COLACD
MCID: LCT013
MIFTS: 45

Lactase Deficiency, Congenital (COLACD)

Categories: Gastrointestinal diseases, Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Lactase Deficiency, Congenital

MalaCards integrated aliases for Lactase Deficiency, Congenital:

Name: Lactase Deficiency, Congenital 56 13 54 43 39 71
Congenital Lactase Deficiency 12 52 58 73 36 29 6 15 32
Disaccharide Intolerance Ii 56 12 73
Congenital Lactose Malabsorption 12
Congenital Lactose Intolerance 12
Congenital Alactasia Syndrome 12
Alactasia, Congenital 56
Congenital Alactasia 12
Hereditary Alactasia 73
Colacd 73
Cld 12

Characteristics:

Orphanet epidemiological data:

58
congenital lactase deficiency
Inheritance: Autosomal recessive;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
increased frequency in finland (incidence 1:60,000 finnish newborns)
onset day of life 1-10 in infants fed lactose-containing milk


HPO:

31
lactase deficiency, congenital:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare gastroenterological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111646
OMIM 56 223000
KEGG 36 H00116
MeSH 43 C562600
SNOMED-CT 67 5388008
ICD10 32 E73.0
ICD10 via Orphanet 33 E73.0
UMLS via Orphanet 72 C0268179
Orphanet 58 ORPHA53690
MedGen 41 C0268179
UMLS 71 C0268179

Summaries for Lactase Deficiency, Congenital

UniProtKB/Swiss-Prot : 73 Congenital lactase deficiency: Autosomal recessive, rare and severe gastrointestinal disorder. It is characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. An almost total lack of LCT activity is found in jejunal biopsy material of patients with congenital lactase deficiency. Opposite to congenital lactase deficiency, also known as lactose intolerance, is the most common enzyme deficiency worldwide. It is caused by developmental down- regulation of lactase activity during childhood or early adulthood. The decline of lactase activity is a normal physiological phenomenon; however, the majority of Northern Europeans have the ability to maintain lactase activity and digest lactose throughout life (lactase persistence). The down-regulation of lactase activity operates at the transcriptional level and it is associated with a noncoding variation in the MCM6 gene, located in the upstream vicinity of LCT.

MalaCards based summary : Lactase Deficiency, Congenital, also known as congenital lactase deficiency, is related to lipase deficiency, combined and congenital chloride diarrhea. An important gene associated with Lactase Deficiency, Congenital is LCT (Lactase), and among its related pathways/superpathways are Galactose metabolism and Toll-like Receptor Signaling Pathway. Affiliated tissues include breast, small intestine and thyroid, and related phenotypes are dehydration and metabolic acidosis

Disease Ontology : 12 A carbohydrate metabolic disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas that has material basis in homozygous or compound heterozygous mutation in LCT on chromosome 2q21.3.

OMIM : 56 Congenital lactase deficiency is a severe gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas. (223000)

KEGG : 36 Congenital lactase deficiency is an autosomal recessive disorder caused by enzyme deficiency for metabolizing lactose.

Related Diseases for Lactase Deficiency, Congenital

Graphical network of the top 20 diseases related to Lactase Deficiency, Congenital:



Diseases related to Lactase Deficiency, Congenital

Symptoms & Phenotypes for Lactase Deficiency, Congenital

Human phenotypes related to Lactase Deficiency, Congenital:

31
# Description HPO Frequency HPO Source Accession
1 dehydration 31 HP:0001944
2 metabolic acidosis 31 HP:0001942
3 diarrhea 31 HP:0002014
4 lactose intolerance 31 HP:0004789
5 decreased small intestinal mucosa lactase level 31 HP:0025130

Symptoms via clinical synopsis from OMIM:

56
Metabolic Features:
dehydration
metabolic acidosis

Laboratory Abnormalities:
decreased-absent intestinal mucosa lactase activity
normal maltase, isomaltase, and sucrase activity

Abdomen Gastrointestinal:
neonatal diarrhea

Clinical features from OMIM:

223000

Drugs & Therapeutics for Lactase Deficiency, Congenital

Search Clinical Trials , NIH Clinical Center for Lactase Deficiency, Congenital

Cochrane evidence based reviews: lactase deficiency, congenital

Genetic Tests for Lactase Deficiency, Congenital

Genetic tests related to Lactase Deficiency, Congenital:

