Pakistan Journal of Medical Sciences

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CASE REPORT

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Volume 23

October - December 2007 (Part-II)

Number  6


 

Abstract
PDF of this Article

Glucose-galactose malabsorbtion syndrome
presenting as congenital diarrhea

Mandana Rafeey1, Ali Golzar2

ABSTRACT

We describe the clinical history, diagnostic evaluation, and management of an infant who had congenital Glucose Galactose Malabsorption (GGM), a rare disorder thought to be inherited as an autosomol recessive trait. This infant experienced persistant diarrhea and hypernatemic dehydration during the first months of life and then renal stone on three months follow-up. Diagnosis is based on oral glucose tolerance test, stool reducing substances and rule out other diseases with use of laboratory investigations, small-bowel biopsy, and histology. Parentral education about dietary managemented with fructose based formula and solid food feedings was important component of this patients treatment.

KEYWORDS: Glucose galactose, Malabsorption, Chronic diarrhea, Child.

Pak J Med Sci    October - December 2007 (Part-II)    Vol. 23 No. 6    959-961


1. Mandana Rafeey,
Associate Professor of Pediatric Gastroenterology,
Liver and Gastrointestinal Disease Research Center,
2. Ali Golzar,
Resident of Pediatrics,
1-2: Tabriz University of Medical Sciences,
Tabriz – Iran.

Correspondence

Dr. Mandana Rafeey,
Associated Professor,
Liver and Gastrointestinal Disease Research Center,
Tabriz University of Medical Sciences,
Tabriz – Iran. Add: Children Hospital,
Sheshglan Street, P.O. BOx: 57367
Tabriz, Iran.
Email: mrafeey@yahoo.com 

* Received for publication: February 7, 2007
* Revision Received: September 1, 2007
* Final Revision Accepted: September 22, 2007


INTRODUCTION

Transport of water-soluble molecules across tissue barriers has attracted increasing interest since 1952, suggesting that the transport across the erythrocyte membrane required a carrier mechanism to facilitate diffusion.1 Now it is established that transport and uptake of glucose can be rate-limiting in cells subject to large metabolic demands, as manifested by several disease states involving transport loss of function.2-3

Three types of concentrative Naþ/glucose transporters have been identified: SGLT1 (locus 22q13.1) is responsible for glucose absorption from the intestinal tract. SGLT2 (locus 16p11.2), together with SGLT1, is responsible for glucose absorption in the renal tubules. SGLT3 (locus 22q12.2-q12.3) is localized to the plasma membrane of enteric neurons and skeletal muscle, and is incapable of functioning as a homo-oligomer.4 Congenital glucose-galactose malabsorption (GGM), which is caused by defects of SGLT1, is an autosomal recessive disease characterized by the selective malabsorption of glucose and galactose.5,6 Patients with GGM present with neonatal onset of severe, watery and acidic diarrhea while taking glucose-containing or galactose-containing diets. The condition is life-threatening if not diagnosed and treated. Only approximately 200 individuals worldwide are currently known to be affected by GGM.6,7

All studied patients carry mutations in their SGLT1 genes, while parents are Non manifesting carriers, speaking to the autosomal recessive pattern of inheritance of this disease. Many patients are the product of consanguineous parents, emphasizing this concept. Diarrhea in GGM is osmotic, being caused by accumulation of unabsorbed glucose and galactose in the intestine.2 which stems from a defect in the active, transport mechanism of the two monosaccharide.8,9 This condition leads to failure to thrive and severe malnutrition.

In this report, we describe a patient from Iran, who’s clinical and laboratory findings confirmed diagnosis of GGM.

