1/79. Transcobalamin II deficiency with methylmalonic aciduria in three sisters. Transcobalamin II (TC II) is a plasma protein that binds vitamin B12 (cobalamin, Cbl) and facilitates cellular Cbl uptake by receptor-mediated endocytosis. In autosomal recessive TC II deficiency, intracellular Cbl deficiency results in an early onset of megaloblastic anaemia that may be accompanied by neurological abnormalities. Inadequate treatment may lead to neurological abnormalities. We describe three sisters, the daughters of first cousins of Moroccan origin, with TC II deficiency requiring continuous and long-term vitamin B12 treatment. The diagnosis was suspected from the finding of low unsaturated vitamin B12 binding capacity and confirmed by absence of detectable TC II by radioimmunoassay and by inability of cultured fibroblasts to synthesize TC II. ( info) |
2/79. Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate. A patient with severe pyruvate carboxylase deficiency presented at age 11 weeks with metabolic decompensation after routine immunization. She was comatose, had severe lactic acidemia (22 mM) and ketosis, low aspartate and glutamate, elevated citrulline and proline, and mild hyperammonemia. head magnetic resonance imaging showed subdural hematomas and mild generalized brain atrophy. biotin-unresponsive pyruvate carboxylase deficiency was diagnosed. To provide oxaloacetate, she was treated with high-dose citrate (7.5 mol/kg(-1)/day(-1)), aspartate (10 mmol/kg(-1)/day(-1)), and continuous drip feeding. Lactate and ketones diminished dramatically, and plasma amino acids normalized, except for arginine, which required supplementation. In the cerebrospinal fluid (CSF), glutamine remained low and lysine elevated, showing the treatment had not normalized brain chemistry. Metabolic decompensations, triggered by infections or fasting, diminished after the first year. They were characterized by severe lactic and ketoacidosis, hypernatremia, and a tendency to hypoglycemia. At age 3(1/2) years she has profound mental retardation, spasticity, and grand mal and myoclonic seizures only partially controlled by anticonvulsants. The new treatment regimen has helped maintain metabolic control, but the neurological outcome is still poor. ( info) |
3/79. Treatment of acquired epileptic aphasia with the ketogenic diet. Acquired epileptic aphasia remains a poorly understood entity, which is frequently difficult to treat. Previously described treatment modalities have included antiepileptic drugs, corticosteroids, intravenous immunoglobulin, and multiple subpial transections. We describe three patients with acquired epileptic aphasia refractory to traditional treatments who were successfully treated with the ketogenic diet. All three patients had lasting improvement of their language, behavior, and seizures for 26, 24, and 12 months, respectively. This is the first reported series of patients with acquired epileptic aphasia successfully treated with the ketogenic diet, and suggests a new therapeutic alternative for patients with this often difficult-to-treat disorder. ( info) |
| The ketogenic diet is an effective treatment for epilepsy in children. At Johns Hopkins Hospital more than 400 children have been placed on the ketogenic diet. The implementation and maintenance of this treatment require significant collaboration between the family and epilepsy Team. During initiation of the diet, in the hospital, parents attend classes on the history and mechanism of the diet, preparation of meals, psychological issues, complications and the management of childhood illnesses on the ketogenic diet. Many factors are considered in calculating a ketogenic formula. Age, weight, height and activity level are the obvious factors. However, secondary medical diagnoses, medications, neurological deficits, feeding issues and psychological issues are additional factors that affect the formulation of an optimal ketogenic prescription. Once this prescription has been formulated and implemented, many patients require fine-tuning of their ketogenic diets to get the best antiepileptic results while promoting growth. We believe that our success in sustaining this treatment is related to our fine-tuning and management practices. ( info) |
| A patient with 2-oxoadipic aciduria and 2-aminoadipic aciduria presented at 2 years of age with manifestations typical of organic acidemia, episodes of ketosis and acidosis, progressive to coma. This resolved and the key metabolites disappeared from the urine and blood. At 9 years of age she developed typical kearns-sayre syndrome with complete heart block, retinopathy, and ophthalmoplegia. Southern blot revealed a deletion in the mitochondrial genome. ( info) |
