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Objective: Loss of libido, low serum testosterone levels, and other symptoms of hypogonadism like subfertility, gynecomastia, and immature testes, is a prevalent medical condition amongst males with advanced chronic liver disease. The purpose of this investigation was to evaluate the low serum testosterone levels association with hypogonadism in people with chronic liver disease. Study Duration: This study was carried out at Outpatient Department (OPD) of Medicine Ayub Teaching Hospital, Abbottabad from 1st January 2022 to 30th June 2022. Material and Methods: The retrospective study was completed on two hundred confirmed patients of hypogonadism with liver cirrhosis. In the repository, the available data was divided into two groups. The first group of chronic liver disease patients was diagnosed due to non-alcoholic fatty liver disease (NAFLD) and second patient group due to alcoholic liver disease (ALD). The patient in NAFLD group were in the age group between 15-30 years whereas the patients from ALD group were 30-60 years of age. The diagnostic values of total testosterone and Sex hormone binding globulin (SHBG) were collected from patient’s record. The independent t test was used for statistical analysis by using SPSS version 22. The frequency distribution of testosterone was also calculated between two types of chronic liver disease patients. Results: The retrospective research was performed. The data were dispersed across two age groups. The youth had no alcohol-related data, while the elderly had. According to hospital data, distribution was based on age between 15 and 30 years (NAFLD) and between 30 and 60 years (ALD). When T-test was applied it showed that there was no statistically significant difference found in means of SHBG between two age groups amongst chronic liver disease patients. In the case of serum testosterone, there was a statistically significant (p 0.05) difference between age groups (Table 1). Figures 1 and 2 illustrate the frequency distribution of total testosterone and its comparison within the liver cirrhosis group, respectively. Practical Implication: Our study predicted that low testosterone can raise the risk of mortality, the necessity for liver transplantation, and the likelihood of severe infection in men with cirrhosis given the mechanisms of action of testosterone. Conclusion: On the basis of two groups of liver cirrhosis, there is a significant age-related change in total serum testosterone, its control by the pituitary and it’s binding to SHBG in males over the age of forty. However, no substantial data was discovered in sex hormone binding globulin. Low testosterone levels are associated with hypogonadism in patients with cirrhosis of the liver. The effect of testosterone replacement treatment on increasing muscle quality in male cirrhotic patients remains to be determined. Safety and effectiveness of the treatment requires additional prospective research. Keywords: Sex Hormone Binding Globulin, Serum Testosterone, Hypogonadism, Chronic Liver Disease

Progressive pseudorheumatoid dysplasia or spondyloepiphyseal dysplasia tarda is caused by a mutation in Wnt1 inducible signalling pathway protein 3 (WISP3) and passes in an autosomal recessive manner. Prevalence underestimated as one per million and most of the cases remain undiagnosed or treated as Juvenile Idiopathic Arthritis (JIA). Differentiation between JIA and PPRD is really challenging however, this case is genetically confirmed from our country. 7-year-old, short stature boy, with multiple joint swellings of hands and feet, initially suspected to have JIA and had been worked up and took treatment for that for the past 2 years. He had progressive stiffness of small joints. Baseline biochemistry, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor and ANA, were within normal limits. He was moderately growth hormone deficient. Thyroid function tests and insulin-like growth factor 1 (IGF-1) were within reference ranges. Skeletal survey showed typical findings of pseudorheumatoid skeletal dysplasia. Physical therapy and genetic counselling were done.

Objectives To review the data of infants and children with suspected monogenic diabetes who underwent genetic testing. Methods Monogenic diabetes is a rare form of diabetes resulting from mutations in a single gene. It can be caused by dominant as well as recessive modes of inheritance. In a country like Pakistan where interfamily marriages are common the incidence of genetic disorders is increased. As Pakistan a resource-poor country, the diagnosis of insulin-dependent diabetes is often delayed and a genetic diagnosis of monogenic diabetes is extremely difficult. Children with clinical diagnosis of monogenic and syndromic diabates were recruited and blood samples were sent for genetic analysis. Results One thousand sixty four new cases diagnosed with type 1 diabetes were registered at the National Institute of Child Health, Karachi, in the last 10 years. Of these 39 patients were selected for genetic testing who were diagnosed with diabetes/had a sibling diagnosed with diabetes before the age of nine months (n = 27) or had extra pancreatic features ( n= 12). We identified mutations in 18/27 cases diagnosed with diabetes before nine months of age. The most common genetic subtype was WolcottRallison syndrome caused by EIF2AK3 mutations (seven cases). KCNJ11 mutations were identified in two cases, ABCC8mutations were identified in four cases from three families, GCK and INS mutations were each identified in two cases, and one SLC2A2 mutation was identified in one case. A genetic diagnosis was made in 12/12 children from six families with diabetes diagnosed after the age of nine months who had extrapancreatic features. Six patients had genetically confirmed Wolfram syndrome (WFS1), three had thiamine-responsive megaloblastic anemia (SLC19A2) and three were diagnosed with histocytosis lymphadenopathy plus syndrome (SLC29A3). Conclusions Genetic testing is essential to confirm a diagnosis of monogenic diabetes which guides clinical management and future counselling. Our study highlights the importance of diagnosing monogenic diabetes in the largely consanguineously-married population of Pakistan.

