The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency.

BACKGROUND: Dihydrolipoamide dehydrogenase (DLD lipoamide dehydrogenase, the E3 subunit of the pyruvate dehydrogenase complex (PDHC)) is the third catalytic enzyme of the PDHC, which converts pyruvate to acetyl-CoA catalyzed with the introduction of acetyl-CoA to the tricyclic acid (TCA) cycle. In humans, PDHC plays an important role in maintaining glycose homeostasis in an aerobic, energy-generating process. Inherited DLD-E3 deficiency, caused by the pathogenic variants in DLD, leads to variable presentations and courses of illness, ranging from myopathy, recurrent episodes of liver disease and vomiting, to Leigh disease and early death. Currently, there is no consensus on treatment guidelines, although one suggested solution is a ketogenic diet (KD). OBJECTIVE: To describe the use and effects of KD in patients with DLD-E3 deficiency, compared to the standard treatment. RESULTS: Sixteen patients were included. Of these, eight were from a historical cohort, and of the other eight, four were on a partial KD. All patients were homozygous for the D479V (or D444V, which corresponds to the mutated mature protein without the mitochondrial targeting sequence) pathogenic variant in DLD. The treatment with partial KD was found to improve patient survival. However, compared to a historical cohort, the patients' quality of life (QOL) was not significantly improved. CONCLUSIONS: The use of KD offers an advantage regarding survival; however, there is no significant improvement in QOL.

[Dietetic treatment with fructose in a 5-year-old girl with recurrent D-lactic acidosis]. / Tratamiento dietético con fructosa en una niña de 5 años con acidosis D-láctica recurrente.

D-lactic acidosis is an infrequent complication, mainly reported in patients with short bowel syndrome. It is characterized by recurrent episodes of encephalopathy with elevated serum D-lactic acid, usually associating metabolic acidosis. The presence of D-lactate-producing bacteria is necessary for the development of this complication. Other factors, such as the ingestion of large amounts of carbohydrates or reduced intestinal motility, contribute to D-lactic acidosis. We report a case of recurrent D-lactic acidosis in a 5-year-old girl with short bowel syndrome, due to a midgut volvulus. She initially received oral antibiotics in order to treat bacterial overgrowth, together with oral carbohydrates restriction. Nevertheless, recurrences did occur. Subsequently, 25% of the enteral nutrition was replaced for a formula containing fructose exclusively, while other fermentable sugars were restricted from the diet. After 16 years of follow up, further recurrences of D-lactic acidosis were not observed.

Severe lactic acidosis in an extremely low birth weight infant due to thiamine deficiency.

BACKGROUND: In this case report, we present a preterm newborn with persistent lactic acidosis who received total parenteral nutrition (TPN) that lacked thiamine. CASE PRESENTATION: A 28-week-old, 750 g female infant was born with an Apgar score of 8 at the 5th minute. Umbilical cord blood gas levels, including lactate level, were normal, and she was admitted to our neonatal intensive care unit (NICU). Achieving full enteral feeding was not possible due to gastric residues and abdominal distention, making the patient dependent on TPN during the first 2 weeks of life. An insidious increase in lactic acid levels and uncompensated metabolic acidosis were apparent from the 23rd day of life. Severe metabolic acidosis was persistent despite massive doses of bicarbonate. The acidosis resolved dramatically within 6 h when the patient was administered with thiamine. CONCLUSIONS: Although TPN is life saving in the NICU, meticulous attention must be paid to provide all essential macro- and micro-nutrients.

