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Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e3181c48cde
Case Reports

D-Lactic Acidosis: “Right-Left Disorientation” in Laboratory Testing: Acute Encephalopathy in a Child With Carbohydrate Malabsorption Syndrome

Grünert, Sarah; Schmidts, Miriam; Kenzel, Sybille; Sass, Jörn Oliver; Greiner, Peter; Pohl, Martin; Hentschel, Roland

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From the Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany.

Received 23 April, 2009

Accepted 29 September, 2009

Address correspondence and reprint requests to Dr Sarah Grünert, Zentrum für Kinder- und Jugendmedizin, Mathildenstrasse 1, 79106 Freiburg, Germany (e-mail: sarah.gruenert@uniklinik-freiburg.de).

The authors report no conflicts of interest.

D-Lactic acidosis can occur as a rare and severe complication in patients with short bowel syndrome. In healthy individuals, relatively small amounts of glucose and starch reach the colon because of extensive absorption in the small intestine. In patients with short bowel syndrome, delivery of these substrates to the colon is significantly increased. Due to an overgrowth of Gram-positive anaerobic rods, such as Lactobacillus, glucose and starch are metabolized in the colon to D-lactic acid, which is then absorbed into the systemic circulation leading to metabolic acidosis. Because D-lactate is neurotoxic (1), the clinical presentation is characterized by episodes of encephalopathy with neurological symptoms such as altered mental status, confusion, slurred speech, ataxia, hallucinations, and amnesia (2,3). D-Lactic acid is not detected in routine laboratory tests using L-lactate dehydrogenase.

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CASE REPORT

The patient is a 7-year-old boy and the first child of consanguineous Turkish parents. Since the neonatal period, he has experienced chronic diarrhea and failure to thrive. Small bowel and gastric histology showed an eosinophilia of the mucosa and chronic gastritis. Enzymatic studies of intestinal mucosa revealed a deficiency of disaccharidases (lactase and sucrase). Genetic analysis of the SLC5A1 gene was performed to test for congenital glucose-galactose malabsorption, but no mutation could be found. Thus, the specific cause of the carbohydrate malabsorption remained unclear. Owing to the child's failure to thrive, a central venous catheter was implanted at the age of 4 weeks and additive parenteral nutrition was administered until the age of 7 years, when the catheter was removed because of acute staphylococcal sepsis. Six weeks later he underwent ambulant dental surgery due to a dental abscess, and 1 dose of clindamycin was administered orally. The next morning he was found comatose. On hospital admission, the Glasgow Coma Scale score was 8. Routine laboratory testing revealed extensive metabolic acidosis (pH 7.13, base excess −21.5 mmol/L, bicarbonate 7 mmol/L) with an increased anion gap despite normal serum lactate levels (L-lactate) and no ketonuria. Magnetic resonance imaging of the brain showed no pathological findings. After bicarbonate and glucose/electrolyte infusion he recovered quickly from neurological impairment and became alert again within a few hours. Within the next few days, 2 further episodes of acute encephalopathy with coma occurred after he consumed carbohydrate-rich meals. The third episode was not accompanied by metabolic acidosis. The gas chromatographic analysis of urine organic acids revealed high amounts of lactate in the urine of the patient. Mass-selective detection after chiral separation of methylated enantiomers (D and L) of lactate showed that the predominant compound was D-lactate (Fig. 1). Quantification of D-lactate in serum and urine by an enzymatic assay using D-lactate dehydrogenase yielded D-lactate levels of 14.2 and 83.9 mmol/L, respectively (normal: only traces).

Figure 1
Figure 1
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After oral administration of vancomycin and start of a low-carbohydrate diet, the patient's condition improved significantly. No further episode of encephalopathy occurred. D-Lactate levels in the serum and urine normalized.

