Evidence of cataplerosis in a patient with neonatal classical galactosemia presenting as citrin deficiency

2008 ◽  
Vol 48 (3) ◽  
pp. 517-522 ◽  
Author(s):  
François Feillet ◽  
Marc Merten ◽  
Shyue-Fang Battaglia-Hsu ◽  
Daniel Rabier ◽  
Keiko Kobayashi ◽  
...  
Keyword(s):  
Classical Galactosemia ◽  
Citrin Deficiency

scholarly journals Deep phenotyping classical galactosemia: clinical outcomes and biochemical markers

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Mendy M Welsink-Karssies ◽  
Sacha Ferdinandusse ◽  
Gert J Geurtsen ◽  
Carla E M Hollak ◽  
Hidde H Huidekoper ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Newborn Screening ◽  
Clinical Outcomes ◽  
Movement Disorders ◽  
Brain Mri ◽  
Primary Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Classical Galactosemia ◽  
Intellectual Outcome

Abstract Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 ± 14) and was <85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N-glycan peaks were found between controls and patients. However, no significant differences in either N-glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome < 85) and normal intellectual outcome (intellectual outcome ≥ 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and currently no long-term complications, demonstrated significantly lower galactose-1-phospate levels than classical patients (P < 0.0005). Qualitative analysis of the MRI’s demonstrated brain abnormalities in 18 of the 21 patients, more severely in patients with a lower intellectual outcome and/or with movement disorders. This study demonstrates a large variability in clinical outcome, which varies from a below average intelligence, movement disorders and in females primary ovarian insufficiency to a normal clinical outcome. In our cohort of classical galactosemia patients, galactose-1-phosphate levels and N-glycan variations were not associated with clinical outcomes, but galactose-1-phosphate levels did differentiate between classical and variant patients detected by newborn screening. The correlation between brain abnormalities and clinical outcome should be further investigated by quantitative analysis of the MR images. The variability in clinical outcome necessitates individual and standardized evaluation of all classical galactosemia patients.

Combining newborn metabolic and genetic screening for neonatal intrahepatic cholestasis caused by citrin deficiency

2019 ◽  
Vol 43 (3) ◽  
pp. 467-477 ◽  
Author(s):  
Yiming Lin ◽  
Yaru Liu ◽  
Lin Zhu ◽  
Kaixing Le ◽  
Yuyan Shen ◽  
...  
Keyword(s):  
Genetic Screening ◽  
Intrahepatic Cholestasis ◽  
Citrin Deficiency

Novel diagnostic approach to citrin deficiency: Analysis of citrin protein in lymphocytes

2007 ◽  
Vol 90 (1) ◽  
pp. 30-36 ◽  
Author(s):  
Daisuke Tokuhara ◽  
Mikio Iijima ◽  
Akiko Tamamori ◽  
Toshihiro Ohura ◽  
Junji Takaya ◽  
...  
Keyword(s):  
Diagnostic Approach ◽  
Citrin Deficiency

scholarly journals Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency in Korean Infants

2007 ◽  
Vol 22 (6) ◽  
pp. 952
Author(s):  
Jae Sung Ko ◽  
Jung Han Song ◽  
Sung Sup Park ◽  
Jeong Kee Seo
Keyword(s):  
Intrahepatic Cholestasis ◽  
Citrin Deficiency

scholarly journals Cholesterol Metabolism Is Enhanced in the Liver and Brain of Children With Citrin Deficiency

2018 ◽  
Vol 103 (7) ◽  
pp. 2488-2497 ◽  
Author(s):  
Satoshi Hirayama ◽  
Hironori Nagasaka ◽  
Akira Honda ◽  
Haruki Komatsu ◽  
Takahiro Kodama ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Density Lipoprotein ◽  
Normal Liver ◽  
Serum Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Control Group ◽  
Healthy Children ◽  
Citrin Deficiency ◽  
Deficient Group

Abstract Context Citrin-deficient infants present neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), which resolves at 12 months. Thereafter, they have normal liver function associated with hypercholesterolemia, and a preference for lipid-rich carbohydrate-restricted diets. However, some develop adult-onset type II citrullinemia, which is associated with metabolic abnormalities. Objectives To identify the causes of hypercholesterolemia in citrin-deficient children post-NICCD. Design and Setting We determined the concentrations of sterol markers of cholesterol synthesis, absorption, and catabolism by liquid chromatography–electrospray ionization–tandem mass spectrometry and evaluated serum lipoprotein profiles. Subjects Twenty citrin-deficient children aged 5 to 13 years and 37 age-matched healthy children. Intervention None. Main Outcome Measures Relationship between serum lipoproteins and sterol markers of cholesterol metabolism. Results The citrin-deficient group had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than did the control group (78 ± 11 mg/dL vs 62 ± 14 mg/dL, P < 0.001), whereas the two groups had similar low-density lipoprotein cholesterol and triglyceride concentrations. The concentrations of markers of cholesterol synthesis (lathosterol and 7-dehydrocholesterol) and bile acids synthesis (7α-hydroxycholesterol and 27-hydroxycholesterol) were 1.5- to 2.8-fold and 1.5- to 3.9-fold, respectively, higher in the citrin-deficient group than in the control group. The concentration of 24S-hydroxycholesterol, a marker of cholesterol catabolism in the brain, was 2.5-fold higher in the citrin-deficient group. In both groups, the HDL-C concentration was significantly positively correlated with that of 27-hydroxycholesterol, the first product of the alternative bile acid synthesis pathway. Conclusions HDL-C and sterol marker concentrations are elevated in citrin-deficient children post-NICCD. Moreover, cholesterol synthesis and elimination are markedly enhanced in the liver and brain of citrin-deficient children.

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