Clinical presentation, gene analysis and outcomes in young patients with early-treated combined methylmalonic acidemia and homocysteinemia (cblC type) in Shandong province, China

Han, Bing; Cao, Zhiyang; Tian, Liping; Zou, Hui; Yang, Lin; Zhu, Wenzhen; Liu, Yingxia

doi:10.1016/j.braindev.2015.10.016

Cited by 50 publications

(52 citation statements)

References 17 publications

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“…Comparisons of total plasma homocysteine, methionine, and methylmalonic acid levels in our cohort versus several large published studies 10,11,16–20 demonstrated lower total plasma homocysteine and methylmalonic acid levels in our cohort as compared to these previously published studies (Figures 2a, Figure 2c) whereas methionine levels were comparable (not shown). The high frequency of the c.482G>A(p.Arg161Gln) pathogenic variant in our cohort contributes to this observation as 13/27 (48%) of our individuals are compound heterozygous for this variant compared to 4/86 (5%) individuals in these published studies (combined) 8, 9, 14–18 .…”

Section: Resultssupporting

confidence: 55%

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Milder clinical and biochemical phenotypes associated with the c.482G > A (p.Arg161Gln) pathogenic variant in cobalamin C disease: Implications for management and screening

Almannai

Marom

Divin

et al. 2017

Molecular Genetics and Metabolism

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Introduction Cobalamin C disease is a multisystemic disease with variable manifestations and age of onset. Genotype-phenotype correlations are well-recognized in this disorder. Here, we present a large cohort of individuals with cobalamin C disease, several of whom are heterozygous for the c.482G>A pathogenic variant (p.Arg161Gln). We compared clinical characteristics of individuals with this pathogenic variant to those who do not have this variant. To our knowledge, this study represents the largest single cohort of individuals with the c.482G>A (p.Arg161Gln) pathogenic variant. Methods A retrospective chart review of 27 individuals from 21 families with cobalamin C disease who are followed at our facility was conducted. Results 13 individuals (48%) are compound heterozygous with the c.482G>A (p.Arg161Gln) on one allele and a second pathogenic variant on the other allele. Individuals with the c.482G>A (p.Arg161Gln) pathogenic variant had later onset of symptoms and easier metabolic control. Moreover, they had milder biochemical abnormalities at presentation which likely contributed to the observation that 4 individuals (31%) in this group were missed by newborn screening. Conclusion The c.482G>A (p.Arg161Gln) pathogenic variant is associated with milder disease. These individuals may not receive a timely diagnosis as they may not be identified on newborn screening or because of unrecognized, late onset symptoms. Despite the milder presentation, significant complications can occur, especially if treatment is delayed.

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Section: Resultssupporting

confidence: 55%

“…One of the observations in this study is that those in our cohort have lower total plasma homocysteine and methylmalonic acid levels compared to several published studies 10,11,16–20 . The high frequency of the c.482G>A (p.R161Q) pathogenic variant in this study contributes to this observation.…”

Section: Discussionsupporting

confidence: 50%

Milder clinical and biochemical phenotypes associated with the c.482G > A (p.Arg161Gln) pathogenic variant in cobalamin C disease: Implications for management and screening

Almannai

Marom

Divin

et al. 2017

Molecular Genetics and Metabolism

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“…Only two articles have reported a higher incidence of MMA than the current study. Han et al reported the incidence of MMA in Shandong Province, China as 1/3920. Guo et al reported the incidence of MMA in Jining, China as 1/3220.…”

Section: Discussionmentioning

confidence: 99%

Expanded newborn screening for inborn errors of metabolism by tandem mass spectrometry in newborns from Xinxiang city in China