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DISCUSSION

D-Lactic acidosis is described as a rare and severe complication in patients with short bowel syndrome, especially after jejunoileal bypass surgery or extensive small bowel resection. In children, the most frequent causes of surgical resection of the intestine are intestinal volvulus, necrotizing enterocolitis, arterial and venous thrombosis, and Crohn disease (4). Elevated D-lactate levels have also been described in patients with other gastrointestinal diseases such as ischemic colitis, unresectable adenocarcinoma of the colon, hemorrhagic pancreatitis with pseudocyst, colonic resection for adenocarcinoma, diverticulosis, and gastric obstruction due to lymphomatous infiltration (5). To our knowledge, this is the first case of symptomatic D-lactic acidosis in a child with functional short bowel syndrome due to carbohydrate malabsorption.

The carbohydrate malabsorption syndrome in our patient was already diagnosed during the neonatal period due to chronic diarrhea. The patient was treated with partial parenteral nutrition for many years, probably resulting in a rather low oral carbohydrate intake. This may have prevented symptoms of D-lactic acidosis until the age of 7 years. Stopping the additive parenteral nutrition may have led to increased carbohydrate intake, enhancing the formation of D-lactate from Gram-positive anaerobic rods in the colon. In many patients described in the literature, a delay of months to years occurred between the time of bowel surgery and the development of clinical signs of D-lactic acidosis (6,7).

In patients with short bowel syndrome who do not receive antibiotics, more than 60% of the fecal flora consists of Gram-positive rods, mainly lactobacilli (8). Oral antibiotics may induce D-lactic acidosis in patients with short bowel syndrome by promoting the overgrowth of antibiotic-resistant D-lactate–producing organisms (6,9) at the expense of other competing bowel flora (10). Although no overgrowth with Lactobacillus could be proven in our patient, oral administration of clindamycin for treatment of a dental abscess may have contributed to the development of the encephalopathic crisis.

Symptoms of D-lactate encephalopathy are sensitive but not necessarily specific for this disorder (5). Although symptoms are known to occur at high D-lactate levels, the clinical threshold may vary from patient to patient (5), and correlation between plasma D-lactate levels and severity of symptoms seems to be poor (3). Clinical reports of neurological dysfunction suggest that clinical signs are likely to be seen when D-lactate levels exceed 3 mmol/L (3,5). Our patient was deeply comatose with a D-lactate level of 14.2 mmol/L. Thurn et al (5) found that 16 of 33 patients with jejunoileal bypass reported neurological symptoms consistent with D-lactic encephalopathy, but only 9 had markedly elevated levels of D-lactate (greater than 0.5 mmol/L, range 0.7–11.5 mmol/L).

D-Lactic acidosis is usually self-limiting, and its duration, from hours to days, seems to depend on a balance among the rates of D-lactate production, absorption, utilization, and renal excretion (6).

Traditional treatment of this disease consists of altering the intestinal flora with antibiotics and minimizing the metabolic substrate by using a low-carbohydrate diet (11). In patients with refractory D-lactic acidosis, surgical intervention using serial transverse enteroplasty can be considered as a potential therapy (12).

The pathomechanism leading to the typical neurological manifestation is still not fully understood. Acidemia does not by itself account for the neurological symptoms because even more profound acidosis from other causes usually is not associated with these manifestations (6). Additionally, several patients have been reported with characteristic D-lactate encephalopathy but without severe systemic acidosis (5), as seen in our patient during the third episode of coma. As D-lactic acidosis also occurs in monogastrics and ruminants such as cattle, cats, and dogs (13–15), Abeysekara et al (1) studied the consequences of different infusions including D-lactic acid, L-lactic acid, and hydrochloric acid in calves. The objective of this experiment was to determine whether acidification of nervous tissue or D-lactic acid itself is responsible for impaired neurological function. D-Lactic acid infusion produced the greatest impairment of central nervous system function. Although hydrochloric acid infusion produced severe acidemia and cerebrospinal fluid acidosis, only minor effects on neurological function were evident, suggesting that D-lactate has a direct neurotoxic effect that is independent of acidosis. However, neither intravenous infusions nor oral administration of D-lactate in healthy humans has reproduced the neurological dysfunction, although serum levels up to 6 mmol/L in 1 study (16) and up to 3.5 mmol/L in another study (17) were attained. Coronado et al (6) suggest that patients with short bowel syndrome may develop symptoms at lower concentrations than healthy individuals, and certain nutritional deficiencies or unknown metabolites may predispose these patients to neurological dysfunction when they are exposed to D-lactate.

