No abstract

Background Hyperammonemic encephalopathy in newborns with urea cycle disorders and certain organic acidurias can cause severe brain injury, coma and death. Standard therapy includes protein restriction, nitrogen-scavenging drugs, prevention of catabolism and hemodialysis. Neuroprotective hypothermia as part of the treatment has been reported only 3 times. It has been suggested that mild systemic hypothermia can contribute to better neurological outcomes in hyperammonemic encephalopathy. However, the limited experience precludes accurate conclusions on safety and efficacy. Methods Whole body therapeutic hypothermia was included in the standard treatment of hyperammonemic encephalopathy in 4 neonates with urea cycle disorder or organic aciduria. Results Two patients survived the initial crisis. One patient has a developmental quotient of 0.8, while the other shows severe developmental delay. The cooling protocol had to be discontinued in 3 patients due to the otherwise untreatable complications (hypotension and hemorrhage). Conclusion The efficacy and safety of therapeutic hypothermia in the treatment of neonatal hyperammonemic encephalopathy depend on various factors, requiring further evaluation.

The use of standardised risk scores allows selection of complex cardiac diseases, which may have very different outcomes in various centres. In our case, those with higher ABC scores were correctly identified and referred for treatment abroad. In this way, we allowed gradual progress of the cardiosurgical model in Croatia and maintained an enviably low mortality rate.

astrocytoma was diagnosed in 3 cases, 2 received treatment with mTOR inhibitor, and one child underwent VP shunt due to enlarging SEGA causing obstructive hydrocephalus. Six (55%) of the children with TSC suffered from epilepsy and psychomotoric development delay.Although CRs are benign from the cardiovascular standpoint, and have a natural history of spontaneous regression, their close association with TSC prompt for early prenatal diagnosis and family counselling regarding the dismal longterm prognosis. Recent literature suggests that early therapy with mTOR inhibitors may prevent the development of TS manifestations.

We report clinical course and genotype of four patients with hepatocerebral form of MDS.Patients 1 and 2, daughters of consanguineous Roma parents, presented with liver failure at six and two days of life, respectively. The older sibling had lactic acidosis and progressive liver failure, without clear neurological involvement. Liver histology revealed gigantocellular hepatitis, fibrosis, cholestasis, hemosiderosis and steatosis. Working diagnosis was neonatal hemosiderosis. Despite the treatment, disease progressed to death at 40 days. Younger sibling had similar clinical course and MDS was suspected. Immunohistochemical staining of the deceased sibling's liver showed combined respiratory chain deficiency. Homozygous variant in the DGUOK gene in both patients confirmed the diagnosis. Despite cofactor/antioxidant treatment, patient 2 died at the age of two months.Patient 3 presented with recurrent nonketotic hypoglycemia, cholestasis and hypotonia at the age of two months. Liver disease was slowly progressive, with permanently elevated lactate and alanine. Histology showed gigantocellular hepatitis, fibrosis, cholestasis, hemosiderosis, polymorphous mitochondria and microvesicular steatosis. MDS was suspected, but immunohistochemical staining was uninformative. Due to end-stage liver disease, LTx was performed at the age of six months. Patient died in early postoperative period. Whole exome sequencing (WES) revealed biallelic mutations in the MPV17 gene.Patient 4 had intrauterine growth retardation, severe hypotonia and developmental delay since birth. Acute liver failure, presenting with ketotic hypoglycemia, lactic acidosis, hepatomegaly and coagulopathy, occurred at the age of four months. The individual additionally developed nystagmus. Brain MRI was normal. Liver biopsy showed steatosis and abnormal mitochondria. Immunohistochemistry and clearly decreased mtDNA copy number per nuclear genome in liver pointed to MDS. The disease progressed rapidly and patient died three weeks after admission. WES revealed two biallelic mutations in the POLG gene.Revealing genetic basis of liver failure due to MDS, with WGS as an important option, is pre-requisite to decision on LTx. It is also essential for genetic counseling and prenatal diagnosis in future pregnancies.