# Genetic test Affiliating Genes
1 Congenital Lactase Deficiency 29 LCT

Anatomical Context for Lactase Deficiency, Congenital

MalaCards organs/tissues related to Lactase Deficiency, Congenital:

40
Breast, Small Intestine, Thyroid

Publications for Lactase Deficiency, Congenital

Articles related to Lactase Deficiency, Congenital:

(show all 44)
# Title Authors PMID Year
1
Mutations in the translated region of the lactase gene (LCT) underlie congenital lactase deficiency. 61 54 56 6
16400612 2006
2
Assignment of the locus for congenital lactase deficiency to 2q21, in the vicinity of but separate from the lactase-phlorizin hydrolase gene. 61 56
9758622 1998
3
Congenital lactase deficiency. A clinical study on 16 patients. 56 61
6847226 1983
4
Identification of a variant associated with adult-type hypolactasia. 56
11788828 2002
5
High frequency of lactose absorbers among adults with idiopathic senile and presenile cataract in a population with a high prevalence of primary adult lactose malabsorption. 56
6141422 1984
6
Severe lactose intolerance with lactosuria and vomiting. 56
7416780 1980
7
Lactose intolerance associated with cataracts. 56
759181 1979
8
Congenital lactose intolerance of gastrogen origin associated with cataracts. 56
4209121 1974
9
Congenital lactose malabsorption. 56
5419986 1970
10
Severe familial lactose intolerance--a gastrogen disorder? 56
5365173 1969
11
Specificity of the human intestinal disaccharidases and implications for hereditary disaccharide intolerance. 56
13883118 1962
12
Lactosuria and amino-aciduria in infancy. A new inborn error of metabolism? 56
13814131 1960
13
Defective lactose absorption causing malnutrition in infancy. 56
13665980 1959
14
[Idiopathic lactosuria in a patient of chronic diarrhea and acidosis]. 56
13565838 1958
15
[Congenital lactase deficiency--a more common disease than previously thought?]. 54 61
19432082 2009
16
Four novel mutations in the lactase gene (LCT) underlying congenital lactase deficiency (CLD). 54 61
19161632 2009
17
Molecular differentiation of congenital lactase deficiency from adult-type hypolactasia. 61 54
17345962 2007
18
Human Health Effects of Lactose Consumption as a Food and Drug Ingredient. 61
32048961 2020
19
Congenital Lactase Deficiency: Mutations, Functional and Biochemical Implications, and Future Perspectives. 61
30813293 2019
20
A novel mutation within the lactase gene (LCT): the first report of congenital lactase deficiency diagnosed in Central Europe. 61
26215149 2015
21
[Congenital lactase deficiency: Identification of a new mutation]. 61
25468453 2015
22
Congenital lactose intolerance is triggered by severe mutations on both alleles of the lactase gene. 61
25881162 2015
23
Lactose intolerance. 61
26715083 2015
24
Two novel mutations in the lactase gene in a Japanese infant with congenital lactase deficiency. 61
22688420 2012
25
Selected disorders of malabsorption. 61
21872088 2011
26
Impaired trafficking and subcellular localization of a mutant lactase associated with congenital lactase deficiency. 61
19208354 2009
27
Infant formula. 61
19378873 2009
28
Molecular genetics of human lactase deficiencies. 61
19639477 2009
29
Lactose malabsorption. 61
21063860 2008
30
First reported case of lysinuric protein intolerance (LPI) in Lithuania, confirmed biochemically and by DNA analysis. 61
17666782 2007
31
Congenital maltase-glucoamylase deficiency associated with lactase and sucrase deficiencies. 61
12394387 2002
32
Congenital sucrase-isomaltase deficiency presenting with failure to thrive, hypercalcemia, and nephrocalcinosis. 61
12014995 2002
33
[Intestinal microbiocenosis in children with intestinal enzymopathy]. 61
11550576 2001
34
Molecular and cellular aspects and regulation of intestinal lactase-phlorizin hydrolase. 61
11332711 2001
35
Sequence, structural, functional, and phylogenetic analyses of three glycosidase families. 54
9779294 1998
36
Hypercalcemia and nephrocalcinosis in patients with congenital lactase deficiency. 61
8523189 1995
37
Clinical picture of hypolactasia and lactose intolerance. 61
8042017 1994
38
Clinical significance of enzymatic deficiencies in the gastrointestinal tract with particular reference to lactase deficiency. 61
6439079 1984
39
Use of lactose-hydrolyzed human milk in congenital lactase deficiency. 61
7119963 1982
40
Morphometric study of the jejunal mucosa in various childhood enteropathies with special reference to intraepithelial lymphocytes. 61
7186067 1982
41
Thyrotoxicosis in a neonate of a mother with no history of thyroid disease. 61
1275545 1976
42
[Malabsorption of carbohydrates in children (author's transl)]. 61
238444 1975
43
Intestinal beta-galactosidases in adult low lactase activity and in congenital lactase deficiency. 61
4852526 1974
44
Congenital lactase deficiency. 61
5946649 1966

