Lysosomal storage disorders (LSD) are rare entities of recessive inheritance. The presence of a “founder” mutation in isolated communities with a high degree of consanguinity (e.g., tribes in the Middle East North Africa, MENA, region) is expected to lead to unusually high disease prevalence. The primary aim of this study was to estimate the prevalence of LSD and report their mutation spectrum in UAE. Between 1995 and 2010, 119 patients were diagnosed with LSD (65 Emiratis and 54 non-Emiratis). Genotyping was performed in 59 (50 %) patients (39 Emirati from 17 families and 20 non-Emiratis from 17 families). The prevalence of LSD in Emiratis was 26.9/100,000 live births. Sphingolipidoses were relatively common (9.8/100,000), with GM1-gangliosidosis being the most prevalent (4.7/100,000). Of the Mucopolysaccharidoses VI, IVA and IIIB were the predominant subtypes (5.5/100,000). Compared to Western countries, the prevalence of fucosidosis, Batten disease, and α-mannosidosis was 40-, sevenfold, and fourfold higher in UAE, respectively. The prevalence of Pompe disease (2.7/100,000) was similar to The Netherlands, but only the infantile subtype was found in UAE. Sixteen distinct LSD mutations were identified in 39 Emirati patients. Eight (50 %) mutations were reported only in Emirati, of which three were novel [c.1694G>T in the NAGLU gene, c.1336 C>T in the GLB1 gene, and homozygous deletions in the CLN3 gene]. Twenty-seven (42 %) patients were clustered in five of the 70 Emirati tribes. These findings highlight the need for tribal-based premarital testing and genetic counseling.
Even though lysosomal storage disorders (LSDs) are considered to be orphan diseases, they pose a highly relevant cause for morbidity and mortality as their cumulative prevalence is estimated to be 1:4,000. This is especially important as treatment in form of enzyme replacement therapy, substrate reduction therapy or stem cell transplantation is amenable for some LSDs. It is plausible that an early start of treatment might improve the overall prognosis and, even more important, prevent irreversible damage of key organs. To get a more precise insight into the real frequency of some LSDs in the general population, we screened 40,024 samples from the Hungarian newborn screening (NBS) program in Szeged for Fabry disease (FD), Gaucher disease (GD), Pompe disease (PD), and Niemann-Pick A/B (NPB) disease using tandem mass spectrometry. Altogether, 663 samples (1.66%) were submitted for retesting. Genetic confirmation was carried out for 120 samples with abnormal screening results after retesting, which identified three cases of GD, three cases of FD, nine cases of PD, and two cases with NPB. In some cases, we detected up to now unknown mutations – one in NPB and seven in PD – which raise questions about the clinical consequences of a NBS in the sense of late-onset manifestations. Overall, we conclude that screening for LSDs by tandem MS/MS followed by a genetic workup in identified patients is a robust, easy, valid, and feasible technology in newborn screening programs. Furthermore, early diagnosis of LSDs gives a chance to early treatment, but needs more clinical long-term data especially regarding the consequence of private mutations.
The aim of this study was to look at the spectrum of paediatric lysosomal disorders in Oman. Lysosomal storage disorders (LSDs) are a heterogeneous group of inherited metabolic diseases. Few studies on the birth prevalence and prevalence of LSDs have been reported from the Arabian Peninsula.
We studied 86 children with LSDs diagnosed over a period of nine years, from June 1998 to May 2007. Detailed clinical data, including age of onset, sex, age and mode of first presentation, and presence of consanguinity were collected.
Our data showed the combined birth prevalence for all LSDs in Oman to be around 1 in 4,700 live births. Sphingolipidoses was the most common group of disorder encountered (47.7%), followed by neuronal ceroid lipofuscinoses (NCL) (23.2%) and mucopolysaccharidoses (MPS) (23.2%). The proportion of consanguineous marriages in our series was found to be 87.5%.
Our data represent the birth prevalence and clinical spectrum of such disorders in Oman, one of the highly consanguineous societies in the Middle East.
