Citrin deficiency mimicking mitochondrial depletion syndrome.

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.

Indications for pediatric liver transplantation. Data from the Heidelberg pediatric liver transplantation program.

Nowadays liver transplantation is an established treatment for children with end-stage liver disease with very good 1- and 5-year survival. This has been achieved through constant improvement of surgical techniques, new immunosuppressive drugs and clinical management. Indications for liver transplantation in infants and children include acute liver failure (ALF), chronic liver failure with pruritus, complications of cholestasis and failure to thrive. In young children, the most common liver disease leading to transplantation is biliary atresia. Biliary atresia accounts for at least 50 percent of all liver transplants in children and is characterized by the failure of the bile ducts to develop normally and drain bile from the liver. Several models to assess prognosis of liver disease have been developed. In acute liver failure leukocyte count, bilirubin, International Normalized Ratio (INR) and age have a strong correlation with outcome. In chronic liver failure, PELD (Pediatric end-stage liver disease) Score and the occurrence of complications of liver disease are important prognostic tools. Since the start of our own paediatric liver transplantation program at the University of Heidelberg in 2003, already 15 Children between 5 months and 14 years have been transplanted. Indications and outcome of these patients are reviewed in this paper.

[Lethality in children with neuroblastoma (author's transl)]. / Die Letalität bei Kindern mit Neuroblastom - Ein Vergleich von zwei 10-Jahresstudien aus der pädiatrischen Onkologie der Universität Tübingen.

32 cases of sympathetic nervous system tumours have been treated in a single pediatric oncologic center during 1970-79 and have been submitted to a follow-up analysis according to the known prognostic parameters. A high significance of prognostic staging is seen in correlation to age, stage, site of the primary, histologic differentiation, postoperative excretion of metabolic catecholamines and surgical radicality. The overall lethality in this material has been 38%, in contrast to a lethality rate of 72% in the same center during the preceding period (1960-69). The reason for this notable drop is thought to be early diagnosis leading to a combination of favourable prognostic parameters. Total surgical removal of the primary is considered the most important therapeutic factor, being exclusively sufficient in cases where the prognosis is favourable (first year of life, stage I and II). A long term lethality rate subsequent to cytotoxic treatment has been observed, so that the 2-years-survival time has to be discussed.