Intrahepatic Cholestasis Is a Clinically Significant Feature Associated with Natural History of X-Linked Myotubular Myopathy (XLMTM): A Case Series and Biopsy Report.

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy characterized by profound skeletal muscle weakness, respiratory distress, and motor dysfunction. However, pathology is not limited to muscle and can be associated with life-threatening hepatic peliosis. Hepatobiliary disease has been reported in up to 17% of XLMTM patients but has not been extensively characterized. We report on five XLMTM patients who experienced intrahepatic cholestasis in their disease natural history, illustrating the need to further investigate these manifestations. These patients shared presentations that included pruritus, hypertransaminemia, and hyperbilirubinemia with normal gamma-glutamyl transferase, following infection or vaccination. Three patients who had genetic testing showed no evidence of genetic mutations associated with familial cholestasis. In one patient, progression to cirrhotic, decompensated liver disease occurred. Further investigations into the molecular pathomechanism underpinning these clinical observations in XLMTM patients will be important for informing patient care.

Broadening the spectrum of neonatal hemochromatosis.

Neonatal hemochromatosis (NH) has been defined as neonatal liver disorder accompanied by extrahepatic siderosis, and gestational alloimmune liver disease (GALD) is the main cause of NH. We report an atypical case of NH that may have gone underdiagnosed. A male infant was born at term after an uneventful antenatal period. At 7 h of life, he was noted to be tachypneic. Chest X-ray was normal and capillary blood gas analysis showed severe lactic acidosis. An extended blood test showed elevated levels of tyrosine and methionine that, after excluding an inborn error of metabolism, led to the diagnosis of acute liver failure. Hyperferritinemia and elevated transferrin saturation were suggestive of NH. Extrahepatic siderosis on MRI confirmed the diagnosis of NH, so even though the infant was in good general condition, a dose of intravenous immunoglobulin was administered and double volume exchange transfusion was performed. Treatment of a suspected case of GALD and prevention in subsequent gestations is imperative.

The Role of Liver Transplantation in Propionic Acidemia.

Despite optimal medical treatment and strict low-protein diet, the prognosis of propionic acidemia (PA) patients is generally poor. We aim to report our experience with liver transplantation (LT) in the management of PA patients. Six patients with PA received a LT at a mean age of 5.2 years (1.3-7.5 years). The indications for LT were frequent metabolic decompensations in the first 4 patients and preventative in the last 2 patients. Two patients presented hepatic artery thromboses that were solved through an interventional radiologist approach. These patients showed a very high procoagulant state that was observed by thromboelastography. Arterial vasospasm without thrombus was observed in 2 patients during the LT surgery. In order to avoid hepatic artery thrombosis, an arterial conduit from the recipient aorta to the hepatic artery of the donor was used in the fifth patient. After LT, patients presented improvement in propionyl byproducts without complete normalization, but no decompensations have been observed. In conclusion, LT could be a good therapeutic option to improve the metabolic control and the quality of life of PA patients. Improved surgical strategies along with new techniques of interventional radiology allow us to perform the LT minimizing the complications derived from the higher risk of hepatic artery thrombosis.