Lysosomal storage disorders; Oman; Prevalence; Arabs
Lysosomal storage diseases (LSDs) are inherited metabolic disorders caused by deficient activity of a single lysosomal enzyme or other defects resulting in deficient catabolism of large substrates in lysosomes. There are more than 40 forms of inherited LSDs known to occur in humans, with an aggregate incidence estimated at 1 in 7,000 live births. Clinical signs result from the inability of lysosomes to degrade large substrates; because most lysosomal enzymes are ubiquitously expressed, a deficiency in a single enzyme can affect multiple organ systems. Thus LSDs are associated with high morbidity and mortality and represent a significant burden on patients, their families, the health care system, and society. Because lysosomal enzymes are trafficked by a mannose 6-phosphate receptor mechanism, normal enzyme provided to deficient cells can be localized to the lysosome to reduce and prevent storage. However, many LSDs remain untreatable, and gene therapy holds the promise for effective therapy. Other therapies for some LSDs do exist, or are under evaluation, including heterologous bone marrow or cord blood transplantation (BMT), enzyme replacement therapy (ERT), and substrate reduction therapy (SRT), but these treatments are associated with significant concerns, including high morbidity and mortality (BMT), limited positive outcomes (BMT), incomplete response to therapy (BMT, ERT, and SRT), life-long therapy (ERT, SRT), and cost (BMT, ERT, SRT). Gene therapy represents a potential alternative, albeit with its own attendant concerns, including levels and persistence of expression and insertional mutagenesis resulting in neoplasia. Naturally occurring animal homologues of LSDs have been described in all common domestic animals (and in some that are less common) and these animal models play a critical role in evaluating the efficacy and safety of therapy.
cat model; dog model; fucosidosis; glycogen storage; lysosomal storage disease; mannosidosis; mucopolysaccharidosis
Previous studies on the prevalence of mucopolysaccharidoses (MPS) in different populations have shown considerable variations. There are, however, few data with regard to the prevalence of MPSs in Fenno–Ugric populations or in north-eastern Europe, except for a report about Scandinavian countries. A retrospective epidemiological study of MPSs in Estonia was undertaken, and live-birth prevalence of MPS patients born between 1985 and 2006 was estimated. The live-birth prevalence for all MPS subtypes was found to be 4.05 per 100,000 live births, which is consistent with most other European studies. MPS II had the highest calculated incidence, with 2.16 per 100,000 live births (4.2 per 100,000 male live births), forming 53% of all diagnosed MPS cases, and was twice as high as in other studied European populations. The second most common subtype was MPS IIIA, with a live-birth prevalence of 1.62 in 100,000 live births. With 0.27 out of 100,000 live births, MPS VI had the third-highest live-birth prevalence. No cases of MPS I were diagnosed in Estonia, making the prevalence of MPS I in Estonia much lower than in other European populations. MPSs are the third most frequent inborn error of metabolism in Estonia after phenylketonuria and galactosemia.
Lysosomal storage diseases (LSDs) are a class of metabolic disorders caused by mutations in proteins critical for lysosomal function. Such proteins include lysosomal enzymes, lysosomal integral membrane proteins, and proteins involved in the post-translational modification and trafficking of lysosomal proteins. There are many recognized forms of LSDs, and although individually rare, their combined prevalence is estimated to be 1 in 8000 births. Over two-thirds of LSDs involve central nervous system (CNS) dysfunction—progressive cognitive and motor decline—and these symptoms are often the most debilitating. Although the genetic basis for these disorders are clear and the biochemistry of the proteins well understood, the cellular mechanisms by which deficiencies in these proteins disrupts neuronal viability remain ambiguous. In this review, we provide an overview of the widespread cellular perturbations occurring in LSDs, how they may be linked, and interventions that may specifically or globally correct those defects.
A retrospective study of the incidence and prevalence of paediatric inflammatory bowel disease over an 11 year period was undertaken in South Glamorgan. Over this time the incidence of Crohn's disease more than doubled from 1.30 cases per 100,000 childhood population per year in the period 1983-1988, to 3.11 cases per 100,000 population per year in the period 1989-1993. In contrast, the incidence of ulcerative colitis remained the same throughout the study period at 0.71 per 100,000 per year. In 1993 the prevalence of Crohn's disease in the childhood population was 16.6 per 100,000 and of ulcerative colitis, 3.42 per 100,000.
Occupational hepatitis B remains a threat to healthcare workers (HCWs) worldwide, even with availability of an effective vaccine. Despite limited resources for public health, the Czech Republic instituted a mandatory vaccination program for HCWs in 1983. Annual incidence rates of acute hepatitis B were followed prospectively through 1995. Despite giving vaccine intradermally from 1983 to 1989 and intramuscularly as half dose from 1990 to 1995, rates of occupational hepatitis B decreased dramatically, from 177 cases per 100,000 workers in 1982 (before program initiated) to 17 cases per 100,000 in 1995. Among high-risk workers, the effect was even more dramatic (from 587 to 23 per 100,000). We conclude that strong public-health leadership led to control of occupational hepatitis B among HCWs in the Czech Republic, despite limited resources that precluded administering full-dose intramuscular vaccine for much of the program. Application of a similar program should be considered for other countries in regions that currently do not have a hepatitis B vaccination program.
