Molecular Diagnosis of Congenital Sucrase-isomaltase Deficiency (CSID)
SI Gene Sequence Analysis
Background:
Congenital Sucrase Isomaltase Deficiency (CSID) is an intestinal mal-absorption syndrome with reduced capacity to digest sugars and complex carbohydrates, resulting in chronic diarrhea, abdominal bloating/pain, and failure to thrive. The symptoms are highly variable. Infants can be severe with chronic explosive diarrhea, distended abdomens and failure to thrive. Some teens and adults may have “chronic non-specific diarrhea,” and others may be misdiagnosed with “irritable bowel syndrome.” CSID is caused by mutations in the SI gene, located on chromosome 3. The gene is about 100 kb in length and has 48 exons coding for two enzymes, sucrase and isomaltase. CSID is a pan-ethnic disease inherited in an autosomal recessive pattern. There exist four common mutations in the North American population; p.G1073D, p.V577G, p.F1745C and p.R1124X, with frequencies of 31%, 15%, 7% and 6% respectively. At least 83% will have at least one of these 4 common mutations, with 35% being homozygous and 48% being heterozygous. There is some evidence that heterozygotes can be symptomatic as well. For patients suspected of CSID, molecular testing may be a less expensive and less invasive approach to diagnostic testing than bowel biopsy and enzyme analysis.
Indications for Testing:
Symptomatic for CSID.
Symptomatic individual with Family member with known mutation.
Testing Methods:
For sequencing the entire SI gene: Amplification of SI gene coding region is performed by PCR on patient genomic DNA. Bi-directional DNA sequence analysis is performed on PCR products using automated Fluorescent dideoxy sequencing methods.
For sequencing the 4 common mutation panel: the SI genomic regions harboring the target mutations are amplified by PCR. DNA sequence analysis is performed on PCR products using automated, fluorescent dideoxy sequencing methods.
Specimen Requirements:
Blood: EDTA (purple-top) tubes: Adult/Child: 5-6 cc; Infant: 2-3 cc.
or Filter paper blood spot card.
or DNA: If the DNA quality is good (A260/A280 ratio between 1.8 and 1.9), we request at least 1 microgram of DNA regardless how much volume it is. Additionally, dilution should be >50 ng/ul.
Requisition form is required for each specimen. Please contact the laboratory for more detailed information.
Turnaround Time:
4 weeks
CPT codes and prices:
| Sample | CPT codes | Prices |
| Index case | 81479 (formerly 83891, 83898x48, 83904x48, 83909, 83912) | $7,383 |
| Index case - panel for 4 common mutations | 81479 (formerly 83891, 83898x4, 83904x4, 83909, 83912) | $967 |
| Circumpolar 5-mutation panel (the four common mutations plus c.273_274delAG) | 81479 (formerly 83891, 83898x4, 83904x4, 83909, 83912) | $1,111 |
| Family member for known mutation | 81479 (formerly 3891, 83898x2, 83904x2, 83909, 83912) | $681 |
References:
Marcadier JL, et al. 2015 Can Med Assoc J 187:102-7
Uhrich S, et al, 2012, J Pediatr Gastroenterol Nutr 55:(Suppl 2): S34-S35.
Treem WR, 1996, Pediat 128: 727-729.
Spodsberg N, et al, 2001, J Biol Chem 276: 23506-23510.
Sander P, et al, 2006, Hum Mutat 27: 119 only.
Ritz V, et al, 2003, Gastroenterology 125: 1678-1685.
Ouwendijk J, et al, 1996, Clin Invest 97: 633-641.