Tratamiento dietético con fructosa en una niña de 5 años con acidosis D-láctica recurrente / Dietetic treatment with fructose in a 5-year-old girl with recurrent D-lactic acidosis

La acidosis D-láctica es una patología infrecuente, habitualmente descrita en pacientes con síndrome de intestino corto. Se caracteriza por episodios recurrentes de encefalopatía con D-lactato sérico elevado y, generalmente, acidosis metabólica. Para su desarrollo es necesario el sobrecrecimiento de bacterias productoras de D-lactato en el colon. Otros factores, como la ingesta abundante de carbohidratos o la disminución de la motilidad intestinal, pueden favorecer una acidosis D-láctica. Presentamos un caso clínico de acidosis D-láctica recurrente en una niña de cinco años con síndrome de intestino corto secundario a un vólvulo de intestino medio. Recibió tratamiento antibiótico para el sobrecrecimiento bacteriano y restricción de carbohidratos enterales, pese a lo cual presentó recurrencias. Posteriormente, se sustituyó un 25% de su fórmula de nutrición enteral por otra con aporte exclusivo de fructosa, y se restringieron los aportes de otros azúcares fermentables. La evolución a los 16 años ha sido satisfactoria, sin presentar nuevas recurrencias

D-lactic acidosis is an infrequent complication, mainly reported in patients with short bowel syndrome. It is characterized by recurrent episodes of encephalopathy with elevated serum D-lactic acid, usually associating metabolic acidosis. The presence of D-lactate-producing bacteria is necessary for the development of this complication. Other factors, such as the ingestion of large amounts of carbohydrates or reduced intestinal motility, contribute to D-lactic acidosis. We report a case of recurrent D-lactic acidosis in a 5-year-old girl with short bowel syndrome, due to a midgut volvulus. She initially received oral antibiotics in order to treat bacterial overgrowth, together with oral carbohydrates restriction. Nevertheless, recurrences did occur. Subsequently, 25% of the enteral nutrition was replaced for a formula containing fructose exclusively, while other fermentable sugars were restricted from the diet. After 16 years of follow up, further recurrences of D-lactic acidosis were not observed

The incidence of infants with rotavirus enteritis combined with lactose intolerance.

UNLABELLED: This study was to research the incidence of infants with rotavirus enteritis combined with lactose intolerance and the clinical effect of low lactose milk powder for infantile rotavirus enteritis with lactose intolerance. The control groups were 126 cases of infants with diarrhea randomly collected from our hospital at the same period, which their rotavirus detection was negative. The observation group was 185 cases of infants with rotavirus, which was tested to be positive. Through the urine galactose determination, 62 cases of the control group were positive and 124 cases of the observation group were positive. Then 124 cases of infants with rotavirus combined with lactose intolerance were randomly divided into two groups. 60 cases in the control group were given rehydration, correction of acidosis, oral smecta, Intestinal probiotics and other conventional treatment, then continued to the original feeding method. While, 64 cases in the treatment group, on the basis of routine treatment, applied the low lactose milk feeding. To observe the total effective rate for the two groups. The incidence of lactose intolerance in children with rotavirus enteritis (67.03%) was significantly higher than that of children with diarrhea (49.2%), which was tested to be negative. And the difference was statistically significant (p<0.5). In the aspect of reducing the frequency of diarrhea, and diarrhea stool forming time, the treatment group has the obvious superiority. The total effective rate was 95.4% for treatment group, which was higher than that in the control group (76.7%), the difference was statistically significant (P<0.05). CONCLUSION: Infants with rotavirus enteritis was easier to merge with lactose intolerance. The low lactose milk powder could improve the therapeutic effectively and could reduce the duration of disease, and restored to normal diet for 2 weeks feeding time.

Bases para la terapia con líquidos y electrólitos. Modelos fisiológicos del equilibrio ácido-base (III): Uso práctico del modelo fisicoquímico de Stewart a pie de cama en la unidad de cuidados intensivos pediátrica (parte 2) / Basis for fluid and electrolyte therapy. Physiological models of acid-base balance (III): Practical use of Stewart’s physico-chemical model bedside in the pediatric intensive care unit (part 2)

