The natural history of classic galactosemia: lessons from the GalNet registry.

BACKGROUND: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. METHODS: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. RESULTS: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. CONCLUSION: This study describes the natural history of classic galactosemia based on the hitherto largest data set.

Levetiractam in the treatment of two children with myoclonic status epilepticus.

Levetiracetam (LEV) is approved as second line treatment for partial onset seizures in adults and children older than four years of age. Recently, an intravenous formulation was developed as an alternative to standard oral medication. We report the successful treatment of two children suffering from myoclonic status epilepticus with intravenous LEV. Intravenous application of LEV was safe and not associated with significant side effects. In conclusion, intravenous application of LEV appears to be a further option in treatment of children with myoclonic status epilepticus.

An unusual case of intrauterine symptomatic neonatal liver failure.

UNLABELLED: We present an unusual case of neonatal liver failure. Isolated ascites was diagnosed in a female fetus at week 34 gestational age upon routine ultrasound. In the 35th week of gestation a cesarean section was carried out after puncture of fetal ascites. After birth the patient showed symptoms and complications of acute liver failure with portal hypertension. High serum ferritin concentrations, MRI findings compatible with tissue iron overload and no evidence for infectious disease or inborn errors of metabolism suggested possible neonatal hemochromatosis (NH). HFE gene mutation analysis studies of the child and parents were negative. An anti-oxidative and iron chelating therapy was introduced, followed by clinical stabilisation of the newborn and normalisation of liver function. The liver biopsy at 4 month of age showed mild fibrosis with a few iron-loaded hepatocytes and macrophages. At 2 years of age the child was virtually healthy. CONCLUSION: The clinical course of our patient indicates that the pathological changes in the liver being associated with presumptive NH may be reversible when NH is diagnosed early and antioxidative and chelating therapy is immediately initiated.