OBJECTIVE To determine the clinical presentation of Addison's disease in order to increase the awareness of presentation in Pakistani children. STUDY DESIGN Observational study. PLACE AND DURATION OF STUDY Department of Diabetes and Endocrinology, National Institute of Child Health, Karachi, Pakistan, from 2015 to 2019. METHODOLOGY Sixty-three children of Addison's disease were enrolled in the study, who have visited and facilitated from the services of National Institute of Child Health from urban and rural region of the Sindh province. Diagnosis were made through biochemical analysis and detailed examination of acute and chronic symptoms. Study was initiated after taking the approval from Institutional Review Board. Moreover, written informed consents were also taken from each of the study participant. RESULTS There were 36 boys and 27 girls with a mean age at diagnosis of 3.92 and 4.96 years, respectively. Twelve patients were presented with an adrenal crisis following an acute illness. All of them had hyponatraemia; however, 10 had a hyperkalaemia and 8 had been reported with hypoglycaemia. Increased skin pigmentation was observed in 45 children with other identifiable features including weight loss, lethargy, and poor response in activities. Moreover 15 of them were identified with associated disorder (autoimmune polyendocrinopattay syndrome (APS), Allgrove or triple A syndrome, and adrenoleukodystrophy). Conclusion: Typical and atypical presentations of Addison's disease in children of Pakistani population are defined in this study which may assist in better management of Addison's patients. Key Words: Adrenal crisis, Hyponatremia, Hyperkalemia, APS, Allgrove, Adrenoleukodystrophy.

Van Wyk Grumbach syndrome is well known for protracted hypothyroidism, characterised by multicystic ovaries (normal size ovaries contain many follicles of various sizes), isosexual precocious puberty and delayed skeletal growth. A series of ten children with Van Wyk Grumbach syndrome is been presented with their clinical features, biochemical and radiological profile and management. Patients showed a noteworthy improvement upon thyroxine therapy. It is vital to keep this entity in consideration and; hence, should investigate for thyroid status during the evaluation of ovarian cysts. Thyroxin replacement after establishing the diagnosis early can prevent the patient from going through extensive workup and surgeries. Key Words: Hypothyrodism, Multicystic ovaries, Isosexual precocious puberty.

Background & Objective: Spontaneous pregnancy loss has always been the frustrating experience for the couples and concern clinician. Chromosomal abnormality in either of the parent is considered to be the one of the leading cause of recurrent spontaneous miscarriages. This study was designed to evaluate the possible chromosomal etiology of miscarriage and the subsequent intimacy of maternal or paternal genetic abnormality. Methods: This case-control study was conducted between January 2016 and October 2016 at a tertiary care hospital in Karachi. A total of thirty-two couples were selected who had suffered with recurrent spontaneous miscarriages (RSM). Using conventional cytogenetic technique karyotyping was performed on all of the subjects. For the control twenty couples were also selected with no history of pregnancy loss. All the karyotypes were recorded on the standard method. Data was analyzed through SPSS version 22. Results: Among thirty-two cases nine cases were found to have abnormal karyotype. In which sex chromosomal trisomy=02 (46,XY/47,XXY), marker chromosome=01 (47,XX,+mar), Robertsonian translocation=01 (45,XY,der,(14:21),(q10;q10)), reciprocal translocation=01 (46,XX,t(11;22)(q23;q11.2)), inversion=02 (46,XX,inv(9)(p11q13)) and minor structural abnormalities=02 (46,XX,15PS+) were found. Approximately equal ratio with 1:1.25 was observed among male and female carrier respectively. Non-significant difference was found between the ages of both carriers (p=0.34). Though a significant different value was calculated in the case of number of miscarriage (p=0.004*). Moreover, no significant association was found among spontaneous miscarriage (SM) and recurrent spontaneous miscarriage (RSM) with respect to maternal age (p= 0.157). Conclusion: In the recent study possible chromosomal abnormalities suggested the evaluation of the patient with the history of recurrent spontaneous miscarriage must include conventional cytogenetic. Moreover, probe development and extended investigation can ease the prognosis among pregnancy related complication.

