Abstract：
OBJECTIVE: Galactose mutarotase (GALM) deficiency was first reported in 2019 as the fourth type of galactosemia. This study aimed to investigate the clinical and genotypic spectra of GALM deficiency.
METHODS: This was a questionnaire-based retrospective survey conducted in Japan between February 2022 and March 2023.
RESULTS: We identified 40 patients with GALM deficiency in Japan (estimated prevalence: 1:181,835). Four of 38 patients (10.5%) developed cataracts, which resolved with lactose restriction in 3 out of 4 patients. Transient transaminitis was the most common symptom (23.1%). All of the patients followed lactose restriction; discontinuation of the restriction after infancy did not cause any complications. Moreover, none of the participants experienced long-term complications. Two variants, GALM NM_138801.3: c.294del and c.424G>A, accounted for 72.5% of the identified pathogenic variants. The patients showed moderately elevated blood galactose levels with lactose intake; however, the elevation was lower than that observed in galactokinase deficiency.
CONCLUSIONS: GALM deficiency is characterized by a similar but milder phenotype and lower blood galactose elevation than in galactokinase deficiency. Diagnosis and initiation of lactose restriction in early infancy should be essential for prevention of cataracts, especially in cases of irreversible opacity.
METHODS: This was a questionnaire-based retrospective survey conducted in Japan between February 2022 and March 2023.
RESULTS: We identified 40 patients with GALM deficiency in Japan (estimated prevalence: 1:181,835). Four of 38 patients (10.5%) developed cataracts, which resolved with lactose restriction in 3 out of 4 patients. Transient transaminitis was the most common symptom (23.1%). All of the patients followed lactose restriction; discontinuation of the restriction after infancy did not cause any complications. Moreover, none of the participants experienced long-term complications. Two variants, GALM NM_138801.3: c.294del and c.424G>A, accounted for 72.5% of the identified pathogenic variants. The patients showed moderately elevated blood galactose levels with lactose intake; however, the elevation was lower than that observed in galactokinase deficiency.
CONCLUSIONS: GALM deficiency is characterized by a similar but milder phenotype and lower blood galactose elevation than in galactokinase deficiency. Diagnosis and initiation of lactose restriction in early infancy should be essential for prevention of cataracts, especially in cases of irreversible opacity.
摘要：
目的：半乳糖变旋酶（GALM）缺乏症于2019年首次报道为第四类半乳糖血症。本研究旨在探讨GALM缺乏症的临床和基因型谱。
方法：这是一项基于问卷调查的回顾性调查，于2022年2月至2023年3月在日本进行。
结果：我们在日本确定了40例GALM缺乏症患者（估计患病率：1：181,835）。38例患者中有4例(10.5%)出现白内障,在四分之三的患者中，通过限制乳糖来解决。短暂性转胺炎是最常见的症状（23.1％）。所有患者均接受乳糖限制；婴儿期后停止限制不会引起任何并发症。此外，参与者均未出现长期并发症.两种变体，GALMNM_138801.3：c.294del和c.424G>A，占已鉴定致病变异的72.5%。患者表现出适度升高的血液半乳糖水平与乳糖摄入;然而，升高低于半乳糖激酶缺乏症。
结论：GALM缺乏症的特征是与半乳糖激酶缺乏症相似但更温和的表型和更低的血液半乳糖升高。在婴儿早期诊断和开始乳糖限制对于预防白内障至关重要。尤其是在不可逆的不透明的情况下。
方法：这是一项基于问卷调查的回顾性调查，于2022年2月至2023年3月在日本进行。
结果：我们在日本确定了40例GALM缺乏症患者（估计患病率：1：181,835）。38例患者中有4例(10.5%)出现白内障,在四分之三的患者中，通过限制乳糖来解决。短暂性转胺炎是最常见的症状（23.1％）。所有患者均接受乳糖限制；婴儿期后停止限制不会引起任何并发症。此外，参与者均未出现长期并发症.两种变体，GALMNM_138801.3：c.294del和c.424G>A，占已鉴定致病变异的72.5%。患者表现出适度升高的血液半乳糖水平与乳糖摄入;然而，升高低于半乳糖激酶缺乏症。
结论：GALM缺乏症的特征是与半乳糖激酶缺乏症相似但更温和的表型和更低的血液半乳糖升高。在婴儿早期诊断和开始乳糖限制对于预防白内障至关重要。尤其是在不可逆的不透明的情况下。
