Roach Alexis N, Barkley Hannah, Rodriquez Carissa, Burrow T Andrew, Anderson Karl E, Shukla Ankita
Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
Department of Pediatrics, Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
Eur J Hum Genet. 2025 Aug;33(8):1080-1083. doi: 10.1038/s41431-024-01758-w. Epub 2024 Dec 11.
δ-Aminolevulinic acid (ALA) dehydratase (ALAD) deficient porphyria (ADP) is an extremely rare form of porphyria, with only eight documented cases. Herein, we report the second known case of ADP in the Western hemisphere and third case with infantile onset of symptoms. A male neonate presented on day three of life with profound hypotonia, pinpoint pupils, absent deep tendon reflexes, and anemia. Whole genome sequencing revealed two pathogenic missense ALAD variants, and subsequent biochemical testing confirmed a diagnosis of ADP. With supportive care and following erythrocyte transfusions for anemia, his hypotonia improved gradually. Neurological improvement following erythrocyte transfusion may have resulted from suppression of erythropoiesis and less overproduction of ALA and porphyrins by the marrow, which is an important consideration for long term management. This case highlights the importance of leveraging rapid whole genome sequencing for the diagnosis and minimization of devastating sequelae of exceptionally rare disorders, such as ADP.
δ-氨基乙酰丙酸（ALA）脱水酶（ALAD）缺乏性卟啉病（ADP）是一种极为罕见的卟啉病，仅有8例文献记载。在此，我们报告西半球第二例已知的ADP病例以及第三例有婴儿期症状发作的病例。一名男婴在出生后第三天出现严重肌张力减退、针尖样瞳孔、腱反射消失和贫血。全基因组测序发现两个致病性错义ALAD变异体，随后的生化检测确诊为ADP。通过支持治疗以及针对贫血进行红细胞输血后，他的肌张力减退逐渐改善。红细胞输血后神经功能改善可能是由于红细胞生成受到抑制以及骨髓中ALA和卟啉的过度生成减少，这是长期管理的一个重要考虑因素。该病例突出了利用快速全基因组测序来诊断和尽量减少诸如ADP等极为罕见疾病的毁灭性后遗症的重要性。
