Acetyl-CoA transporter 1 (AT-1) is a transmembrane protein which regulates influx of acetyl-CoA from the cytosol to the lumen of the endoplasmic reticulum and is therefore important for the posttranslational modification of numerous proteins. Pathological variants in the SLC33A1 gene coding for AT-1 have been linked to a disorder called Huppke-Brendel syndrome, which is characterized by congenital cataracts, hearing loss, severe developmental delay and early death. It has been described in eight patients so far, who all had the abovementioned symptoms together with low serum copper and ceruloplasmin concentrations. The link between AT-1 and low ceruloplasmin concentrations is not clear, nor is the complex pathogenesis of the disease. Here we describe a further case of Huppke-Brendel syndrome with a novel and truncating homozygous gene variant and provide novel biochemical data on N-acetylated amino acids in cerebrospinal fluid (CSF) and plasma. Our results indicate that decreased levels of many N-acetylated amino acids in CSF are a typical metabolic fingerprint for AT-1 deficiency and are potential biomarkers for the defect. As acetyl-CoA is an important substrate for protein acetylation, we Katarina Šiki c and Tessa M.A. Peters contributed equally to this study.Ron A. Wevers and Ivo Bari c contributed equally to this study.

ObjectivesHyperammonemia in a newborn is a serious condition, which requires prompt intervention as it can lead to severe neurological impairment and death if left untreated. The most common causes of hyperammonemia in a newborn are acute liver failure and inherited metabolic disorders. Several mitochondrial disorders have been described as a cause of severe neonatal hyperammonemia.Case presentationHere we describe a new case of adenosine-triphosphate (ATP) synthase deficiency due to m.8528T>C mutation as a novel cause of severe neonatal hyperammonemia. So far six patients with this mutation have been described but none of them was reported to need hemodialysis in the first days of life.ConclusionThis broadens the so far known differential diagnosis of severe neonatal hyperammonemia requiring hemodialysis.

regulated by a numerous enzymes that modify and transfer sugar residues to amino acid side chains.Over 150 different types of CDGs have been described. The most common are phosphomannomutase 2 (PMM2-CDG) and -1,3-glucosyltransferase deficiency (ALG6-CDG). Symptoms common to all CDGs are seizures, psychomotor delay, hypotonia, feeding disorders, liver disease and coagulopathy. Diagnosis is based on clinical presentation and sialotransferrin profiling and confirmed by gene analysis. Early diagnosis is critical in disorders for which specific therapy exists.Female infant was born from a third, uneventful pregnancy. Parents are not related and older siblings are healthy. Since birth, the infant was severely hypotonic and exhibited developmental delay, feeding disorder and failure to thrive. At the age of three months she was transferred to our Department for further work-up. At that time, she had low body weight (4314 g, 1.c) and was hypotonic with reduced spontaneous movements. We had noticed dysmorphic features-hypertelorism, micrognathia, abnormal ears, flattened nose, rhizomelic limbs, inverted mamillae and abnormal fat distribution. She was fed with elemental infant formula through the nasogastric tube. The patient had small intestine malrotation that manifested with recurrent vomiting which was resolved after surgical intervention. She developed thrombosis of the brain venous sinuses due to coagulopathy (low concentration of antithrombin III, protein C and coagulation factors IX and XI). She was also diagnosed with hypothyreosis and suffered from generalised oedema with hypoalbuminemia as a consequence of protein losing enteropathy, treated with albumin infusions. Protein losing enteropathy improved on elemental formula.Severe epilepsy was drug-resistant. Sialotransferrin profiling pointed towards a glycosylation defect (elevated di-sialotransferrins, lowered penta-and tetra-sialotransferrins). Gene analysis revealed biallelic mutations in the ALG6 gene, which codes for glycosilation enzyme -1,3-glucosyltransferase.ALG6-CDG has a recognizable phenotype characterised by hypotonia and proximal muscle weakness, extrapyramidal signs, pharmacoresistant epilepsy, coagulopathy, protein losing enteropathy and dysmorphic features. Described patients had poor prognosis. There is no specific therapy available. Early diagnosis is important to predict and treat symptoms and to stop diagnostic odyssey. It enables prenatal diagnostics in future pregnancies.