Citrin deficiency mimicking mitochondrial depletion syndrome
- PDF / 580,487 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 61 Downloads / 204 Views
CASE REPORT
Open Access
Citrin deficiency mimicking mitochondrial depletion syndrome S. C. Grünert1* , A. Schumann1, P. Freisinger2, S. Rosenbaum-Fabian1, M. Schmidts1, A. J. Mueller3, S. Beck-Wödl3, T. B. Haack3,4, H. Schneider1, H. Fuchs1, U. Teufel1, G. Gramer5, L. Hannibal6 and U. Spiekerkoetter1
Abstract Background: Neonatal intrahepatic cholestasis caused by citrin deficiency (CD) is a rare inborn error of metabolism due to variants in the SLC25A13 gene encoding the calcium-binding protein citrin. Citrin is an aspartate-glutamate carrier located within the inner mitochondrial membrane. Case presentation: We report on two siblings of Romanian-Vietnamese ancestry with citrin deficiency. Patient 1 is a female who presented at age 8 weeks with cholestasis, elevated lactate levels and recurrent severe hypoglycemia. Diagnosis was made by whole exome sequencing and revealed compound heterozygosity for the frameshift variant c.852_855del, p.Met285Profs*2 and a novel deletion c.(69 + 1_70–1)_(212 + 1_231–1)del in SLC25A13. The girl responded well to dietary treatment with a lactose-free, MCT-enriched formula. Her younger brother (Patient 2) was born 1 year later and also found to be carrying the same gene variants. Dietary treatment from birth was able to completely prevent clinical manifestation until his current age of 4.5 months. Conclusions: As CD is a well-treatable disorder it should be ruled out early in the differential diagnosis of neonatal cholestasis. Due to the combination of hepatopathy, lactic acidosis and recurrent hypoglycemia the clinical presentation of CD may resemble hepatic mitochondrial depletion syndrome. Keywords: Citrin deficiency, Neonatal cholestasis, Hypoglycemia, Newborn screening, Urea cycle defect, SLC25A13
Background Citrin deficiency (CD) is an autosomal recessive inborn error of metabolism caused by variants in the SLC25A13 gene [1–3]. Citrin is an aspartate-glutamate carrier located within the inner mitochondrial membrane and mainly expressed in the liver, kidney, heart and small intestine [4, 5]. Its role to transport aspartate from the mitochondrial matrix to the cytosol is important for several metabolic pathways including protein, nucleotide and urea synthesis as well as gluconeogenesis from lactate and the translocation of cytosolic NADH reducing equivalents into the mitochondria via the malate* Correspondence: [email protected] 1 Department of General Paediatrics, Adolescent Medicine and Neonatology, Medical Centre-University of Freiburg, Faculty of Medicine, Mathildenstraße 1, 79106 Freiburg, Germany Full list of author information is available at the end of the article
aspartate shuttle [4]. While CD is relatively common in East Asian populations, especially in Japan, the incidence in Europe is extremely low [2], although CD is a panethnic disease, and subjects have been reported from different ethnicities [6–10]. Three age-dependent clinical phenotypes are associated with CD, namely 1) neonatal intrahepatic cholestasis caused by citrin deficiency (NICC
Data Loading...