Variations for Lactase Deficiency, Congenital

ClinVar genetic disease variations for Lactase Deficiency, Congenital:

6 (show top 50) (show all 121) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LCT NM_002299.4(LCT):c.4170T>A (p.Tyr1390Ter)SNV Pathogenic 6586 rs121908936 2:136564701-136564701 2:135807131-135807131
2 LCT LCT, 4-BP DEL, NT4998deletion Pathogenic 6587
3 LCT NM_002299.4(LCT):c.804G>C (p.Gln268His)SNV Pathogenic 6588 rs121908937 2:136587163-136587163 2:135829593-135829593
4 LCT NM_002299.4(LCT):c.1692_1696del (p.Val565fs)deletion Likely pathogenic 56387 rs386833832 2:136574922-136574926 2:135817352-135817356
5 LCT NM_002299.4(LCT):c.4087G>A (p.Gly1363Ser)SNV Likely pathogenic 56388 rs386833833 2:136564784-136564784 2:135807214-135807214
6 LCT NM_002299.4(LCT):c.4419C>G (p.Tyr1473Ter)SNV Likely pathogenic 56389 rs386833834 2:136562382-136562382 2:135804812-135804812
7 LCT NM_002299.4(LCT):c.4834G>T (p.Glu1612Ter)SNV Likely pathogenic 56390 rs386833835 2:136558209-136558209 2:135800639-135800639
8 LCT NM_002299.4(LCT):c.4998_5001del (p.Ser1666fs)deletion Likely pathogenic 56391 rs386833836 2:136552321-136552324 2:135794751-135794754
9 LCT NM_002299.4(LCT):c.5387del (p.Asp1796fs)deletion Likely pathogenic 56392 rs386833837 2:136547317-136547317 2:135789747-135789747
10 LCT NM_002299.4(LCT):c.649_650CT[2] (p.Ser218fs)short repeat Likely pathogenic 56393 rs386833838 2:136590747-136590748 2:135833177-135833178
11 LCT NM_002299.4(LCT):c.4347T>C (p.Phe1449=)SNV Conflicting interpretations of pathogenicity 331175 rs17699796 2:136562454-136562454 2:135804884-135804884
12 LCT NM_002299.4(LCT):c.4173+6_4173+8delshort repeat Conflicting interpretations of pathogenicity 331178 rs375300532 2:136564690-136564692 2:135807120-135807122
13 LCT NM_002299.4(LCT):c.2763G>A (p.Ala921=)SNV Conflicting interpretations of pathogenicity 331193 rs116951780 2:136567154-136567154 2:135809584-135809584
14 LCT NM_002299.4(LCT):c.*325G>CSNV Conflicting interpretations of pathogenicity 331156 rs62170085 2:136545569-136545569 2:135787999-135787999
15 LCT NM_002299.4(LCT):c.4576C>T (p.Leu1526=)SNV Conflicting interpretations of pathogenicity 331173 rs140074771 2:136561587-136561587 2:135804017-135804017
16 LCT NM_002299.4(LCT):c.1113G>A (p.Arg371=)SNV Conflicting interpretations of pathogenicity 729578 2:136575505-136575505 2:135817935-135817935
17 LCT NM_002299.4(LCT):c.4026G>A (p.Thr1342=)SNV Conflicting interpretations of pathogenicity 331180 rs150640616 2:136564845-136564845 2:135807275-135807275
18 LCT NM_002299.4(LCT):c.2760C>T (p.Gly920=)SNV Conflicting interpretations of pathogenicity 331194 rs200579267 2:136567157-136567157 2:135809587-135809587
19 LCT NM_002299.4(LCT):c.2457C>T (p.His819=)SNV Uncertain significance 331196 rs149425549 2:136567460-136567460 2:135809890-135809890
20 LCT NM_002299.4(LCT):c.1396G>T (p.Gly466Trp)SNV Uncertain significance 331203 rs377102890 2:136575222-136575222 2:135817652-135817652
21 LCT NM_002299.4(LCT):c.4122C>T (p.Tyr1374=)SNV Uncertain significance 331179 rs557321611 2:136564749-136564749 2:135807179-135807179
22 LCT NM_002299.4(LCT):c.319G>A (p.Glu107Lys)SNV Uncertain significance 331212 rs761296720 2:136594421-136594421 2:135836851-135836851
23 LCT NM_002299.4(LCT):c.54G>C (p.Trp18Cys)SNV Uncertain significance 331214 rs886054870 2:136594686-136594686 2:135837116-135837116
24 LCT NM_002299.4(LCT):c.3759G>A (p.Thr1253=)SNV Uncertain significance 331183 rs764860323 2:136566158-136566158 2:135808588-135808588