CASE REPORT

A 2-months-old Iranian boy born to first- degree consanguineous parents was referred with a history of watery, acidic diarrhea noted on the third day of his life. His antenatal and natal histories were normal condition. He had been re-hydrated with intravenous fluids and had been taken off breast feeding at a local hospital when he was seven days old. The diarrhea resolved after withdrawal of breast feeding but re-started when breast feeding was resumed. He had three admissions in local hospital for dehydration and acidosis. When he was two months old, be was admitted in our hospital with apathy and severe dehydration. Laboratory findings were: Hb 8.1g/dL, WBC 8000/mm3, platelets 408,000/mm3, serum Na190 mEq/L, serum K 3.2mEq/L, blood urea nitrogen 86mg/dL, serum creatinin 1.5mg/dL, arterial pH 7.1, serum HCO3 7.5mmol/L, urine specific gravity1025 with glucosuria (++). The stool pH was 5 and the stool was positive for reducing substances. At chromatography, the reducing substances were confirmed as glucose and galactose.

The blood glucose and galactose levels were measured by glucose oxidase reagent. Other data collected and tests included urine osmolality, analysis and urine electrolytes, renal ultrasound, and clinical response to special formula. Small-bowel biopsies were obtained from the duodenojejunal junction. Two biopsies were obtained and sent for histology. The child had hypernatremia, with a mean serum sodium level of 165mEq/L in the second time after hydration (range 160-190). All the investigations like serum calcium, phosphate, alkaline phosphatase, potassium, magnesium, chloride, blood urea nitrogen, immunoglobulin, albumin, sweat chloride, urine electrolytes, complete blood count, prothrombin time, and partial thromboplastin time were normal. Stools were positive for reducing substances, which were confirmed by sugar chromatography to be glucose and galactose; but negative for rotavirus and cryptosporidiosis. Stool culture showed no pathogens, and stool electrolytes were normal. Small-bowel aspiration for giardia was negative, and the culture showed no growth. Histology of the small-bowel biopsies was normal. Urine analysis showed glucosuria in our patient. The hypernatremic dehydration was treated with intravenous fluids and, after discontinuing enteral feeding, his diarrhea stopped. Diarrhea reoccurred after introducing lactose, dextrinmaltose or glucose-containing formulas. There was no diarrhea after starting a fructose-supplemented, carbohydrate-free formula. Child responded clinically to fructose-based formula, and he is thriving at follow-up. He grew normally and was discharged from the hospital at 3.5 months of age. Three months later, there was renal stones in his renal ultra sound. Based on clinical course and laboratory findings his diagnosis was GGM.

DISCUSSION

To the best of our knowledge, this is the first reported case of GGM from Iran. More than 40 mutations of SGLT1 responsible for GGM have been identified so far and fewer than 300 patients have been identified worldwide. This is inherited as an autosomal recessive trait.10,11 The family histories were positive for consanguinity and infantile death from chronic diarrhea in 50% of this case. The disease commonly affects girls, a finding that we didn’t observe in our study.3 The cause of female predominance in this disorder is unknown, but it might be related to genetic susceptibility. The high rate of consanguinity in our population and the occurrence of symptoms stemming from compound heterozygous mutations in autosomal recessive diseases suggest that the prevalence of genetically related disease may be higher in this area.

The initial symptom of GGM is watery diarrhea after initiation of milk feeding within a few days after birth, but other gastrointestinal symptoms are rare. The major clinical effect of chronic diarrhea on our child was failure to thrive, a finding that is in agreement with the literature.12

GGM might be associated with renal glycosuria due to renal tubular reabsorption defect, this condition was noted in our patient.13 Another association with GGM is renal stones, which was reported by Meeuwisse in 1969.14 The cause of renal stones in GGM is unknown.14,15 An interesting finding in GGM is hypernatremia from recurrent dehydration, which was noted in our patients.14,16 However, GGM may stem from acute gastroenteritis caused by rotavirus, which was not noted in our patient.3 Infants with GGM have impaired glucose and galactose absorption and normal fructose absorption.17 Treatment with lactose free milk,partial hydrolysate, and amino-acid formulas was not effective and continued watery diarrhea. However, it is important to exclude congenital disacchardiase deficiency (especially lactase), which appears as watery diarrhea from birth and low lactase levels.18,19 Diagnosis of GGM may also be made by measuring sugar and amino acid evoked potential differences in the jejunum in vivo, this last investigation was not made in our patient.20 Children with GGM usually respond dramatically to fructose-based formula with improvement in their diarrhea and growth, as seen in our patient.2

In summary, GGM is an important cause of chronic diarrhea in infants, particularly if it starts within a few days of milk feeding. Hence, treating physicians need to be vigilant in looking for this treatable cause of chronic diarrhea and to study the genetic basis of the disease in the Iranian children.

