Incidence of inborn errors of metabolism in British Columbia, 1969-1996
Incidence of inborn errors of metabolism in British Columbia, 1969-1996
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DOI：
10.1542/peds.105.1.e10
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发表时间：
2000-01-01
期刊：
影响因子：
8
通讯作者：
Lowry, RB
中科院分区：
文献类型：
--
作者：
Applegarth, DA;Toone, JR;Lowry, RB
Objective.确定加拿大不列颠哥伦比亚省每年有多少患有特定类型先天性代谢缺陷的儿童出生。这一人群为收集准确和统一的发病率数据提供了一个相对独特的环境，因为所有诊断都是通过一个实验室在一个普遍获得政府资助的医疗保健的人群中进行的。我们使用温哥华儿童医院生化疾病实验室（不列颠哥伦比亚省所有代谢诊断的中心转诊点）的记录来识别诊断为以下定义的代谢疾病的所有患者。我们获得的发病率数据仅包括1969年至1996年期间被确诊患有本文所述疾病并被证实在该省出生的儿童。所涵盖的疾病包括氨基酸、有机酸、尿素循环、半乳糖血症、原发性乳酸中毒、糖原累积病、溶酶体累积病以及特别涉及过氧化物酶体和线粒体呼吸链功能障碍的疾病。由于诊断特定疾病组所需的技术是在不同的时间到位的，我们对不同疾病组的数据对应于不同的时间框架。我们还调整了所用的时间框架，以考虑到某些疾病在出生后一段时间内可能不会得到医疗照顾的可能性。例如，在整个这一时间范围内对氨基酸疾病的发病率进行了评估，但过氧化物酶体疾病的发病率仅限于1984年至1996年，因为这是诊断所需技术到位和可靠的时间范围。大多数疾病组统计数据包括至少40万例出生。在不列颠哥伦比亚省出生的儿童中调查的代谢性疾病的总体最低发病率与每10万活产婴儿40例相似。这包括苯丙酮尿症（PKU）和半乳糖血症，这是由新生儿筛查计划检测。出生时未筛查的代谢性疾病，即从总数中减去PKU和半乳糖血症的代谢性疾病，其发病率最低，约为每10万例活产30例。这个诊断困境组将提交给儿科医生进行诊断。并非所有的代谢性疾病都进行了调查，我们的数据仅限于以下代谢性疾病组。每10万名新生儿中约有24名儿童（相当于调查的总疾病组的60%）患有涉及氨基酸（包括PKU）、有机酸、原发性乳酸酸中毒、半乳糖血症或尿素循环疾病的疾病。这些孩子都有涉及小分子的代谢疾病。每10万名新生儿中约有2.3名儿童（约5%）患有某种形式的糖原累积病。大约每100 000名新生儿中有8名（20%）患有溶酶体贮积病;每100 000名新生儿中有3名（7%-8%）患有基于呼吸链的线粒体疾病，每100 000名新生儿中有3至4名（7%-8%）患有过氧化物酶体疾病。涉及亚细胞器的疾病约占诊断难题组的一半。每一种诊断的特定疾病的发病率，包括明显罕见的疾病，如非酮症高甘氨酸血症，将在文本中找到。本次调查报告的代谢性疾病占我国人群单基因疾病总数的10%以上。我们的数据提供了一个很好的估计代谢性疾病的发病率，为调查的疾病组，在一个主要的白人人口。代谢性疾病的发病率数据很难收集，因为很少有中心的诊断集中在统一获得现代医疗保健的人群中，在研究过程中，我们的人群就是这种情况。我们预计需要有关代谢性疾病发病率的准确信息，作为如何为代谢性疾病提供诊断和治疗服务的指南，这些数据应有助于评估类似人群的此类需求。
Objective. To determine how many children with specific types of inborn errors of metabolism are born each year in British Columbia, Canada. This population provides a relatively unique setting for collection of accurate and uniform incidence data because the diagnoses are all made through one laboratory in a population with universal access to government-funded medical care.Methodology. We used the records of the Biochemical Diseases Laboratory, Children's Hospital, Vancouver (the central referral point for all metabolic diagnoses in British Columbia) to identify all patients diagnosed with the metabolic diseases defined below. We obtained incidence figures by including only the children diagnosed with the diseases covered in this article who were confirmed as having been born within the province for the years 1969 to 1996. The diseases covered were diseases of amino acids, organic acids, the urea cycle, galactosemia, primary lactic acidoses, glycogen storage diseases, lysosomal storage diseases, and diseases involving specifically peroxisomal and mitochondrial respiratory chain dysfunction. Because the technology needed for diagnosis of specific disease groups was in place at different times our data for the different disease groups correspond to different time frames. We have also adjusted the time frames used to allow for the likelihood that some diseases may not come to medical attention for some time after birth. For instance the incidence of amino acid diseases was assessed throughout the whole of this time frame but the incidence of peroxisomal diseases was restricted to 1984 to 1996 because this was the time frame during which the technology needed for diagnosis was in place and reliable. Most disease group statistics included at least 400 000 births.Results. The overall minimum incidence of the metabolic diseases surveyed in children born in British Columbia is similar to 40 cases per 100 000 live births. This includes phenylketonuria (PKU) and galactosemia which are detected by a newborn screening program. Metabolic diseases, which were not screened for at birth, ie, those with PKU and galactosemia subtracted from the total, have a minimal incidence of similar to 30 cases per 100 000 live births. This diagnostic dilemma group would present to pediatricians for diagnosis. Not all metabolic diseases have been surveyed and our data are restricted to the following metabolic disease groups. Approximately 24 children per 100 000 births (similar to 60% of the total disease groups surveyed) have a disease involving amino acids (including PKU), organic acids, primary lactic acidosis, galactosemia, or a urea cycle disease. These children all have metabolic diseases involving small molecules. Approximately 2.3 children per 100 000 births (similar to 5%) have some form of glycogen storage disease. Approximately 8 per 100 000 births (20%) have a lysosomal storage disease; similar to 3 per 100 000 births (7%-8%) have a respiratory chain-based, mitochondrial disease and similar to 3 to 4 per 100 000 (7%-8%) of births have a peroxisomal disease. The diseases involving subcellular organelles represent approximately half of the diagnostic dilemma group. The incidence of each of the specific diseases diagnosed, including apparently rare diseases such as nonketotic hyperglycinemia, is to be found in the text. The metabolic diseases reported in this survey represent over 10% of the total number of single gene disorders in our population.Conclusions. Our data provide a good estimate of metabolic disease incidence, for the disease groups surveyed, in a predominantly Caucasian population. Incidence data for metabolic diseases are hard to collect because in very few centers are diagnoses centralized for a population with uniform access to modern health care and this has been the case for our population during the course of the study. We foresee a need for accurate information on the incidence of metabolic diseases as a guide to how to provide diagnostic and therapeutic services for metabolic diseases and the figures should help in assessing such needs in similar populations.