25 LCT NM_002299.4(LCT):c.3599C>T (p.Thr1200Met)SNV Uncertain significance 331184 rs148317168 2:136566318-136566318 2:135808748-135808748
26 LCT NM_002299.4(LCT):c.3341A>G (p.Gln1114Arg)SNV Uncertain significance 331188 rs148838160 2:136566576-136566576 2:135809006-135809006
27 LCT NM_002299.4(LCT):c.1780C>G (p.Gln594Glu)SNV Uncertain significance 331199 rs886054867 2:136570454-136570454 2:135812884-135812884
28 LCT NM_002299.4(LCT):c.2177G>A (p.Arg726His)SNV Uncertain significance 331197 rs886054866 2:136570057-136570057 2:135812487-135812487
29 LCT NM_002299.4(LCT):c.1902C>T (p.Pro634=)SNV Uncertain significance 331198 rs202014246 2:136570332-136570332 2:135812762-135812762
30 LCT NM_002299.4(LCT):c.4646A>G (p.Tyr1549Cys)SNV Uncertain significance 331171 rs147495948 2:136561517-136561517 2:135803947-135803947
31 LCT NM_002299.4(LCT):c.*251G>ASNV Uncertain significance 331157 rs886054860 2:136545643-136545643 2:135788073-135788073
32 LCT NM_002299.4(LCT):c.*10A>CSNV Uncertain significance 331160 rs200994158 2:136545884-136545884 2:135788314-135788314
33 LCT NM_002299.4(LCT):c.5771T>C (p.Val1924Ala)SNV Uncertain significance 331161 rs886054861 2:136545907-136545907 2:135788337-135788337
34 LCT NM_002299.4(LCT):c.5656G>A (p.Val1886Ile)SNV Uncertain significance 331163 rs376732886 2:136546022-136546022 2:135788452-135788452
35 LCT NM_002299.4(LCT):c.5493C>T (p.Tyr1831=)SNV Uncertain significance 331166 rs369410973 2:136547211-136547211 2:135789641-135789641
36 LCT NM_002299.4(LCT):c.4239A>G (p.Pro1413=)SNV Uncertain significance 331177 rs752925060 2:136562562-136562562 2:135804992-135804992
37 LCT NM_002299.4(LCT):c.3986C>T (p.Thr1329Met)SNV Uncertain significance 331181 rs555708380 2:136564885-136564885 2:135807315-135807315
38 LCT NM_002299.4(LCT):c.3595G>A (p.Ala1199Thr)SNV Uncertain significance 331185 rs886054863 2:136566322-136566322 2:135808752-135808752
39 LCT NM_002299.4(LCT):c.3532C>T (p.Leu1178=)SNV Uncertain significance 331186 rs886054864 2:136566385-136566385 2:135808815-135808815
40 LCT NM_002299.4(LCT):c.3390G>A (p.Glu1130=)SNV Uncertain significance 331187 rs886054865 2:136566527-136566527 2:135808957-135808957
41 LCT NM_002299.4(LCT):c.*275A>GSNV Uncertain significance 894022 2:136545619-136545619 2:135788049-135788049
42 LCT NM_002299.4(LCT):c.*239C>TSNV Uncertain significance 894023 2:136545655-136545655 2:135788085-135788085
43 LCT NM_002299.4(LCT):c.4760G>A (p.Arg1587His)SNV Uncertain significance 631827 rs146614143 2:136558283-136558283 2:135800713-135800713
44 LCT NM_002299.4(LCT):c.1539G>A (p.Glu513=)SNV Uncertain significance 893076 2:136575079-136575079 2:135817509-135817509
45 LCT NM_002299.4(LCT):c.1116G>A (p.Ala372=)SNV Uncertain significance 893077 2:136575502-136575502 2:135817932-135817932
46 LCT NM_002299.4(LCT):c.1004C>G (p.Thr335Ser)SNV Uncertain significance 893283 2:136575614-136575614 2:135818044-135818044
47 LCT NM_002299.4(LCT):c.840C>T (p.Asn280=)SNV Uncertain significance 893284 2:136581538-136581538 2:135823968-135823968
48 LCT NM_002299.4(LCT):c.725C>T (p.Thr242Met)SNV Uncertain significance 893285 2:136587242-136587242 2:135829672-135829672
49 LCT NM_002299.4(LCT):c.677T>C (p.Ile226Thr)SNV Uncertain significance 893286 2:136590724-136590724 2:135833154-135833154
50 LCT NM_002299.4(LCT):c.280G>A (p.Ala94Thr)SNV Uncertain significance 894134 2:136594460-136594460 2:135836890-135836890

