Improved biochemical and neurodevelopmental profiles with high-dose hydroxocobalamin therapy in cobalamin C defect.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Inherited Metabolic Disease Pub Date : 2024-08-17 DOI:10.1002/jimd.12787
Giorgia Olivieri, Benedetta Greco, Sara Cairoli, Giulio Catesini, Francesca Romana Lepri, Lorenzo Orazi, Maria Mallardi, Diego Martinelli, Daniela Ricci, Raffaele Simeoli, Carlo Dionisi-Vici
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Abstract

Cobalamin C (Cbl-C) defect causes methylmalonic acidemia, homocystinuria, intellectual disability and visual impairment, despite treatment adherence. While international guidelines recommend parenteral hydroxocobalamin (OH-Cbl) as effective treatment, dose adjustments remain unclear. We assessed OH-Cbl therapy impact on biochemical, neurocognitive and visual outcomes in early-onset Cbl-C patients treated with different OH-Cbl doses over 3 years. Group A (n = 5), diagnosed via newborn screening (NBS), received high-dose OH-Cbl (median 0.55 mg/kg/day); Group B1 (n = 3), NBS-diagnosed, received low-dose OH-Cbl (median 0.09 mg/kg/day); Group B2 (n = 12), diagnosed on clinical bases, received low-dose OH-Cbl (median 0.06 mg/kg/day). Biochemical analyses revealed better values of homocysteine, methionine and methylmalonic acid in Group A compared to Group B1 (p < 0.01, p < 0.05 and p < 0.01, respectively) and B2 (p < 0.001, p < 0.01 and p < 0.001, respectively). Neurodevelopmental assessment showed better outcome in Group A compared to low-dose treated Groups B1 and B2, especially in Developmental Quotient, Hearing and Speech and Performance subscales without significant differences between Group B2 and Group B1. Maculopathy was detected in 100%, 66% and 83% of patients in the three groups, respectively. This study showed that "high-dose" OH-Cbl treatment in NBS-diagnosed children with severe early-onset Cbl-C defect led to a significant improvement in the metabolic profile and in neurocognitive outcome, compared to age-matched patients treated with a "low-dose" regimen. Effects on maculopathy seem unaffected by OH-Cbl dosage. Our findings, although observed in a limited number of patients, may contribute to improve the long-term outcome of Cbl-C patients.

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高剂量羟钴胺疗法改善了钴胺素 C 缺陷患者的生化和神经发育状况。
钴胺素 C(Cbl-C)缺陷会导致甲基丙二酸血症、同型胱氨酸尿症、智力障碍和视力损伤,尽管患者坚持治疗。虽然国际指南推荐肠外羟钴胺(OH-Cbl)是有效的治疗方法,但剂量调整仍不明确。我们评估了OH-Cbl疗法对早期Cbl-C患者生化、神经认知和视力结果的影响。A组(5人)通过新生儿筛查(NBS)确诊,接受高剂量OH-Cbl治疗(中位数为0.55毫克/千克/天);B1组(3人)通过NBS确诊,接受低剂量OH-Cbl治疗(中位数为0.09毫克/千克/天);B2组(12人)通过临床确诊,接受低剂量OH-Cbl治疗(中位数为0.06毫克/千克/天)。生化分析表明,与 B1 组相比,A 组的同型半胱氨酸、蛋氨酸和甲基丙二酸的数值更高(P<0.05)。
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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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