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A new amino acid formulation and a variety of treatment products incorporating it were evaluated for long-term safety, efficacy, and acceptance in 25 subjects with phenylketonuria over a period of 5 years. Palatability of the treatment was improved by reducing the required intake of amino acids, reformulating the mixture to have better taste, and providing vitamins and minerals as tablets. The hypotheses were that these strategies would improve compliance and metabolic control and maintain nutritional status in subjects. Compliance with treatment was determined from mean reported intakes (4-day diet records) and from mean ‘received’ intakes using receipts of treatment products actually shipped to individuals upon request. Mean amino acid intakes prescribed were significantly reduced from study entry to end, from 1.2 g/kg to 0.7 g/kg (p < 0.001). Reported intakes were similarly reduced from 1.3 g/kg to 0.7 g/kg (p < 0.001). While actually ‘received’ intakes of amino acid formula were also significantly reduced (p < 0.001), intakes by this measure were much lower than either prescribed or reported, 0.9 g/kg at entry and 0.4 g/kg at the end of the study, suggesting that acceptance of the treatment (usage of products), even when made more palatable, is below clinical expectations. In spite of these findings, mean serum proteins and minerals, height and weight were not significantly reduced during the study, supporting the safety of lowered intakes of amino acids and of nutritionally incomplete products. While the increase in mean serum phenylalanine concentration from 0.38 to 0.48 mmol/L was significant (p < 0.03), this mean rise of 0.1 mmol/L during a corresponding mean age increase of 4.2 years (from 6.9 to 11.1 years) is lower than in other recent reports from longitudinal studies of outcomes during this age range in subjects treated with traditional products. These data support the safety and efficacy of a more palatable and flexible approach to treatment.

Inborn errors of the pyruvate dehydrogenase complex (PDC) are associated with lactic acidosis, neuroanatomic defects, developmental delay, and early death. PDC deficiency is a clinically heterogeneous disorder, with most mutations located in the coding region of the X-linked α subunit of the first catalytic component, pyruvate dehydrogenase (E 1 ). Treatment of E 1 deficiency has included cofactor replacement, activation of PDC with dichloroacetate, and ketogenic diets. In this report, we describe the outcome of ketogenic diet treatment in seven boys with E 1 deficiency. These patients were divided into two groups based on their mutations (R349H, three patients; and R234G, four patients, two sibling pairs). All seven patients received ketogenic diets with varying degrees of carbohydrate restriction. Clinical outcome was compared within each group and between siblings as related to the intensity and duration of dietary intervention. Subjects who either had the diet initiated earlier in life or who were placed on greater carbohydrate restriction had increased longevity and improved mental development. Based on the improved outcomes of patients with identical mutations, it appears that a nearly carbohydrate-free diet initiated shortly after birth may be useful in the treatment of E 1 deficiency.

Gluconeogenesis is defined as the net formation of glucose from non-carbohydrate precursors such as pyruvate, lactate, glycerol, and certain amino acids. It is crucial for survival because glucose, the primary substrate for a number of tissues, most notably the brain, is only available during feeding, and liver glycogen stores can only provide glucose for a few hours. Gluconeogenesis and glycolysis have many enzymes in common (Fig. 1). Exceptions are the enzymes that catalyze the four irreversible steps which ensure a unidirectional flux from pyruvate to glucose: Pyruvate carboxylase (PC) Phosphoenolpyruvate carboxykinase (PEPCK) Fructose-1,6-bisphosphatase (FBPase) Glucose-6-phosphatase (G-6-Pase)

The prenatal diagnosis of cystinosis is currently based on the increased amount of free-cystine present in amniotic fluid cells. Amniocyte cultures must be grown for at least 2 weeks to obtain sufficient cells for such measurements. Thus, the diagnosis cannot be made until close to 20 weeks gestational age by this method. We report a case in which chorionic villi were used for direct cystine measurement resulting in the in utero diagnosis of cystinosis at 9 weeks gestational age. The diagnosis was confirmed by the study of cultured chorionic villus cells, and of the 10-week abortus.

We describe the use and early results of the Oregon Public Health Laboratory computer to monitor hospital and practitioner compliance with state newborn screening recommendations. The system tracks five major categories of screening practice in which 21 types of errors affecting screening test quality have been identified. Our initial pilot study examined computer generated data for 23,717 specimens submitted by 116 Oregon birthing facilities over a four-month period. Results show that 58.3 per cent of newborn screening specimens were submitted incorrectly according to current state recommendations.

The co-existence of a hereditary defect of pyruvate carboxylase activity along with proximal renal tubular acidosis in several patients prompted the following theories: (1) Some of the bicarbonate which is normally reabsorbed from the glomerular filtrate is trapped in the mitochondria by pyruvate carboxylase in the conversion of pyruvate to oxaloacetate. The subsequent conversion of oxaloacetate to phosphoenol pyruvate releases CO2 in the cytosol. (2) The trapping of HCO-3 by pyruvate (or other carboxylases) provides an important route for the recovery of filtered HCO-3. (3) The process of trapping HCO-3 from the glomerular filtrate followed by release of CO2 in the cytosol contributes to the apparently high RQ of kidney, since the CO2 does not originate from a metabolic fuel. (4) Lactate and possibly other fuels are actively taken up by the kidney and are used as energy sources. Diversion of lactate for gluconeogenesis may contribute to the "excess substrate uptake" phenomenon. (5) It is possible that some of the glucose which is synthesized in the cortex is used for glycolysis in the medulla. Conversely, lactate produced in the medulla may be available to the cortex for bicarbonate trapping and thus for gluconeogenesis.

Four patients with hyperparathyroidism associated with myotonic dystrophy have been identified. All were females aged between 2 and 45 years. They were from three separate families, with two related patients being mother and daughter. In addition, one patient had medullary carcinoma of the thyroid and was diagnosed as having multiple endocrine adenomatosis, type 2A; another had an unspecified thyroid carcinoma; a third patient had neurofibromatosis. Our data suggest that myotonic dystrophy may somehow be associated with one or more of these disorders of neural crest origin.

Using stool samples previously obtained for a nutritional balance study of very small infants, the intake, excretion, and percent absorption (%A) of individual fatty acids were quantitated by gas-liquid chromatography in two groups of patients; one receiving a formula providing fat as long chain triglycerides (LCT), the other providing 40% fat as medium chain triglyceride (MCT). The total fat intake for each group was 7.22 g/kg/day (MCT group), 6.02 g/kg/day (LCT group) and the absorption was 6.79 g/kg/day (MCT group) and 5.41 g/kg/day (LCT group). The %A of individual acids was comparable in both groups being greater than 99% for MCT and being lowest (62%) for C18:0 FA. As a consequence, infants in the MCT-fed group had a better total %A of fat, 95.2 vs 89.9% and absorbed more fat than the LCT group.

A 5-month-old infant was found to have hypermethioninaemia (0.8 mumol/ml) that has persisted intermittently (0.02-1.3 mumol/ml) over a period of 3 years. She presented with developmental delay and failure to thrive associated with gross abuse and neglect. Histological examination of the liver revealed inflammation of the portal triads. The activity of hepatic L-methionine-S-adenosyltransferase (EC 2.5.1.6) was normal. Whether the biochemical findings were the cause or the result of the hepatic damage is uncertain, but the minimal histological findings in the liver suggest a primary biochemical defect.

Un medecin volontaire dans un camp de refugies dans le desert du Soudan compare son experience a celle faite quelques annees plus tot dans un camp de refugies en Thailande. Le camp actuel contient un hopital pour 35 adultes et une annexe pour 25 enfants, pour une population de 8700 refugies