Literature review on congenital glucose–galactose malabsorption from 2001 to 2019

Abstract

Aim: Congenital glucose-galactose malabsorption (CGGM) is a rare disease characterised by severe diarrhoea, dehydration and weight loss. To better understand CGGM, we investigated all the case reports and series of CGGM from 2001 to 2019. Methods: A review of reports of CGGM published from 2001 to 2019 was undertaken, using PubMed, Ovid Medline, Springer, Wanfang Database, CBMD database and CKNI database. The clinical features, diagnosis, treatment and prognosis of CGGM in these reports were obtained and analysed. Results: We reviewed 107 cases for this study. Out of 55 cases from Saudi Arabia and Turkey, 43 cases (78.2%) were from consanguineous marriage. Forty-nine cases (73.1%) were infants. Dehydration, diarrhoea and weight loss occurred in almost all cases. Half of the cases presented hypernatremia and abdominal distension. Vomiting, polyuria/haematuria and fever were reported in 11, 7 and 3 cases, respectively. Twenty cases (18.7%) showed hypercalcaemia or nephrolithiasis. Stool pH was tested in 43 cases (40.2%). Fifty-five cases (51.4%) were diagnosed for more than 1 month after the onset of symptoms. Two cases (1.9%) died, one needed amputation, and the other 104 cases (97.2%) recovered with fructose formula. Seventy-three cases (68.2%) underwent gene testing, 30 SLC5A1 gene mutations were detected, with 23 cases homozygous, and seven heterozygous mutation. Conclusion: The clinical characteristics of CGGM are nonspecific, and the diagnosis method is not conventionally applied. Fasting and gene testing are the two most important diagnostic methods. The best treatment of CGGM is supplementation with fructose-based formula.

Congenital Glucose-Galactose Malabsorption: A Case With a Novel SLC5A1 Mutation in a Saudi Infant

“…Data are lacking regarding the incidence or prevalence of this disease. A recent review by Wang et al reported that out of 107 reviewed cases, 55 cases were from Saudi Arabia and Turkey, accounting for 78.2% of the total number of published cases [ 3 ]. Physicians should be vigilant in those countries when an infant presents with intractable, profuse watery diarrhea and dehydration along with failure to thrive that persist regardless of standard therapy.…”

“…In healthy infants, the intestinal sodium-dependent glucose cotransporter (SGLT1) drives glucose and water against their concentration gradients into enterocytes via Na+ and electrical gradients [ 2 ]. Mutations in SLC5A1 gene lead to a defect in SGLT1 across the intestinal brush border, which results in accumulation of unabsorbed sodium, glucose, and galactose inside the intestinal lumen [ 3 ]. GGM is characterized by neonatal onset of severe watery diarrhea that is fatal within few weeks without proper management [ 2 ].…”

“…Infants diagnosed with GGM prenatally may thrive on fructose-based formula and subsequently will continue on a fructose-based solid diet [ 1 ]. Epidemiological data for GGM are lacking, with only 107 documented cases from 2001 to 2019 worldwide [ 3 ], and it is challenging for clinicians to consider GGM as an initial diagnosis. Here we present the clinical and diagnostic course of a Saudi infant with GGM found to have a heterozygous mutation in SLC5A1 gene.…”

NGS Gene Panel Analysis Revealed Novel Mutations in Patients with Rare Congenital Diarrheal Disorders

“…CTE is due to villous atrophy with crypt hyperplasia and focal crowding of surface enterocytes that resemble tufts, evidenced by histology of intestinal samples, total or partial villus atrophy, and crypt hyperplasia in the absence of inflammation, with the typical focal epithelial tufts that permit the differential diagnosis between MVID and CTE [15]. The diagnosis of GGM is based on a combination of tests that includes stool sugar analysis, hydrogen exhalation, and small bowel histology [26]. In patients with CCDs, molecular analysis may help define the therapeutic strategy.…”

Genetic causes of neonatal and infantile hypercalcaemia

“…The majority of mutations in SGLT-1 are nonsense, frameshift or splice site, resulting in truncated proteins that are not expressed [ 79 ]. Missense mutations have been reported, which do not affect protein expression, but impair the transport ability of the protein [ 79 , 80 ]. Hypercalcaemia occurs in ~20% of cases and can be accompanied by nephrocalcinosis and elevated 1,25(OH) 2 D 3 [ 80 ].…”