En las últimas dos décadas hemos asistido a una revolución en el conocimiento científico de la fisiología y las alteraciones del equilibrio ácido-base. En la primera parte de esta serie de ar­tículos revisamos el modelo «tradicional», la aproximación centrada en el bicarbonato y basada en el trabajo pionero de Henderson y Hasselbalch, que es aún la más utilizada en la práctica clínica diaria. En la segunda y la tercera parte revisamos la teoría de otros modelos más modernos, particularmente el de Stewart, derivado al final de los años setenta desde las leyes de la química física. Con este modelo, tal como fue desarrollado por Peter Stewart y Peter Constable, utilizando la presión parcial de dióxido de carbono (pCO2), la diferencia de iones fuertes (SID) y la concentración total de ácidos débiles ([Atot]), somos capaces de predecir con exactitud la acidez del plasma y deducir el saldo neto de iones no medidos (NUI). La interpretación del equilibrio ácido-base no será nunca más un arte intuitivo y arcano. Se ha convertido en un cálculo exacto que puede realizarse automáticamente con ayuda del software moderno. En las últimas tres partes, utilizando a pie de cama el strong ion calculator y la historia clínica, mostraremos cómo el modelo fisicoquímico cuantitativo tiene ventajas sobre los tradicionales, principalmente en las situaciones fisiológicas extremas que se viven con los pacientes de la unidad de cuidados intensivos pediátrica o en las alteraciones congénitas del metabolismo (AU)

A revolution has recently undergone in the last two decades in the scientific understanding of acid-base physiology and dysfunction. In the first part of this series we review the "traditional" model, the current bicarbonate-centered approach based on the pioneering work of Henderson and Hasselbalch, still the most widely used in clinical practice. In the second and third part we review theoretically other modern approaches, particularly Stewart's one, derived in the late 1970s from the laws of physical chemistry. Whit this approach, as developed by Peter Stewart and Peter Constable, using the partial pressure of carbon dioxide (pCO2), the strong ion difference (SID) and the concentration of weak acids ([Atot]) we can now predict accurately the acidity of plasma and deduce the net concentration of unmeasured ions (NUI). Acid-base interpretation has ceased to be an intuitive an arcane art and became an exact computation that can be automated with modern software. In the last three parts, using at the bedside the quantitative strong ion calculator together with the medical history, we show how quantitative acid-base analysis has advantages over traditional approaches, mainly in the extreme physiological situations of clinical scenarios like the paediatric intensive care unit or the congenital metabolic diseases (AU)

Obesity and reversed growth retardation in a child with type Ia glycogen storage disease.

Type Ia Glycogen storage disease is an autosomal recessive hepatic metabolic disease due to a lack of glucose-6-phosphatase (G-6-Pase) activity presenting with growth retardation, lactic acidosis, fasting hypoglycemia with hypoinsulinemia, hyperuricemia, hepatomegaly, and hepatic adenoma with a risk of malignancy. The gene that encodes G-6-Pase was mapped to 17q21. There are some genotype-phenotype correlations. We report a case with delF327 mutation which is devoid of G-6-Pase activity; however clinical presentation in this case differs somewhat. Although correction of hypoglycemia and lactic acidosis with nocturnal intragastric feeding and uncooked starch therapy improves growth failure, mean height of the patients is often less than the target. Normal height and obesity in this case with hepatic steatosis and low hepatic glycogen storage requires clinical reevaluation since there are some overlapping phenotypes between type Ia GSD and metabolic syndrome. The phenomenon may be related to insulin resistance as a consequence of early aggressive nutrition therapy with frequent low glycemic index meals.

Use of base in the treatment of acute severe organic acidosis by nephrologists and critical care physicians: results of an online survey.

BACKGROUND: Acute severe metabolic acidosis associated with lactic acidosis or ketoacidosis can have severe detrimental effects on organ function, and might contribute to mortality. A general consensus exists that elimination of the cause of the acidosis is essential for treatment, but there is controversy concerning the use of base for the treatment of these disorders. Some physicians advocate administration of base when the acidosis is severe to prevent a decrease in cardiac output, whereas others oppose administration of base even when the acidosis is severe given the potential compromise of cardiac function. Nephrologists and critical care specialists are often the physicians developing recommendations for the treatment of severe acid-base disorders. METHODS: A short online survey of 20 questions was developed to assess the approach to the treatment of acute metabolic acidosis of program directors of fellowship programs and experts from the specialties of critical care and nephrology. RESULTS: Although there was variability among individual physicians from both specialties, a larger percentage of nephrologists than critical care physicians queried recommended administration of base for the treatment of lactic acidosis (86% vs 67%) and ketoacidosis (60% vs 28%). Also, critical care physicians in general used a lower level of blood pH when deciding when to initiate treatment. Of the physicians who gave base, most utilized sodium bicarbonate as the form of base given. CONCLUSIONS: The results of this survey indicate that the decisions whether to use base for the treatment of acute severe metabolic acidosis, and under which circumstances, vary among physicians, and indicate the need for further studies to develop evidence-based guidelines for therapy.