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CONCLUSIONS

Our case shows that D-lactate encephalopathy should be suspected and serum D-lactate measured whenever neurological symptoms occur in a patient with a condition involving the intestine, including “functional short bowel syndromes” such as carbohydrate malabsorption. As D-lactic acid is not detected by conventional laboratory techniques, special laboratory tests such as chromatographic analyses or D-lactate specific enzymatic tests must be performed when D-lactic acidosis is suspected.

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REFERENCES

1. Abeysekara S, Naylor JM, Wassef AW, et al. D-Lactic acid-induced neurotoxicity in a calf model. Am J Physiol Endocrinol Metab 2007; 293:E558–E565.

2. Petersen C. D-Lactic acidosis. Nutr Clin Pract 2005; 20:634–645.

3. Uribarri J, Oh MS, Carroll HJ. D-Lactic acidosis. A review of clinical presentation, biochemical features, and pathophysiologic mechanisms. Medicine (Baltimore) 1998; 77:73–82.

4. Soler Palacín P, Garzón Lorenzo P, Castilla Fernández Y, et al. D-Lactic acidosis in an 11-year-old patient with short bowel syndrome. An Pediatr 2006; 64:385–387.

5. Thurn JR, Pierpont GL, Ludvigsen CW, et al. D-Lactate encephalopathy. Am J Med 1985; 79:717–721.

6. Coronado BE, Opal SM, Yoburn DC. Antibiotic-induced D-lactic acidosis. Ann Intern Med 1995; 122:839–842.

7. Narula RK, El Shafei A, Ramaiah D, et al. D-Lactic acidosis 23 years after jejuno-ileal bypass. Am J Kidney Dis 2000; 36:E9.

8. Bongaerts G, Bakkeren J, Severijnen R, et al. Lactobacilli and acidosis in children with short small bowel. J Pediatr Gastroenterol Nutr 2000; 30:288–293.

9. Flourie B, Messing B, Bismuth E, et al. D-Lactic acidosis and encephalopathy in short-bowel syndrome occurring during antibiotic treatment. Gastroenterol Clin Biol 1990; 14:596–598.

10. Zhang DL, Jiang ZW, Jiang J, et al. D-Lactic acidosis secondary to short bowel syndrome. Postgrad Med J 2003; 79:110–112.

11. Mayne AJ, Handy DJ, Preece MA, et al. Dietary management of D-lactic acidosis in short bowel syndrome. Arch Dis Child 1990; 65:229–231.

12. Modi BP, Langer M, Duggan C, et al. Serial transverse enteroplasty for management of refractory D-lactic acidosis in short-bowel syndrome. J Pediatr Gastroenterol Nutr 2006; 43:395–397.

13. Packer RA, Cohn LA, Wohlstadter DR, et al. D-Lactic acidosis secondary to exocrine pancreatic insufficiency in a cat. J Vet Intern Med 2005; 19:106–110.

14. Stämpfli H. D-Lactate metabolism and the clinical signs of D-lactataemia in calves. Vet Rec 2005; 156:816.

15. Ewaschuk JB, Naylor JM, Zello GA. D-Lactate in human and ruminant metabolism. J Nutr 2005; 135:1619–1625.

16. Oh MS, Uribarri J, Alveranga D, et al. Metabolic utilization and renal handling of D-lactate in men. Metabolism 1985; 34:621–625.

17. De Vrese M, Koppenhoefer B, Barth CA. D-Lactic acid metabolism after an oral load of DL-lactate. Clin Nutr 1990; 9:23–28.

© 2010 Lippincott Williams & Wilkins, Inc.

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