X-linked myopathy with excessive autophagy (XMEA) is a rare childhood onset disease characterized by slow progressive vacuolation and atrophy of skeletal muscle. There is no known cardiac or intellectual involvement. Presentation
The incidence of this disease is not precisely known but it is considered to be rare (< 1/106 population). It has been reported in 15 families to date mostly from Canada, Finland and France.This disease usually presents between the ages of 5 to 10 years old. The usual picture is with weakness involving the upper legs and affects activities such as running and climbing stairs. As the condition progresses, patients tend to experience weakness in their lower legs and arms. Some remain able to walk in advanced age, while others require assistance in adulthood. Genetics
This disorder is inherited in a recessive X linked fashion. As a result, males are much more commonly affected than females. It is due to a mutation in VMA21 gene - the human homolog of the yeast Vma21p protein. This gene is located on the long arm of chromosome X (Xq28). It is an essential assembly chaperone of the vacuolar ATPase - the principal mammalian proton pump complex. Mutations in this gene increase lysosomal pH. This in turn reduces lysosomal degradative ability and blocks autophagy. Pathology
The muscle fibers are rarely necrotic but have evidence of excessive autophagic activity and exocytosis of the phagocytosed material. They have increased variation in size and are predominantly composed of round small and hypertrophic fibers.
When gastric varices are symptomatic, however, they usually present acutely and dramatically with upper gastrointestinal bleeding. The symptoms can include vomiting blood, melena (passing black, tarry stools); or passing maroon stools or frank blood in the stools. Many people with bleeding gastric varices present in shock due to the profound loss of blood.Secondly, patients with acute pancreatitis may present with gastric varices as a complication of a blood clot in the splenic vein. The splenic vein sits over the pancreas anatomically, and inflammation or cancers of the pancreas may result in a blood clot forming in the splenic vein. As the short gastric veins of the fundus of the stomach drain into the splenic vein, thrombosis of the splenic vein will result in increased pressure and engorgement of the short veins, leading to varices in the fundus of the stomach.Laboratory testing usually shows low red blood cell count and often a low platelet count. If cirrhosis is present, there may be coagulopathy manifested by a prolonged INR; both of these may worsen the bleeding from gastric varices.In very rare cases, gastric varices are caused by splenic vein occlusion as a result of the mass effect of slow-growing pancreatic neuroendocrine tumors. Diagnosis
Diagnosis of gastric varices is often made at the time of upper endoscopy. Classification
The Sarin classification of gastric varices identifies four different anatomical types of gastric varices, which differ in terms of treatment modalities. Treatment
Initial treatment of bleeding from gastric varices focuses on resuscitation, much as with esophageal varices.