UniProtKB/Swiss-Prot genetic disease variations for Lactase Deficiency, Congenital:

73
# Symbol AA change Variation ID SNP ID
1 LCT p.Gln268His VAR_026706 rs121908937
2 LCT p.Gly1363Ser VAR_026708 rs386833833

Expression for Lactase Deficiency, Congenital

Search GEO for disease gene expression data for Lactase Deficiency, Congenital.

Pathways for Lactase Deficiency, Congenital

Pathways related to Lactase Deficiency, Congenital according to KEGG:

36
# Name Kegg Source Accession
1 Galactose metabolism hsa00052

Pathways related to Lactase Deficiency, Congenital according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.74 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
2
Show member pathways
12.62 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
3
Show member pathways
12.39 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
4
Show member pathways
12.3 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
5
Show member pathways
12.26 CLDN7 CLDN4 CLDN3 CLDN1
6 11.94 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
7 11.76 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
8 11.52 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
9
Show member pathways
11.17 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
10 10.98 CLDN3 CLDN1

GO Terms for Lactase Deficiency, Congenital

Cellular components related to Lactase Deficiency, Congenital according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 10.1 TSPAN4 TMX1 LMF2 LMF1 LCT GAL3ST3
2 apicolateral plasma membrane GO:0016327 9.43 CLDN7 CLDN4 CLDN3
3 bicellular tight junction GO:0005923 9.35 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
4 tight junction GO:0070160 9.33 CLDN4 CLDN3 CLDN1
5 lateral plasma membrane GO:0016328 9.02 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1

Biological processes related to Lactase Deficiency, Congenital according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 cell adhesion GO:0007155 9.83 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
2 response to ethanol GO:0045471 9.58 CLDN7 CLDN3 CLDN1
3 maintenance of permeability of blood-brain barrier GO:0035633 9.51 CLDN3 CLDN1
4 regulation of cell morphogenesis GO:0022604 9.49 CLDN4 CLDN3
5 establishment of skin barrier GO:0061436 9.48 CLDN4 CLDN1
6 protein maturation GO:0051604 9.46 LMF2 LMF1
7 positive regulation of metallopeptidase activity GO:1905050 9.37 CLDN4 CLDN3
8 bicellular tight junction assembly GO:0070830 9.35 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
9 positive regulation of wound healing GO:0090303 9.33 CLDN4 CLDN3 CLDN1
10 positive regulation of bicellular tight junction assembly GO:1903348 9.32 CLDN3 CLDN1
11 cell junction maintenance GO:0034331 9.26 CLDN3 CLDN1
12 calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules GO:0016338 9.02 CLDN7 CLDN4 CLDN3 CLDN15 CLDN1

Molecular functions related to Lactase Deficiency, Congenital according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 9.43 CRYAA CLDN7 CLDN4 CLDN3 CLDN15 CLDN1
2 structural molecule activity GO:0005198 9.1 CRYAA CLDN7 CLDN4 CLDN3 CLDN15 CLDN1

Sources for Lactase Deficiency, Congenital

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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