The Invitae Rare Carbohydrate Disorders Panel analyzes the FBP1 and SLC5A1 genes. Pathogenic variants in FBP1 lead to a rare carbohydrate disorder fructose-1,6 bisphosphatase deficiency. Pathogenic variants in SLC5A1 lead to glucose-galactose malabsorption (GGM).
This panel is useful for the diagnosis of patients whose clinical symptoms or biochemical findings indicate rare carbohydrate disorders. Newborns and infants may present with life threatening symptoms. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of disease-causing variants provides accurate risk assessment and carrier status of at-risk relatives.
Individuals affected with fructose-1,6-bisphosphatase (FBPase) deficiency typically experience a first episode of metabolic decompensation before the age of two years. Metabolic crises are triggered by fever, decreased food intake, or consumption of fructose containing food and are characterized by hypoglycemia and lactic acidosis. Metabolic crises may also cause hepatomegaly, acidoketosis, hyperventilation, dyspnea, irritability, tachycardia, somnolence, hypotonia, coma, seizures, and brain damage.
Infants affected with Glucose-galactose malabsorption (GGM) experience severe neonatal diarrhea and dehydration due to a defect in glucose and galactose transport across the intestinal brush border. Symptoms include glycosuria, weight loss, increased bowel sounds, distended abdomen and irritability or lethargy. If treated with carbohydrate-free formula, individuals recover quickly and have normal growth and development. Tolerance to carbohydrate-containing diet improves gradually over time and most individuals are able to tolerate regular carbohydrate-containing diets by their twenties.
FPB1 is the only gene known to be associated with fructose-1,6 bisphosphatase deficiency. However, due to the rarity of this condition, the percent of fructose-1,6 bisphosphatase deficiency attributed to pathogenic variants in FPB1 is currently unknown.
SLC5A1 is the only gene known to be associated with glucose-galactose malabsorption. However, due to the rarity of this condition, the percent of glucose-galactose malabsorption attributed to pathogenic variants in SLC5A1 is currently unknown.
FBPase deficiency and GGM are inherited in an autosomal recessive manner.
The prevalence of FBPase deficiency is estimated to be approximately 1 in 350,000 to 900,000 live births based on studies in Germany and France, respectively. The exact prevalence of GGM is unknown, but is thought be rare.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|