A survey of multiple sclerosis (MS) in the Cambridge Health District has identified 374 cases in a population of 288,410, giving a prevalence of 130 per 100,000. A total of 322 cases (86%) had either clinically definite or probable multiple sclerosis on 1 July 1990 (112 per 100,000) and 52 cases (14%) had suspected multiple sclerosis (18 per 100,000.) The incidence during 1989-91 was 5.94 per 100,000 per year. The prevalence figure is higher than in recent surveys from other southern parts of the United Kingdom, but correction for the age and sex characteristics of the at risk population eliminates these differences. The overall prevalence of multiple sclerosis is probably between 108 and 120 per 100,000 in the southern United Kingdom.
The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe (Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, and the United Kingdom) using a standardized case definition. A total of 5,522 cases were identified across the 11 countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infection showed remarkable congruence between countries. The risk of infection was highest among the elderly, and rates were higher in males than in females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue were the most common foci of infection, with 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%; it was 44% among patients who developed streptococcal toxic shock syndrome. The findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe.
In a national prevalence study of multiple sclerosis (M.S.) in the Republic of South Africa based on census day 1960 there were 118 individuals with M.S. who were born in Northern Europe (United Kingdom and other parts of North and Central Europe) and who had emigrated to the Republic by 1960. Their prevalence rate was 49 per 100,000 immigrants in comparison with a prevalence of 11 per 100,000 among native-born English-speaking white South Africans.
To study the possible effect of age at immigration it was necessary to relate the M.S. immigrants to the appropriate denominator—the population at risk according to age at immigration. The population at risk by age at immigration has been estimated by two methods in an indirect fashion with the assistance of the Bureau of Census (1960) and by surveys of the population at risk 1968-9. Both studies suggest that the risk of developing M.S. was reduced to less than a third of the expected risk among those who immigrated under the age of 15 or 16.
This study is further evidence that M.S. is an acquired exogenous disease, the precise nature of which is still not certain but, according to present knowledge, has as its leading contender the class of slow, latent, or temperate viruses.
The term Klinefelter syndrome (KS) describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. XXY aneuploidy is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males. Other sex chromosomal aneuploidies have also been described, although they are much less frequent, with 48,XXYY and 48,XXXY being present in 1 per 17,000 to 1 per 50,000 male births. The incidence of 49,XXXXY is 1 per 85,000 to 100,000 male births. In addition, 46,XX males also exist and it is caused by translocation of Y material including sex determining region (SRY) to the X chromosome during paternal meiosis. Formal cytogenetic analysis is necessary to make a definite diagnosis, and more obvious differences in physical features tend to be associated with increasing numbers of sex chromosomes. If the diagnosis is not made prenatally, 47,XXY males may present with a variety of subtle clinical signs that are age-related. In infancy, males with 47,XXY may have chromosomal evaluations done for hypospadias, small phallus or cryptorchidism, developmental delay. The school-aged child may present with language delay, learning disabilities, or behavioral problems. The older child or adolescent may be discovered during an endocrine evaluation for delayed or incomplete pubertal development with eunuchoid body habitus, gynecomastia, and small testes. Adults are often evaluated for infertility or breast malignancy. Androgen replacement therapy should begin at puberty, around age 12 years, in increasing dosage sufficient to maintain age appropriate serum concentrations of testosterone, estradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH). The effects on physical and cognitive development increase with the number of extra Xs, and each extra X is associated with an intelligence quotient (IQ) decrease of approximately 15–16 points, with language most affected, particularly expressive language skills.
Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disease subdivided into three phenotypes of increasing severity: Scheie, Hurler-Scheie and Hurler. To gauge the effectiveness of treatments and to determine the load likely to fall on health-care systems, it is necessary to understand the prevalence and natural progression of the disease especially with regard to life-expectancy. In general such data on the natural history of lysosomal storage diseases is sparse.
Analysis of prevalence and patient survival in MPS I disease using a unique longitudinal data set initiated and maintained over a period of more than 20 years by the Society for Mucopolysaccharide Diseases (UK).