6/79. Hyperglycinemia and propionyl coA carboxylase deficiency and episodic severe illness without consistent ketosis. Propionyl CoA carboxylase deficiency was found in a 7-month-old boy who presented with attacks of vomiting, anorexia, weight loss, weakness, and hypotonia. He failed to thrive and had generalized seizures. He had propionic acidemia and hyperglycinemia; these are the manifestations of the ketotic hyperglycinemia syndrome. However, ketonuria was not a consistent part of his clinical picture, and he had at least two episodes of acute overwhelming illness, the latter one fatal, in which ketones were never found in the urine. Large amounts of pyrrolidone carboxylic acid were found in body fluids. ( info) |
| Turner's syndrome is a condition involving total or partial absence of one x chromosome and has been associated with a number of diseases including non insulin dependent diabetes mellitus, abnormalities of glucose metabolism and hypothreosis. There have been many case reports in which Turner's syndrome is associated with type 2 diabetes, but the association with type 1 diabetes and/or life threatening complications is very rare. We present an unusual case of a patient with Turner's syndrome who has type 1 diabetes and is complicated with ketoacidosis, severe acute and recurrent pulmonary edema and rhabdomyolysis. ( info) |
8/79. hypoglycemia and resistance to ketoacidosis in a subject without functional insulin receptors. humans with congenital absence of the islets of langerhans and mice rendered null for the insulin receptor rapidly develop severe hyperglycemia and ketoacidosis and, if untreated, die in the early neonatal period. In contrast, children with homozygous or compound heterozygous mutations of the insulin receptor gene, although hyperglycemic postprandially, survive for many months without developing ketoacidosis. Paradoxically, they often develop hypoglycemia. The rarity of the condition and the difficulties of undertaking metabolic studies in ill infants have limited the physiological information that might explain the clinical features. We studied a boy with Donohue's syndrome who represents a further example of the null phenotype, with two different and novel nonsense mutations in the alpha-subunit of the receptor. He survived for 8 months without developing ketoacidosis, and fasting hypoglycemia was a frequent problem. Despite the complete absence of insulin receptors, evidence for persistent insulin-like effects on fat and liver was seen; fasting plasma beta-hydroxybutyrate and nonesterified fatty acid levels were low, fell further during the early postprandial period, and failed to rise in response to hypoglycemia. The inverse relationships between plasma insulin and insulin-like growth factor-binding protein-1 levels were maintained, suggesting persistent hepatic effects of insulin. GH levels measured over a 6.5-h period were low throughout. Thus, the differences between congenital insulin deficiency vs. insulin receptor deficiency in humans may be explained by persistent insulinomimetic activity of the grossly elevated plasma insulin presumably being mediated through the type 1 insulin-like growth factor receptor. As GH plays a critical role in the regulation of ketogenesis during insulinopenia in humans, but not in rodents, this may contribute to the distinct phenotype of human vs. mouse insulin receptor knockouts. ( info) |
| glycogen synthase deficiency is a rare inborn error of metabolism, characterized by fasting hypoglycemia, hypoglycemic seizures, and ketonuria. Only 7 families with 14 affected children have been reported. Here, we report an additional patient with this deficiency. Findings in this patient were clinically and biochemically consistent with those reported in patients with ketotic hypoglycemia and may alert the clinician to consider glycogen synthase deficiency. ( info) |
| epilepsia partialis continua (EPC) may occur during nonketotic hyperglycemia but has not been described with diabetic ketoacidosis. The authors report a patient with EPC associated with ketotic hyperglycemia. Brain MRI showed two areas of abnormal signal intensity in the left precentral gyrus and in the right cerebellar hemisphere. hyperglycemia may reduce seizure threshold because of the increase in gamma-aminobutyric acid metabolism and may trigger epileptic discharges. ( info) |