February 07, 2018
Years published: 1988, 1989, 1993, 1994, 1995, 1998, 2005
Congenital sucrase-isomaltase deficiency (CSID) is a rare inherited metabolic disorder characterized by the deficiency or absence of the enzymes sucrase and isomaltase. This enzyme complex (sucrase-isomaltase) assists in the breakdown of a certain sugars (i.e., sucrose) and certain products of starch digestion (dextrins). The sucrase-isomaltase enzyme complex is normally found within the tiny, finger-like projections (microvilli or brush border) lining the small intestine. When this enzyme complex is deficient, nutrients based on ingested sucrose and starch cannot be absorbed properly from the gut.
Symptoms of this disorder become evident soon after sucrose or starches, as found in modified milk formulas with sucrose or polycose, are ingested by an affected infant. Breast-fed infants or those on lactose-only formula manifest no symptoms until such time as sucrose (found in fruit juices, solid foods, and/or some medications) is introduced into the diet. Symptoms are variable among affected individuals but usually include watery diarrhea, abdominal swelling (distension) and/or discomfort, among others. Intolerance to starch often disappears within the first few years of life and the symptoms of sucrose intolerance usually improve as the affected child ages. CSID is inherited as an autosomal recessive genetic trait.
CSID is a rare inherited metabolic disorder characterized by the deficiency or absence of the enzymes sucrase and isomaltase. When the concentration of this enzyme complex is low or absent, the breakdown of the disaccharide sucrose and starch and the subsequent absorption of smaller molecular components cannot take place.
Affected infants develop symptoms soon after they first ingest sucrose, as found in modified milk formulas, fruits, or starches. Symptoms may include explosive, watery diarrhea resulting in abnormally low levels of body fluids (dehydration), abdominal swelling (distension), and/or abdominal discomfort. In addition, some affected infants may experience malnutrition, resulting from malabsorption of essential nutrients, and/or a delay in growth and weight gain (failure to thrive), resulting from nutritional deficiencies. In some cases, individuals may exhibit irritability; colic; abrasion and/or irritation (excoriation) of the skin on the buttocks as a result of prolonged diarrhea episodes; and/or vomiting. Symptoms of this disorder vary among affected individuals. Symptoms are usually more severe in infants and young children than in adults.
Symptoms of CSID may be absent in an affected infant who is breast-fed or who is on a lactose-only formula; however, as soon as sucrose is introduced into the diet through fruit juices, solid food, medications, and/or other sources, symptoms may rapidly develop. Intolerance to starch may disappear within the first few months or years of life while sucrose intolerance, responsible for most of the symptoms of this disorder, often improves as the affected child ages, exhibiting only occasional or mild symptoms in adulthood. In some cases, symptoms may not be manifested until the onset of puberty.
Symptoms exhibited in infants and young children are usually more pronounced than those of the affected adults because the diet of younger individuals often includes a higher carbohydrate intake. In addition, the time it takes for intestinal digestion is less in infants or young children.
In some cases, the development of kidney stones (renal calculi) may be associated with CSID.
CSID is inherited as an autosomal recessive genetic trait. The faulty gene has been tracked to chromosome 3 (3q25-q26).
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 3q25-q26” refers to a region between band 25 and band 26 on the long arm of chromosome 3. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
Parents of some children with CSID may exhibit some defects in sucrase-isomaltase absorption, but do not display symptoms of this disorder. These parents are said to be heterozygous for the defective sucrase-isomaltase gene. Heterozygous is the term used to describe a person who has two different genes for a particular trait, one inherited form each parent. A person heterozygous for a genetic disease caused by a dominant gene will be affected with the disease. An individual heterozygous for a genetic disorder produced by a recessive gene will not usually be affected by the disease, or will have a milder form of it.
In addition, researchers have reported in the medical literature that parents of some individuals affected with CSID have been closely related by blood (consanguineous). If both parents carry the same disease gene, there is a higher than normal risk that their children may inherit the two genes necessary for the development of the disease.
CSID is a metabolic disorder that affects males and females in equal numbers and is diagnosed in approximately 0.2 percent of North Americans. This disorder has a higher frequency among Greenland and Canadian Inuit populations, with a reported incidence of approximately 10 percent. In addition, researchers report a higher degree of homozygosity among these more frequently affected groups than among other groups. Also, as a diagnosis may be easily missed, especially in those individuals with mild symptoms, many researchers suspect there may be a higher incidence of this disorder than is actually reported in the medical literature.
CSID may be suspected in any newborn infant exhibiting severe watery diarrhea after ingestion of milk-modified or glucose-polymer formula. The diagnosis of this disorder may be confirmed through clinical evaluation, characteristic findings, detailed patient history, and/or specialized testing. For example, after deliberate feeding of measured doses of sucrose, isomaltose, or its substitute, palatinose, for tolerance testing purposes, blood serum tests of an affected individual may reveal a flat serum glucose curve. In addition, blood and urine samples may reveal the presence of the disaccharide sucrose, isomaltose, or palatinose if used as a substitute during tolerance testing. The feces may exhibit sucrose, the monosaccharides glucose and fructose, and an acid ph level of below 5.0 or 6.0.
Diagnostic procedures may also include enzyme tests (assays) that measure the activity of sucrase-isomaltase in the intestine. This procedure usually involves the removal of a small sample of tissue (biopsy) from a certain area or areas of the small intestine. Other tests may include a sucrose hydrogen breath test in which an abnormally high level of hydrogen will be detected in the breath of an affected individual after sucrose ingestion.
Treatment of CSID focuses on dietary management through a low-sucrose or sucrose-free diet. In addition, a low-starch or starch-free diet is advised in some cases, especially in the first few years of life. Some affected individuals may show signs of sucrose tolerance during the second decade of life, but many others may exhibit a life-long sucrose intolerance. Individuals affected with this disorder may benefit from ingesting fresh baker’s yeast, which exhibits sucrase activity, after sucrose ingestion. Researchers suggest that the yeast be taken on a full stomach as sucrase activity is much more effective when the gastric juices are diluted.
The orphan drug sacrosidase oral solution (Sucraid) has been approved by the FDA for the treatment of congenital sucrose isomaltose malabsorption. This oral solution is an enzyme replacement therapy that contains the enzyme sucrase (sacrosidase), obtained from baker’s yeast and glycerin. Sucraid has been found to relieve many of the symptoms associated with sucrose ingestion by individuals with this disorder. Sacrosidase oral solution is manufactured by QOL Medical, LLC.
Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. For example, fluid and electrolyte replacement after episodes of diarrhea may be indicated to stave off dehydration and/or other associated symptoms.
A team approach for infants with this disorder may be of benefit and may include pediatricians, physicians who diagnose and treat disorders of the digestive tract (gastroenterologists), specialists who will assess and plan a diet that best achieves proper growth and development (nutritionists), special social support, and other medical services.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov
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For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Nichols BL, Avery SE, Karnskul W, et al. Congenital maltase-glucoamylase deficiency associate with lactase and sucrase deficiencies. J Pediatr Gastroenterol Nutr. 2002;35:573-79.
Belmont JW, Reid B, Taylor W, et al. Congenital sucrase-isomaltase deficiency presenting with failure to thrive, hypercalcemia, and nephrocalcinosis. BMC Pediatr. 2002;2:4.
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Disaccharide Intolerance I. Entry Number; 222900: Last Edit Date; 3/17/2004.
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