The birth prevalence of MPS I in England and Wales over the period 1981 to 2003 was 1.07/100,000 births and within ± 5% of estimates reported in several studies that examined reasonably large populations. The median survival for MPS I patients (including all phenotypes irrespective of various treatments) was found by Kaplan-Meier analysis to be 11.6 years. This result was driven by the relatively poor survival of patients with the Hurler phenotype who, irrespective of any treatments received, had a median survival of 8.7 years; when censoring for receipt of bone marrow transplant (BMT) was implemented median survival of Hurler patients was diminished to 6.8 years. The difference between these survival curves was statistically significant by log rank test and can be attributed to beneficial effects of BMT and or selection of patients with superior prognosis for intervention with BMT. Survival curves for Hurler patients who received and did not receive BMT were very different. Probability of survival at 2 year after BMT was ~68% and was similar to this after 5 years (66%) and ten years (64%); the mean age of Hurler patients at receipt of BMT was 1.33 years (range 0.1 to 3 years). Follow up was insufficient to determine median survival of the milder phenotypes however, unsurprisingly, this was clearly superior to that for Hurler patients.
The birth prevalence of MPS I in England and Wales is 1.07/100,000 and the median survival for MPS I patients is 11.6 years.
Lysosomal storage diseases (LSD) are inherited disorders caused by deficiency of lysosomal enzymes in which early diagnosis is essential to provide timely treatment. This study reports interval values for the activity of lysosomal enzymes that are deficient in Mucopolysaccharidosis type I, Fabry, Gaucher and Pompe disease, using dried blood spots on filter paper (DBS) samples in a Brazilian population.
Reference activity values were obtained from healthy volunteers samples for alpha-galactosidase A (4.57 ± 1.37 umol/L/h), beta-glucosidase (3.06 ± 0.99 umol/L/h), alpha-glucosidase (ratio: 13.19 ± 4.26; % inhibition: 70.66 ± 7.60), alpha-iduronidase (3.45 ± 1.21 umol/L/h) and beta-galactosidase (14.09 ± 4.36 umol/L/h).
Reference values of five lysosomal enzymes were determined for a Brazilian population sample. However, as our results differ from other laboratories, it highlights the importance of establishing specific reference values for each center.
Orphan drugs are often approved under exceptional circumstances, requiring submission of additional data on safety and effectiveness through registries. These registries are mainly focused on one drug only and data is frequently incomplete. Some registries also address phenotypic heterogeneity and natural history data and publications on these aspects have contributed to the knowledge and awareness of these rare diseases. However, for the assessment of long-term outcomes and for cost-effectiveness, the incompleteness and variable quality of the data raises concerns on the usefulness of these registries. The existing registries for orphan drug treatments for lysosomal storage disorders (LSD's) illustrate these limitations. LSD's are inherited disorders of lysosomal metabolism with a wide variety in clinical symptoms, ranging from severe life-threatening neurological disease to mild or even asymptomatic cases. Their prevalence is extremely low and thus data is scarce and scattered all over Europe. In the past few years, several enzyme replacement therapies and an oral substrate inhibitor have been developed which provide lifelong treatment of LSD's. For Fabry disease, two enzymes were authorized at the same time resulting in two different drug registries being required by the European Medicines Agency (EMA) to monitor effectiveness and safety. This has lead to patient data being divided between two separate registries which may have contributed to delays in the assessment of important outcomes. Three treatments (including a recently approved new enzyme) have now been authorized for Gaucher Disease and two other potential therapies are in the pipeline. Dividing up the data on Gaucher disease patients in to five separate registries benefits nobody. We argue that disease specific (rather than drug specific) registries, supervised by independent clinicians are urgently needed for the best long-term evaluation of treatments of these rare diseases.
Lysosomal storage diseases (LSDs) are a class of genetic disorders in which proteins responsible for digestion or absorption of endocytosed material do not function or do not localize properly. The resulting cellular “indigestion” causes buildup of intracellular storage inclusions that contain unprocessed lipids and proteins that form macromolecular complexes. The buildup of storage material is associated with degenerative processes that are observed in all LSDs, albeit the correlation between the amount of storage inclusions and the severity of the degenerative processes is not always evident. The latter suggests that a specific mechanism set in motion by aberrant lysosomal function drives the degenerative processes in LSDs. It is becoming increasingly clear that in addition to their function in degrading endocytosed material, lysosomes are essential housekeeping organelles responsible for maintaining healthy population of intracellular organelles, in particular mitochondria. The present review surveys the current knowledge on the lysosomal-mitochondrial axis and its possible role as a contributing factor to mitochondrial Ca2+ homeostasis and to cell death in LSDs.
