Molybdenum cofactor deficiency type B manifested as Leigh-like syndrome: a case report and literature review
10.3760/cma.j.cn112140-20200911-00866
- VernacularTitle:以Leigh样综合征为表现的钼辅因子缺乏症B型一例并文献复习
- Author:
Xiaojuan TIAN
1
;
Xin LI
;
Fang FANG
;
Zhimei LIU
;
Wenjuan WU
;
Kang LIU
;
Suzhen SUN
Author Information
1. 国家儿童医学中心 首都医科大学附属北京儿童医院神经内科 100045
- Keywords:
Leigh disease;
Hypouricemia;
MOCS2 gene;
Molybdenum cofactor deficiency
- From:
Chinese Journal of Pediatrics
2021;59(2):119-124
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the phenotypes and genotypes of molybdenum cofactor deficiency type B (MoCD-B) manifested as Leigh-like syndrome.Methods:The clinical data, laboratory tests, neuroimaging and gene results of one patient diagnosed as MoCD-B at Beijing Children′s Hospital and Hebei Children′s Hospital in December 2018 were collected. Related literature was searched and reviewed at Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed (up to September 2020) by using terms "MOCS2" "molybdenum cofactor deficiency" "Leigh-like syndrome,MOCS2" "molybdenum cofactor deficiency, Leigh-like syndrome". The phenotypes and genotypes of MoCD-B were summarized.Results:A 7 months and 14 days old boy with the chief complaint of "cough for 6 days, abnormal posture for 4 days and fever for 2 days" was admitted to Hebei Children′ Hospital on December 2018. His abnormal posture presented as opisthotonos accompanied with dysphagia, without seizures. His previous psychomotor development was described as normal. He was born at term after an uneventful pregnancy to non-consanguineous parents. Blood test showed a slightly increased lactic acid and a significantly decreased uric acid. Urine metabolism test showed an obviously increased xanthine and hypoxanthine. Brain magnetic resonance imaging showed hyperintense signal on T2 weighted image and fluid attenuated inversion recovery in bilateral globus pallidus and pedunculus cerebri. The patient was diagnosed with Leigh-like syndrome. No obvious improvement was achieved after cocktail therapy and symptomatic treatment. The whole exome sequencing showed that the patient carried a homozygous variant of MOCS2 gene, c.19G>T(p.Val7Phe), which was a previously reported pathogenic site in the literature and could cause MoCD-B. His parents carried a heterozygous variant respectively. A total of 41 MoCD-B cases with MOCS2 gene variants were collected through literature review and our study, among which 30 cases had full medical records. The onset ages of 23 (77%) cases were in neonate, manifesting with severe encephalopathy, including neonatal-onset intractable seizures, developmental delay, laboratory abnormalities included very low levels of serum and urinary uric acid, increased urinary levels of xanthine and hypoxanthine. Cranial imaging showed cerebral atrophy, cystic encephalomalacia, etc. The onset ages of 7 patients varied from 5 months to 23 years. Four cases had normal psychomotor development before disease onset. Neurological disorders appeared acutely or exacerbated after external triggers and all of them had basal ganglia involvement. Among the 30 cases, 3 cases had a relatively milder phenotype with the ability of brief communication and walking without or with support.Conclusions:Molybdenum cofactor deficiency is a rare disease. Most cases had severe phenotypes and poor outcomes, but some cases may have mild phenotype. MoCD-B caused by MOCS2 gene variants may manifest as Leigh-like syndrome with a normal psychomotor development before the trigger of infection strike. Hypouricemia, xanthinuria and hypoxanthinuria can be indicators of the disease. The presence of MOCS2 gene variants would confirm a final diagnosis.