Background & Objective: Spontaneous pregnancy loss has always been the frustrating experience for the couples and concern clinician. Chromosomal abnormality in either of the parent is considered to be the one of the leading cause of recurrent spontaneous miscarriages. This study was designed to evaluate the possible chromosomal etiology of miscarriage and the subsequent intimacy of maternal or paternal genetic abnormality. Methods: This case-control study was conducted between January 2016 and October 2016 at a tertiary care hospital in Karachi. A total of thirty-two couples were selected who had suffered with recurrent spontaneous miscarriages (RSM). Using conventional cytogenetic technique karyotyping was performed on all of the subjects. For the control twenty couples were also selected with no history of pregnancy loss. All the karyotypes were recorded on the standard method. Data was analyzed through SPSS version 22. Results: Among thirty-two cases nine cases were found to have abnormal karyotype. In which sex chromosomal trisomy=02 (46,XY/47,XXY), marker chromosome=01 (47,XX,+mar), Robertsonian translocation=01 (45,XY,der,(14:21),(q10;q10)), reciprocal translocation=01 (46,XX,t(11;22)(q23;q11.2)), inversion=02 (46,XX,inv(9)(p11q13)) and minor structural abnormalities=02 (46,XX,15PS+) were found. Approximately equal ratio with 1:1.25 was observed among male and female carrier respectively. Non-significant difference was found between the ages of both carriers (p=0.34). Though a significant different value was calculated in the case of number of miscarriage (p=0.004*). Moreover, no significant association was found among spontaneous miscarriage (SM) and recurrent spontaneous miscarriage (RSM) with respect to maternal age (p= 0.157). Conclusion: In the recent study possible chromosomal abnormalities suggested the evaluation of the patient with the history of recurrent spontaneous miscarriage must include conventional cytogenetic. Moreover, probe development and extended investigation can ease the prognosis among pregnancy related complication. doi: https://doi.org/10.12669/pjms.35.5.678 How to cite this:Hanif MI, Khan A, Arif A, Shoeb E. Cytogenetic investigation of couples with recurrent spontaneous miscarriages. Pak J Med Sci. 2019;35(5):1422-1427. doi: https://doi.org/10.12669/pjms.35.5.678 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

OBJECTIVE To analyse chromosomal abnormalities of the patients who were referred for the screening of short stature and delayed puberty and to verify the association between karyotype and phenotype in confirmed Turner Syndrome (TS) patients. STUDY DESIGN Descriptive study. PLACE AND DURATION OF STUDY Department of Pediatric Endocrinology and Diabetes Unit-II, National Institute of Child Health, Karachi, from January 2011 to June 2016. METHODOLOGY Patients referred for the evaluation of short stature or delayed puberty were for the assessment of karyotype and phenotype correlations; standard karyotyping was executed and analysed on the basis of routine G-banding technique. Echocardiography and pelvic ultrasonography was also performed. RESULTS The study population consisted of 79 registered patients, with short stature and delayed puberty 48/79 (60.75%), short stature 68/79 (86.07%), and ambiguous genitalia 5/79 (6.32%). Conferring to the karyotype analysis, classical Turner Syndrome 45, X was found in 42/79 (53.16%), isochromosomes 13/79 (16.45%), and mosaicism was present in 11/79 (14.1%). Only 7/79 (8.86%) cases were diagnosed in infancy. CONCLUSION The results of the study showed the consistency of short stature and delayed puberty in most of patients. Monosomy of X chromosome was the commonest followed by isochromosomes, mosaicism and structural abnormalities of X chromosome. No remarkable difference was found among classical and non-classical TS patients' height.

Chromosomal numerical aberration is one of the leading reasons behind spontaneous pregnancy loss. The probability of spontaneous miscarriage increases with advance parental age. After miscarriage patients and their families feel desperate, which consequently create psychological illness. The review evaluates current techniques being used in the diagnosis and focuses toward a recently introduced molecular technique Quantitative Fluorescent-PCR (QF-PCR) which based on the use of fluorescent primers (probes). Several published articles were selected for the review regarding the frequency of spontaneous miscarriages, its reasons, and outcomes. Studies that focus on QF-PCR, karyotyping and their comparison were included. Current situation of management of spontaneous miscarriages was also observed through surveys and consultant views in Karachi. On the basis of the above mentioned piece of information, QF-PCR would be a good addition in the field of prenatal diagnosis. However, karyotyping is also a reliable method of prenatal diagnosis with little limitations.