Abstract：
BACKGROUND: Inborn errors of metabolism (IEM) are genetic diseases involving congenital disorders of enzyme activities. Most follow Mendelian autosomal recessive inheritance and few follow mitochondrial inheritance. In many cases, after the birth of an affected child parents discover that have been the carriers for the condition and worry about the risk of recurrence in future offspring. Preimplantation genetic testing (PGT) can analyze embryos before their transfer to the uterus and prevent the transmission of hereditary conditions to descendants, however this procedure is of limited value in mtDNA conditions.
METHODS: The list of diseases currently approved for PGT were reviewed. The process for eligibility, was as for the Comissão Nacional Procriação Medicamente Assistida (CNPMA), of Portugal (PT). Review of international practices for Assisted Reproductive Techniques (ART) in IEM was carried out.
RESULTS: As of 07.2022, 23 IEM diseases associated with deleterious variants in nDNA were approved for PGT in PT. Couples at risk for conditions not included in the list can solicit an evaluation from an expert committee, after a medical genetics consultation. To qualify for approval, diseases must cause significant suffering and/or premature death. Due to a greater number of solicitations many more IEM conditions have been approved for PGT across the world. ART for mtDNA is not available in PT. International expert centers include PGT for specific well documented variants and mitochondrial donation.
CONCLUSIONS: PGT is a reliable approach to reduce the risk of transmission of a genetic condition to the offspring. The list of IEM disorders currently accepted for this technique in Portugal are small, but it is expanding, as many more diseases fit the necessary criteria. While appealing in theory, low success rates coupled with limited availability can be discouraging for patients. Genetic counselling is of paramount importance after the diagnosis of IEM diseases. It is important for both clinicians and patients to be made aware of the available reproductive options and their limitations.
METHODS: The list of diseases currently approved for PGT were reviewed. The process for eligibility, was as for the Comissão Nacional Procriação Medicamente Assistida (CNPMA), of Portugal (PT). Review of international practices for Assisted Reproductive Techniques (ART) in IEM was carried out.
RESULTS: As of 07.2022, 23 IEM diseases associated with deleterious variants in nDNA were approved for PGT in PT. Couples at risk for conditions not included in the list can solicit an evaluation from an expert committee, after a medical genetics consultation. To qualify for approval, diseases must cause significant suffering and/or premature death. Due to a greater number of solicitations many more IEM conditions have been approved for PGT across the world. ART for mtDNA is not available in PT. International expert centers include PGT for specific well documented variants and mitochondrial donation.
CONCLUSIONS: PGT is a reliable approach to reduce the risk of transmission of a genetic condition to the offspring. The list of IEM disorders currently accepted for this technique in Portugal are small, but it is expanding, as many more diseases fit the necessary criteria. While appealing in theory, low success rates coupled with limited availability can be discouraging for patients. Genetic counselling is of paramount importance after the diagnosis of IEM diseases. It is important for both clinicians and patients to be made aware of the available reproductive options and their limitations.
摘要：
背景：先天性代谢错误（IEM）是涉及先天性酶活性紊乱的遗传疾病。大多数遵循孟德尔常染色体隐性遗传，很少遵循线粒体遗传。在许多情况下,在受影响的孩子出生后，父母发现这是该疾病的携带者，并担心未来后代复发的风险。植入前基因检测（PGT）可以在胚胎转移到子宫之前对其进行分析，并防止遗传性疾病传播给后代，然而，该程序在mtDNA条件下的价值有限。
方法：综述了目前批准用于PGT的疾病清单。资格的过程，至于国家医疗协会(CNPMA)，葡萄牙（PT）。对IEM中辅助生殖技术（ART）的国际惯例进行了审查。
结果：截至07.2022，23种与nDNA中有害变异相关的IEM疾病被批准用于PT中的PGT。面临未列入名单的条件的风险夫妇可以征求专家委员会的评估，在医学遗传学咨询之后.为了获得批准，疾病必须引起重大痛苦和/或过早死亡。由于更多的请求，世界各地的PGT已批准了更多的IEM条件。PT中没有mtDNA的ART。国际专家中心包括PGT，用于特定的有据可查的变体和线粒体捐赠。
结论：PGT是一种可靠的方法，可以降低遗传状况传播给后代的风险。目前在葡萄牙接受这种技术的IEM障碍列表很小，但它正在扩大，因为更多的疾病符合必要的标准。虽然理论上很有吸引力，低成功率加上有限的可用性可能会让患者感到沮丧。在诊断IEM疾病后，遗传咨询至关重要。对于临床医生和患者来说，重要的是要意识到可用的生殖选择及其局限性。
方法：综述了目前批准用于PGT的疾病清单。资格的过程，至于国家医疗协会(CNPMA)，葡萄牙（PT）。对IEM中辅助生殖技术（ART）的国际惯例进行了审查。
结果：截至07.2022，23种与nDNA中有害变异相关的IEM疾病被批准用于PT中的PGT。面临未列入名单的条件的风险夫妇可以征求专家委员会的评估，在医学遗传学咨询之后.为了获得批准，疾病必须引起重大痛苦和/或过早死亡。由于更多的请求，世界各地的PGT已批准了更多的IEM条件。PT中没有mtDNA的ART。国际专家中心包括PGT，用于特定的有据可查的变体和线粒体捐赠。
结论：PGT是一种可靠的方法，可以降低遗传状况传播给后代的风险。目前在葡萄牙接受这种技术的IEM障碍列表很小，但它正在扩大，因为更多的疾病符合必要的标准。虽然理论上很有吸引力，低成功率加上有限的可用性可能会让患者感到沮丧。在诊断IEM疾病后，遗传咨询至关重要。对于临床医生和患者来说，重要的是要意识到可用的生殖选择及其局限性。