Colonic lactate metabolism and D-lactic acidosis.

D-Lactic acidosis is seen in patients with intestinal bypass or short bowels in whom colonic produced D-lactate accumulates. An intestinal bypassed patient with D-lactic acidosis had higher fecal D-lactate (122.4 mmol/liter) and L-lactate (90.1 mmol/liter) than described before in humans. D-Lactate fluctuated between 0.5 and 3.1 mmol/liter in plasma (normal < 0.1 mmol/liter) and between 1.1 and 52.8 mmol/liter in urine (normal < 0.7 mmol/liter) within a few hours, indicating that the human organism do metabolize and excrete D-lactate. The patient with D-lactic acidosis had a 10-fold increased DL-lactate production from glucose in fecal homogenates compared to 14 healthy controls and a patient with intestinal bypass, who did not have D-lactic acidosis. A 67% carbohydrate (starch)-enriched diet resulted in a minor elevation of fecal and plasma lactate, whereas 50 + 100 + 150 g of ingested lactose increased D-lactate in feces (84.0 mmol/liter) and plasma (2.3 mmol/liter) considerably in the patient with D-lactic acidosis. Intestinal prolongation (22 cm ileum) had a temporary effect on fecal and plasma D-lactate, but intestinal continuity was reestablished 26 months later because D-lactic acidosis recurred (plasma 8.6 mmol/liter, urine 101.3 mmol/liter). Large amounts of lactulose (160 g/day) to 12 normal individuals increased D-lactate to 13.6 +/- 3.5 mmol/liter in feces, but never increased D-lactate in plasma or urine. The in vitro fermentation of glucose in fecal homogenates increased DL-lactate, which disappeared after complete metabolization of the glucose. L-Lactate was converted to D-lactate and vice versa, and both were degraded to the short-chain fatty acids acetate, propionate, and butyrate. An infrequent, but elevated ability of the colonic flora to produce lactate may be a prerequisite for D-lactic acidosis to occur and may explain why the syndrome is so seldom seen even in patients with intestinal bypass or short bowels. The suggestion that D-lactate is not metabolized and hence accumulates is probably not valid.

[Recurrent D-lactic acidosis with encephalopathy in a boy with short-bowel syndrome]. / Rezidivierende D-Lactat-Acidosen mit Enzephalopathie bei einem Jungen mit Kurzdarmsyndrom.

For two years after surgical small-intestine duplication a 9-year-old boy with the short bowel syndrome had recurrent acidosis which caused severe failure to thrive. During the acidotic crises he had behavioural disorders, unsteady gait, indistinct speech, lid raising weakness with vision paresis and occasional somnolence. These signs disappeared after the aciduria had been treated with high doses of bicarbonate. D-lactic acidosis was finally diagnosed by simultaneously determining D-lactate (8.9 mmol/l [normal < 0.5]) and L-lactate (1.4 mmol/l [normal < 1.78]) during an episode of aciduria (pH 7.3, base excess -11.8 mmol/l). Further acidotic crises were prevented by a carbohydrate-modified diet, on which he gained 8 kg in one year.

Dietary management of D-lactic acidosis in short bowel syndrome.

Manipulation of carbohydrate intake was used to treat severe, recurrent D-lactic acidosis in a patient with short bowel syndrome. Dietary carbohydrate composition was determined after assessment of D-lactic acid production from various carbohydrate substrates by faecal flora in vitro. This approach may be preferable to repeated courses of antibiotics.