Lactic acidosis with necrotizing encephalopathy in two sibs

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...

Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...

DefinitionDiabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus, characterized by a triad of hyperglycemia (blood glucose >250 mg/dL), ketonemia or ketonuria, and metabolic acidosis (arterial pH <7.30 and serum bicarbonate <18 mEq/L). It results from insulin deficiency combined with elevated levels of counterregulatory hormones—glucagon, catecholamines, cortisol, and growth hormone—leading to increased lipolysis, hepatic ketone production, and...

Diabetic ketoacidosis (DKA) is a metabolic emergency characterized by hyperglycemia, ketonemia, and metabolic acidosis. It results from severe insulin deficiency and an excess of counterregulatory hormones, leading to uncontrolled lipolysis, ketogenesis, and widespread electrolyte and fluid disturbances.Pathophysiology The central event in DKA is a profound loss of insulin action. Without insulin, glucose uptake in insulin-dependent tissues is impaired, while hepatic glucose production...

Encephalitis is inflammation of the brain parenchyma caused by direct viral invasion or immune-mediated mechanisms triggered by infections or tumors. Both processes lead to neuronal injury, disrupted neurotransmission, and diverse neurological symptoms, often with overlapping clinical and pathological features.Autoimmune EncephalitisIn autoimmune encephalitis, antibodies target neuronal antigens on cell surfaces, synapses, or within neurons. A key example is anti-NMDAR encephalitis, which can...

DefinitionHepatic encephalopathy is a reversible neurologic syndrome that results from advanced liver dysfunction or portosystemic shunting. It leads to disturbances in cognition, behavior, and motor function due to the brain’s exposure to gut-derived toxins that the liver fails to detoxify.EtiologyThis condition develops either in the setting of acute fulminant hepatitis or progressively during chronic liver disease, such as cirrhosis and portal hypertension. Portosystemic shunting—including...