The incidence of hospital-diagnosed human hydatid disease acquired in the UK was estimated from a survey based on Hospital Activity Analysis data for the period 1974-83. The average annual incidence in Wales was 0.4 per 100,000 population compared with 0.02 per 100,000 in England. Within Wales, Powys, and particularly Brecknock, had the highest incidence (7 per 100,000 per year). Compared with the period 1953-62, the average annual incidence for Wales fell by half (from 0.8 to 0.4 per 100,000 per year), but in Powys the incidence did not decline, and in Brecknock and Montgomery there was a marginal increase. In comparison with 1953-62, the age-specific incidence in Wales and Powys decreased in each age group with the notable exception of children less than 15 years of age. This finding emphasizes that transmission of Echinococcus granulosus to humans is still occurring at hyper-endemic levels in parts of England and Wales and that control efforts should be intensified.
We conducted an epidemiologic study to understand temporal and spatial patterns of hemorrhagic fever with renal syndrome (HFRS) in the Republic of Korea (ROK). We estimated the incidence among civilians in endemic areas through the active surveillance system during the major epidemic periods, from September to December, between 1996 and 1998. We also estimated the prevalence among Korean military personnel from 1995 to 1998. In addition, we assessed seroprevalence, subclinical infection rate, and vaccination rates in both civilians and military personnel. The incidence in civilians ranged from 2.1 to 6.6 per 100,000 person-months. The annual prevalence in the military personnel was 40-64 per 100,000 military populations, and remained generally constant throughout the study period with seasonal variation. This is the prospective epidemiologic data set on HFRS in the ROK since the inactivated Hantaan virus vaccine was licensed for use in the late 1990s. These results will be invaluable in establishing a national immunization program against HFRS.
Hemorrhagic Fever with Renal Syndrome; Hantaan virus; Epidemiology; Incidence; Prevalence; Korea
Lysosomal storage disorders (LSD) are a rare cause of non immunological hydrops fetalis (NIHF) and congenital ascites. The reported incidence is about 1%. The incidence of idiopathic NIHF is estimated to be about 18%.
Patients and methods
We report four cases with transient hydrops fetalis resulting from LSD and performed a literature review on LSD with NIHF and congenital ascites in combination.
At present, 12 different LSDs are described to be associated with NIHF or congenital ascites. Most patients had a family history of NIHF, where the preceding sibling had not been examined. A diagnostic approach to the fetus with NIHF due to suspected LSD either in utero or postnatal is suggested. Transient forms of NIHF and/or ascites in association with MPS IVA, MPS VII and NPC are described for the first time in this publication.
LSD should be considered in transient hydrops. Enzymatic studies in chorionic villous sample or amniotic cultured cells, once the most common conditions associated with fetal ascites or hydrops have been ruled out, are important. This paper emphasizes the fact that LSD is significantly higher than the estimated 1% in previous studies, which is important for genetic counseling as there is a high risk of recurrence and the availability of enzyme replacement therapy for an increasing number of LSD.
Non-immunological hydrops fetalis; Lysosomal storage disease; Transient hydrops; Congenital ascites; Clinical approach
Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia.
STUDY OBJECTIVE--To use routine statistical records to estimate the incidence and prevalence of treated schizophrenia. DESIGN AND SETTING--Analysis of linked records in Oxfordshire (population 540,000) for all people in contact with specialist psychiatric services from 1975-86. SUBJECTS--Records of 685 people with a diagnosis of schizophrenia as an inpatient and a further 294 people who received specialist psychiatric care for schizophrenia outside hospital without any record of inpatient care. MEASUREMENTS AND MAIN RESULTS--The measures most commonly recorded in psychiatric statistics, first admission rates for people in whom schizophrenia was recorded at their first psychiatric admission, were 8.7 per 100,000 males and 5.6 per 100,000 females. First contact rates for people in whom schizophrenia was recorded at any time in the study period and in any setting were 15.1 per 100,000 males and 11.4 per 100,000 females. Whichever patient population was analysed, the broad profile of schizophrenia by age, sex, and calendar time was similar. CONCLUSIONS--First admission rates for schizophrenia, as identifiable in current routine information systems, are useful indicators of the general pattern of disease but are inadequate absolute indicators of treated incidence. These data are limited to the first ever contact. Reliable information about the treated incidence of disease requires information systems which incorporate information about when and where each diagnosis was first made. Reliable information about treated prevalence requires systems which also incorporate data about death, recovery, and migration into and out of the study population.
