Genetics of Non-Syndromic Autosomal Recessive Mental Retardation

Non-syndromic mental retardation is one of the most serious neurodevelopmental disorders, which has a serious impact not only on the affected individuals and their families but also on the health care system and society. Previously research has been more focused on the X-linked mental retardation and only recently studies have shown that non-syndromic autosomal recessive mental retardation is extremely heterogeneous and contributes much more than the X-linked mental retardation. But very little is known about the genes and loci involved in nonsyndromic autosomal recessive mental retardation than the X-linked mental retardation. To date only thirty loci and ten genes have been established associated with the non-syndromic autosomal recessive mental retardation. This short review presents an overview of the current knowledge on clinical information available for the ten genes associated with this unexplored group of genetic disorde

Dyssegemental dyspalsia; Rolland-Desbuquois type--a case report from Pakistan

Two different forms of dyssegmental dysplasia can be distinguished; the lethal Silverman-Handmaker type and less severe Rolland-Desbuquois type. Patients with Rolland-Desbuquois type often survive beyond neonatal period. The purpose of this paper is to report a rare case of Dyssegmental dysplasia, Rolland-Desbuquois type from Pakistan

Ethical issues in managing lysosomal storage disorders in children in low and middle income countries

The lysosomal storage diseases are a group of rare, inherited metabolic diseases affecting about 1 in 7000 to 8000 people. In recent years, the introduction of enzyme replacement therapy, substrate reduction therapy and small molecule therapy, has changed the natural course of this otherwise progressive group of disorders leading to severe morbidity and early mortality. These treatment options, however, are extremely expensive and are needed for life thus presenting an economical as well as ethical challenge to the affected families and the health care system of a country. This paper presents a case for the prevention of the lysosomal storage disorders as a model for other inherited metabolic disorders in the form of antenatal testing and cascade screeningfor couples and families at risk of having affected off-springs and compares it to the cost incurred on the enzyme replacement therapy in the backdrop of the health care prioritiesof Pakistan, a low middle income country. Similar economic and ethical challenges are faced by most low and middle income countries. The literature search was done using Pubmed and Clinical trials databases using key words: Lysosomal storage disorders , natural course , ethics , cascade screening , Thalassemia and cascade screening . A total of 225 articles in English language were scanned from 1980-2016, 80 articles describing the natural course of LSD with and without ERT, ethical issues related to the treatment of LSD and strategies employed for the prevention of genetic disorders were prioritized

Diagnosis, treatment and follow-Up in four children with biotinidase deficiency from Pakistan

Biotinidase deficiency is an inherited disorder in which the vitamin biotin is not recycled. If untreated, affected individuals develop neurological and cutaneous symptoms. Untreated individuals with biotinidase deficiency either succumb to disease or are left with significant morbidity. We describe clinical course and follow-up of 4 children from Pakistan. All 4 presented with classical symptoms of biotinidase deficiency and responded dramatically to oral biotin within days to weeks. Biotinidase deficiency is reported in Pakistani children from different part of world, however; there is no such report from Pakistan. This highlights lack of awareness of biotinidase deficiency among physicians in Pakista

Glycogen storage diseases-time to flip the outdated diagnostic approach centered on liver biopsy with the molecular testing

The glycogen storage diseases (GSDs) are a group of inherited metabolic disorders that result from a defect in any one of several enzymes required for either glycogen synthesis or glycogen degradation. The traditional diagnostic approach is based on the invasive hepatic or muscle biopsies, which are neither cost effective nor convenient. Molecular (gene testing) has emerged over the course of past few years as a robust alternative diagnostic tool, which not only confirms the diagnosis of GSDs but also clearly differentiates the types of GSDs allowing the initiation of the type-specific appropriate treatment for the particular type of GSDs. The aim of this update is to highlight the limitations of undertaking a liver biopsy for the diagnosis of GSDs; and to further describe the pros of the molecular testing for better patient centered care

Newborn screening in Pakistan - lessons from a hospital-based congenital hypothyroidism screening programme.

We are living in a time of unprecedented increase in knowledge and rapidly changing technology. Such biotechnology especially when it involves human subjects raises complex ethical, legal, social and religious issues. The establishment of newborn screening programmes in developing countries poses major challenges as it competes with other health priorities like control of infectious diseases, malnutrition and immunization programmes. Despite this, it is imperative that the importance of newborn screening programmes is recognised by developing countries as it has been proven through decades of experience that it saves thousands of babies from mental retardation, death and other serious complications. Pakistan has an estimated population of 167 million inhabitants, 38.3% of whom are under 15 years of age. Pakistan lacks a national programme for newborn screening. However, as individual practice at the local level, Aga Khan University Hospital (AKUH) and a few other hospitals are doing newborn screening for congenital hypothyroidism. The main hurdle in the implementation of newborn screening in Pakistan is the lack of good infrastructure for health. Eighty percent of deliveries take place at home. Moreover, little resources are available for children identified with a genetic condition due to the non-existence of genetic and metabolic services in Pakistan. In a 20-year audit of congenital hypothyroid screening at AKUH we found 10 babies with congenital hypothyroidism. However due to missing data links spanning several years, we were unable to calculate its true incidence during this period. In order to estimate the incidence of congenital hypothyroidism (CH) we reviewed in detail data over 10 months in 2008, a period where there was better compliance for repeat thyroid stimulating hormone (TSH) testing, and found 2 babies with CH. This gave an estimated incidence of 1 in 1600 live births

Perspective on newborn screening (NBS): Evidence sharing on conditions to be included in NBS in Pakistan

Newborn screening aims at detecting treatable disorders early so that the treatment can be initiated to prevent mortality and morbidity. Such programmes are well established in most developed countries, and all newborns are screened for selected metabolic, endocrine and other disorders based on disease epidemiology, testing and treatment availability, efficiency and cost-effectiveness. Even in developing countries, such screening programmes are initiated using heel prick capillary blood collected on filter paper. The current narrative review was planned to provide a perspective with evidence in favour of starting newborn screening for different disorders. The programme project should be initiated nationwide, taking one disorder, congenital hypothyroidism, as the prototype and a newborn screening panel can then be extended to include other disorders. A task force should be set up to recommend disorders to be included in the panel, develop the national plan policies, and define procedures to strengthen the testing

Retrospective study of patients with hyperphenylalaninemia: Experience from a tertiary care center in Pakistan

Objective: To assess the clinical and biochemical features as well as outcome of perphenylalaninemia patients.Methods: The descriptive retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from January 2013 to February 2017 of plasma amino acid analysed at the Biochemical Genetic Laboratory of patients with phenylalanine levels \u3e120 umol/L. Medical charts of patients registered with the Metabolic Clinics were reviewed, while outside referrals were contacted by telephone to collect data on a pre-structured questionnaire. Data was analysed using SPSS 21. Results: Of the 18 patients, 13(72%) were males. Overall median age was 606 days (interquartile range: 761) and median phenylalanine levels were 1280 (interquartile range: 935) umol/L. Phenylalanine hydroxylase deficiency was present in 5(28%) patients while 3(16.6%) had defects in the metabolism or regeneration of tetrahydrobiopterin. The most common clinical features was intellectual deficit and seizures 14(78%) each, followed by lighter hair colour 10(55.5%) and hypotonia 11(61%). High treatment cost was the leading reason for cessation of therapy in 7(39%) followed by refusal by patient\u27s family 5(28%).Conclusion: Most hyperphenylalaninemia cases were diagnosed late when intellectual disability had already developed