1β and transforming growth factor (TGF)-β in the skin were lower than those in the control group. Furthermore, increase in white hair was observed in the control mice upon administration of the IL-1β antagonist. On the other hand, administration of tranexamic acid led to brown colored hair on gp91phox−/− mice. Although tranexamic acid treatment did not alter the expression levels of melanocortin receptor 1 and agouti signaling protein on hair follicles, it increased the expression of mahogunin ring finger protein 1 (MGRN1) and collagen XVII. These results suggested that retention of black hair requires the gp91phox/ROS/IL-1β/TGF-β pathway and that elevated levels of MGRN1 and collagen XVII lead to brown hair in gp91phox−/− mice.

scholarly journals Intellectual disability among Bhutanese refugees referred to psychiatric service of BPKIHS

2017 ◽  
Vol 13 (1) ◽  
pp. 23-29
Author(s):  
Binod Kumar Deo ◽  
L Mallick ◽  
D R Shakya ◽  
P M Shyangwa ◽  
N Sapkota ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Intellectual Disability ◽  
Neurological Disorders ◽  
Psychiatric Service ◽  
Mild Mental Retardation ◽  
Intellectually Disabled ◽  
Bhutanese Refugees ◽  
Seizure Disorders ◽  
Co Morbidity ◽  
Age Range

Background: Intellectual disability plays a significant role, especially in the field of rehabilitation. It becomes more important when people live in refugee camp for a long duration.Objective: To assess the level of intelligence and disability; and to sort out the illnesses comorbid with mental retardation in the Bhutanese refugees in eastern Nepal.Methods: Hospital based descriptive study was done using purposive sampling. Instruments used were: vineland social maturity scale, developmental screening test, seguin form board, standard progressive matrices and colored progressive matrices.Results: Samples were 42 with 64% females. Age range was 11-20 years. Among these referred cases, 45% had speech disorder and hearing loss and 31% had neurological disorders, including seizure disorders. Sixty-six percent had mild, 9% moderate and 19% severe mental retardation.Conclusion: Majority of the intellectually disabled Bhutanese refugees had mild mental retardation, followed by severe one. Seizure was a common co-morbidity in mental retardation. Health Renaissance 2015;13 (1): 

On patients who explode: surviving petrifying psychotherapeutic experiences

2021 ◽  
Vol 3 (2) ◽  
pp. 93-112
Author(s):  
Brett Kahr
Keyword(s):  
Criminal History ◽  
Depressive State ◽  
Clinical Experiences ◽  
Intellectually Disabled ◽  
Forensic Patients ◽  
Bodily Fluids ◽  
Careful Scrutiny ◽  
Disabled Patients ◽  
The Many

Although most of our patients will enter the consulting room quite quietly, often in a depressive state, having contained their sadistic impulses, a tiny fraction of those with whom we work will attack us in a variety of chilling ways. In this article, the author describes in detail two particularly terrifying clinical experiences in which a patient either threatened to kill him or actually sullied his consulting room with bodily fluids. Drawing upon his psychotherapeutic encounters not only with intellectually disabled patients and forensic patients but, also, with those who presented as ordinary “normal-neurotics”, the author considers the phenomenology of these “bomb”-like explosions and explains how he attempted to maintain a classical psychoanalytical focus of understanding, which consisted of a careful scrutiny of the countertransference and a firm commitment to the interpretation of unconscious material, whilst under attack. Furthermore, he examines the essential role of speaking with experienced colleagues who will provide essential supervision or assistance during these challenging chapters of clinical practice. The author also considers the many ways in which “bombs” can be hurled not only by the more obviously dangerous or disturbed individuals but, also, with surprising frequency, by those with no criminal history whatsoever, who, upon first encounter, often present as reasonably healthy.

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