The prevalence of known cases of acromegaly in Northern Ireland in 1984 was 6.3 per 100,000 population. The incidence of newly-diagnosed cases over the preceding 25 years was 5.5 patients per year, or 0.4 patients per 100,000 population per year. This rate would be equivalent to about 200 new cases per year in the United Kingdom. Four options have been available to most of these patients--surgical hypophysectomy (transfrontal or transsphenoidal), pituitary radiotherapy (usually external cobalt beam), drug treatment with bromocriptine, or no treatment. Choice of treatment has been mainly influenced by tumour size, with the larger pituitary adenomas having surgery initially. No single form of treatment has been successful in achieving a clinical remission or cure in more than a minority of cases. The most successful outcome has been where total pituitary ablation has been achieved. Life-table analysis for the whole group shows life expectancy which is not markedly different for that of an age-matched population from Northern Ireland. Morbidity related to long term osteoarthritis and treatment complications remain a major problem. The incidence of malignant tumours is higher than would be expected.
BACKGROUND AND OBJECTIVES:
Individual inborn errors of metabolism (IEM) are rare disorders, but may not be that uncommon in our patient population. We report the incidence of IEM in a defined cohort of births at the Saudi Aramco medical facilities in the Eastern Province of Saudi Arabia over 25 years.
The records of all patients diagnosed with IEM from 1 January 1983 to 31 December 2008 were reviewed and categorized according to accumulated or deficient metabolites into small-molecule disorders (aminoacidemia, organic acidopathies [OA], urea cycle defects, fatty acid oxidation, and carbohydrate metabolic disorders) and other disorders, including glycogen and lysosomal storage disorders (LSDs), and organelle disorders.
During the study period, 165 530 Saudi Arabian infants were born at Saudi Aramco and 248 were diagnosed with an IEM, corresponding to a cumulative incidence of 150 cases per 100 000 live births. Small-molecule disorders were diagnosed in 134/248 patients (54%). OA were the most common (48/248 patients; 19%), and methylmalonic aciduria was the most frequently observed OA (13/48 patients; 27%). LSDs were diagnosed in 74/248 patients (30%), and mucopolysaccharidosis was the most frequently observed LSD (28/74; 38%).
We believe that our data underestimate the true incidence of IEM in the region. Regional and national newborn screening programs will provide a better estimation of the incidence of IEM. We recommend a centralized newborn screening program that employs tandem mass spectrometry.
Rapid increases in the incidence of adenocarcinoma of the esophagus have been reported among white men. We further explore the temporal patterns among white individuals by sex, stage, and age by use of data from the Surveillance, Epidemiology, and End Results program for 22,759 esophageal cancer cases, of which 9,526 cases were adenocarcinoma, diagnosed from January 1, 1975, through December 31, 2004. Among white men, increases in the incidence of esophageal cancer were largely attributed to the 463% increase in the incidence of adenocarcinoma from 1.01 per 100,000 person-years in 1975−1979 to 5.69 per 100,000 person-years in 2000−2004 (95% confidence intervals [CI]=0.90 to 1.13 and 5.47 to 5.91, respectively). A similar rapid increase is now clearly apparent among white women, among whom the adenocarcinoma rate increased 335% from 0.17 to 0.74 per 100,000 person-years (95% CI= 0.13 to 0.21 and 0.67 to 0.81, respectively) over the same time period. Adenocarcinoma rates rose among white men and women regardless of stage and age groups, indicating that these increases are real and not an artifact of surveillance.
During the 25-year period 1970–1994 694 patients were diagnosed with neck sprain resulting from a car accident at the Emergency Room of the University Hospital Groningen. The purpose of the present study was to analyse the prevalence, groups at risk and trends in these patients, taking into account changes in the number of cars per inhabitant and the average number of kilometres driven. We defined the population as car accident victims diagnosed with neck sprain. Binominal tests were used to obtain measures of statistical significance. Over the 25-year period a steady increase in the number of these patients was observed, from 10 in 1970 to 122 in 1994. The highest prevalence was found for the age group 25- to 29-year olds (28.3 per 100,000), followed by 40- to 44-year-olds (27.9 per 100,000). Across the life span, the male: female ratio was 1 : 0.98. Eight percent of the victims were treated as inpatients. The increase in the number of car accident victims with neck sprain appears not to be an isolated phenomenon, because a parallel rise in the number of cars per inhabitant and in the average number of kilometres driven was found. No direct relation was observed between seat belt legislation and the increase in neck sprain injuries. The effect of the media on awareness of the consequences of car accidents is discussed.
Key words Neck sprain; Whiplash; life span; Prevalence