Infantile hypercalcemia is an uncommon presentation, even for a pediatric endocrinologist. However, the combination of diarrhea and hypercalcemia makes the situation particularly intriguing. In this report, the authors present the case of an infant referred to them for hypercalcemia, who had been experiencing watery diarrhea, abdominal distension, and failure to thrive since early neonatal age. The eventual diagnosis was congenital lactase deficiency. Targeted management with lactose-free feeds normalized calcium levels within a week of starting the therapy. During the first follow-up visit, three weeks after discharge, she exhibited a normal metabolic profile with optimum catch-up growth.

A 3-month-old girl presented with symptoms indicative of dysuria, gross hematuria, chronic diarrhea, and nephrocalcinosis. She was born to fourth-degree consanguineous parents. The infant exhibited hypercalciuria and hyperoxaluria, and her stool tested positive for reducing sugars. She responded positively to dietary lactose restriction, and her hyperoxaluria improved over the course of 3 months. This suggests an enteric hyperoxaluria phenotype, although her hypercalciuria persisted. Whole exome sequencing identified a homozygous variant in the LCT gene, which is associated with congenital lactase deficiency, as well as a heterozygous variant in the ADCY10 gene, which is linked to absorptive hypercalciuria.

There are currently three known congenital disaccharidase deficiencies: congenital lactase deficiency (CLD), congenital sucrase-isomaltase deficiency (CSD), and congenital trehalase deficiency (CTD). No congenital deficiency has been described for maltase-glucoamylase (MGAM). A literature search was performed in PubMed for the pathogenic variants CLD, CSD, and CTD and the articles retrieved were analyzed to estimate the prevalence of congenital disaccharidase deficiencies. Based on reported variants, the estimated prevalence was 1.3 per 106 births (95% CI: 1.1-1.7) for CLD, and 31.4 per 106 births (95% CI: 28.3-34.8) for CSD. Using data on previously reported variants and variants predicted to be loss-of-function in gnomAD, the overall estimated prevalence was 2.3 per 106 births (95% CI: 1.9-2.9) for CLD, 57.6 per 106 births (95% CI:52.5-63.2) for CSD, and 9.2 per 106 births (95% CI: 2.5-3.7) for CTD. The prevalence of CSD was found to be relatively high, while for other congenital disaccharidase deficiencies, the estimated prevalence was very low.

Patients with the rare autosomal recessive disorder congenital lactase deficiency (CLD) present with severe, potentially life-threatening symptoms shortly after birth. Several variants have been characterized within the gene for lactase-phlorizin hydrolase (LCT) that are associated with CLD. Here, we analyze at the biochemical and cellular levels LCT mutants harboring the genetic variants p.Y1390*, p.E1612*, p.S1150Pfs*19, p.S1121L, p.R1587H, and p.S688P. Our data unequivocally demonstrate that these mutants are absolutely transport incompetent, some of which are readily degraded, and are enzymatically inactive. The current study contributes to and expands our understanding on the pathogenesis of CLD at the molecular level.

Lactose is a reducing sugar consisting of galactose and glucose, linked by a β (1→4) glycosidic bond, considered as an antioxidant due to its α-hydroxycarbonyl group. Lactose is widely ingested through the milk and other unfermented dairy products and is considered to be one of the primary foods. On the other hand, lactose is also considered as one of the most widely used excipients for the development of pharmaceutical formulations. In this sense, lactose has been related to numerous drug-excipient or drug-food pharmacokinetic interactions. Intolerance, maldigestion and malabsorption of carbohydrates are common disorders in clinical practice, with lactose-intolerance being the most frequently diagnosed, afflicting 10% of the world's population. Four clinical subtypes of lactose intolerance may be distinguished, namely lactase deficiency in premature infants, congenital lactase deficiency, adult-type hypolactasia and secondary lactase intolerance. An overview of the main uses of lactose in human nutrition and in the pharmaceutical industry and the problems derived from this circumstance are described in this review.