Guo

Zhang

et al. 2020

Clinical Laboratory Analysis

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Abbreviations: HPA, hyperphenylalaninemia; IEM, inborn errors of metabolism; IVA, isovaleric academia; MMA, methylmalonic academia; MS/MS, tandem mass spectrometry; MSUD, maple syrup urine disease; PCD, primary carnitine deficiency; SCAD, short-chain acyl-CoA dehydrogenase deficiency. AbstractBackground: Tandem mass spectrometry is a powerful technology available in China over the last 15 years. The development of tandem mass spectrometry had made it possible to rapidly screen newborns for inborn errors of metabolism. The aim of this study was to determine the birth incidence of inborn errors of metabolism through expanded screening of newborns by tandem mass spectrometry in Xinxiang area.Methods: Dried blood spots from 50 112 newborns were assessed for inborn errors of metabolism by tandem mass spectrometry. The diagnoses were confirmed based on the clinical features, conventional laboratory tests, and the organic acid levels tested in urine by gas chromatography-mass spectrometry. Results:The study findings revealed that 31 newborns were diagnosed with inborn errors of metabolism. The total incidence rate of inborn errors of metabolism was 1/1617, and these included 16 cases of amino acid disorders (51.6%), nine cases of organic acid disorders (29.0%), and 6 (19.4%) cases of fatty acid beta-oxidation disorders. Conclusions:The screening for the incidence of inborn errors of metabolism in Xinxiang area showed that the rate was higher than previously reported. This study provides valuable data which may be useful in facilitating improvements in the expansion of screening to enable early diagnosis and treatment of inborn errors of metabolism before the onset of symptoms. K E Y W O R D S amino acid disorders, fatty acid beta-oxidation disorders, inborn errors of metabolism, organic acid disorders, tandem mass spectrometry S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section.

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“…[61] and according to Han et al (2015), the incidence of cblC was approximately 1:3,920 in Shandong Province, China. [62] In 1969, the first case was reported by Mudd et al, concerning an infant with homocystinuria, methylmalonic aciduria, cystathioninemia, and hypomethioninemia. The infant died at 7.5 weeks of age.…”

Section: Clinical Picturementioning

confidence: 99%

Three Main Causes of Homocystinuria: CBS, cblC and MTHFR Deficiency. What do they Have in Common?

Hoss

Poloni

Blom³

et al. 2019

J. inborn errors metab. screen.

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Genetic homocystinurias are a group of inborn errors of metabolism that result in the massive excretion of homocysteine (Hcy) in the urine due to Hcy accumulation in the body, usually causing neurological and cardiovascular complications. The three most frequent causes are classical homocystinuria [deficiency of cystathionine beta-synthase (CBS)], methylmalonic aciduria with homocystinuria, cblC type (cblC deficiency) and severe methylenetetrahydrofolate reductase (MTHFR) deficiency. In this review, we highlight the similarities and differences among these disorders. Briefly, their joint manifestation is the accumulation of tHcy, however, the other sulfur amino acids show various and even invers profiles. Vascular disease, developmental delay and seizures are found in all homocystinurias, nevertheless, the complications of CNS differ in a wide variety of presentations and severities and are apparently less pronounced in CBS deficiency. Moreover, patients with remethylation defects typically do not present ectopia lentis and bone disturbances, tall stature and osteoporosis. Whereas hematological alterations, such as megaloblastic anemia, thrombocytopenia neutropenia and life-threatening microangiopathy, are specific findings of cblC deficiency.

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Clinical presentation, gene analysis and outcomes in young patients with early-treated combined methylmalonic acidemia and homocysteinemia (cblC type) in Shandong province, China

Cited by 50 publications

References 17 publications

Milder clinical and biochemical phenotypes associated with the c.482G > A (p.Arg161Gln) pathogenic variant in cobalamin C disease: Implications for management and screening

Milder clinical and biochemical phenotypes associated with the c.482G > A (p.Arg161Gln) pathogenic variant in cobalamin C disease: Implications for management and screening

Expanded newborn screening for inborn errors of metabolism by tandem mass spectrometry in newborns from Xinxiang city in China

Three Main Causes of Homocystinuria: CBS, cblC and MTHFR Deficiency. What do they Have in Common?

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