Dihydropteridine reductase deficiency: The first Moroccan case report

Kaoutar Khabbache , Afaf Lamzouri , Hanaa Imlahi , Abdallah Oulmaati
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Abstract

Background

DHPRD (dihydropteridine reductase deficiency) is a very rare disorder that causes hyperphenylalaninemia (HPA), characterized by an accumulation of phenylalanine (Phe) and a profound deficit in the neurotransmitters dopamine and serotonin in the central nervous system with an alteration in folate status. It is an autosomal recessively inherited disorder caused by genetic changes in the QDPR gene.

Case presentation

A Moroccan 3-year-old girl, from a consanguineous marriage with a history of death and neurological illness in the siblings. The proband presents a very severe clinical picture; profound psychomotor delay with hypotonia, epileptic encephalopathy, abnormal movements and dysautonomia signs. The diagnosis of DHPRD was confirmed by DHPR activity assay and genetic testing. The patient was placed on a Phe-restricted diet and given augmented neurotransmitter therapy, which included levo-dopa/carbidopa, and 5-hydroxytryptophan with folinic acid. The improvement under treatment was not spectacular which is most likely due to the delay in diagnosis and management.

Discussion/conclusion

Significant advancements have been achieved in comprehending the physiopathology, the screening procedures, diagnostic techniques, treatment options, and molecular genetics pertaining to DHPRD. However, in countries where neonatal screening for phenylketonuria (PKU) is not established, severe forms of DHPRD with irreversible sequelae continue to be diagnosed. The long-term neurodevelopmental outcomes of patients with DHPRD are strongly influenced by early initiation of effective treatment; therefore, screening for PKU must be systematic and therapy should not be delayed.

二氢蝶啶还原酶缺乏症:摩洛哥首例病例报告
背景二氢蝶啶还原酶缺乏症(DHPRD)是一种非常罕见的疾病,可导致高苯丙氨酸血症(HPA),其特征是苯丙氨酸(Phe)蓄积,中枢神经系统的神经递质多巴胺和血清素严重缺乏,叶酸状态改变。这是一种常染色体隐性遗传疾病,由 QDPR 基因的遗传变化引起。病例介绍一名摩洛哥 3 岁女孩,来自近亲结婚,有兄弟姐妹死亡和神经系统疾病史。该患者的临床表现非常严重:严重的精神运动发育迟缓,伴有肌张力低下、癫痫性脑病、运动异常和自主神经功能障碍。通过 DHPR 活性测定和基因检测,确诊为 DHPRD。患者被安排限制 Phe 饮食,并接受神经递质强化治疗,包括左旋多巴/卡比多巴、5-羟色氨酸和亚叶酸。讨论/结论在了解 DHPRD 的生理病理、筛查程序、诊断技术、治疗方案和分子遗传学方面取得了重大进展。然而,在一些尚未开展新生儿苯丙酮尿症(PKU)筛查的国家,严重的 DHPRD 仍会被诊断出不可逆转的后遗症。及早开始有效治疗对 DHPRD 患者的长期神经发育结果有很大影响;因此,必须系统性地筛查 PKU,并且不应延误治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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