REFERENCES

1. Wright EM, Loo DD, Panayotova-Heiermann M, Hirayama BA, Turk E, Eskandari S, et al. Structure and function of the Na+/glucose cotransporter. Acta Physiol Scand 1998;643:257-64.

2. Gracey M, Bwike V. Sugar induced diarrhoea in children. Arch Dis Child 1973;48:331-6.

3. Evans L, Grasset E, Heyman M, Dumontier AM. Congenital selective malabsorption of glucose and galactose. J Pediatr Gastroenterol Nutr 1985;4(6):878-86.

4. Lindquist B, Meeuwisse GW. Chronic diarrhoea caused by monosaccharide malabsorption. Acta Paediatr Scand 1963;51:674-85.

5. Diez-Sampedro A, Hirayama BA, Osswald C, Gorboulev V, Baumgarten K, Volk C, et al. A glucose sensor hiding in a family of transporters. PNAS 2003;100:11753-8.

6. Mueckler M, Caruso C, Baldwin SA, Panico M, Blench I, Morris HR, et al. Sequence and structure of a human glucose transporter. Science 1985;6,229:941-5.

7. Wright EM, Martin MG, Turk E. Familial glucose-galactose malabsorption and hereditary renal glycosuria. In: Scriver CR, Baudet AL, Sly W, et al. eds. The Metabolic and Molecular Bases of Inherited Disease, 8th ed. New York: McGraw-Hill; 2001;4891-908.

8. Abraham JM, Levin B, Oberholzer VG, Russel A. Glucose-galactose malabsorption. Arch Dis Child 1967;42:592-7.

9. Booth IW, Patel PB, Sule D, Brown GA, Buick R, Beyreiss K. Glucose-galactose malabsorption: demonstration of specific jejunal brush borders membrane defect. Gut 1988;29:1661-5.

10. Joost HG, Bell GI, Best JD, Birnbaum MJ, Charron MJ, Chen YT, et al. Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators. Amer J Physiology, Endocrinology and Metabolism 2002;282:E974-6.

11. Desjeux J. The molecular and genetic basis of congenital transport of congenital defects. Gut 2000;46:585-7.

12. Marcovitch H. Failure to thrive. BMJ 1994;308:35-8.

13. Brodehl J, Oemar BS, Hoyer PF. Renal glycosuria. Pediatr Nephrol 1987;1:502-8.

14. Meeuwisse GW, Melin K. Glucose-galactose malabsorption: A clinical study of 6 cases. Acta Paediatr Scand 1969;(supp 188):3-18.

15. EL-Naggar W, Balfe JW, Barbar M, Taha D. Nephrocalcinosis in glucose-galactose malabsorption association with renal tubular acidosis. Pediatr Nephrol 2005;20(9):13336-9

16. Steinherz R, Nitzan M, Iancu TC. Hypernatremic dehydration as a sign leading to the diagnosis of glucose-galactose malabsorption in breast-fed neonates. Helv Paediatr Acta 1984;39:275-7.

17. Beyreiss K, Hoepffner W, Scheerschmidt G, Muller F. Digestion and absorption rates of lactose, glucose, galactose and fructose in three infants with congenital glucose-galactose malabsorption: perfusion studies. J Pediatr Gastroenterol Nutr 1985;4:887-92.

18. Dahlqvist A, Semenza G. Disaccharidases of small-intestinal mucosa. J Pediatr Gastroenterol Nutr 1985;4:857-67.

19. Wittenberg DF. Clinical aspects of lactose and lactase: Review of the literature. Pediatr Rev Common 1992;6:129-44.

20. Igarashi V, Ohkohchi N, Kikuta A, Suzuki J, Tada K. Diagnosis of congenital glucose-galactose malabsorption by measuring sugar and amino acid evoked potential differences in jejunum in vivo. J Pediatr Gastroenterol Nutr 1986;5:899-901.


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