Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystic fibrosis (CF) is associated with many clinical complications including steatosis for which the relation to defective CF transmembrane conductance regulator protein is unclear. Choline deficiency results in hepatic steatosis. Choline is the precursor of betaine, which donates methyl groups for remethylation of homocysteine to methionine and dimethylglycine. Previously, we have shown phospholipid malabsorption and increased plasma homocysteine in children with CF. In these studies we used normal phase HPLC with tandem mass spectrometry to determine plasma choline, betaine, and dimethylglycine in children with CF (n = 34) and healthy control children without CF (n = 15). Plasma choline, betaine, and dimethylglycine were significantly lower in children with CF (means +/- SEM, 6.48 +/- 0.35, 23.8 +/- 1.49, 1.49 +/- 0.13 mumol/L, respectively) than in children without CF (8.98 +/- 0.46, 37.3 +/- 1.84, 3.01 +/- 0.17 mumol/L, respectively). Plasma choline (r = 0.373, P = 0.007) and betaine (r = 0.399, P = 0.005) were positively related to methionine, and choline was inversely related to homocysteine (r = -0.316, P = 0.03). Choline, betaine, and dimethylglycine were all significantly and positively related to the plasma S-adenosylmethionine:S-adenosylhomocysteine (SAM:SAH) ratio (r = 0.294, r = 0.377, r = 0.442, respectively; P < 0.05). The plasma choline:betaine and betaine:dimethylglycine ratios did not differ between the children with CF and the control children, suggesting no increase in betaine synthesis, or betaine-dependent remethylation of homocysteine. These studies suggest that choline depletion may contribute to increased homocysteine in children with CF. Choline depletion and altered thiol metabolism may contribute to the clinical complications associated with CF.
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PMID:Evidence of choline depletion and reduced betaine and dimethylglycine with increased homocysteine in plasma of children with cystic fibrosis. 1685 45

Monoallelic desmoglein 1 mutations have been known for many years to cause striate palmoplantar keratoderma, but only recently, biallelic loss-of-function mutations were associated with a new disorder, designated as SAM syndrome (comprising severe dermatitis, multiple allergies and metabolic wasting) in two consanguineous families. We report on a new case from a third independent family with the homozygous nonsense mutation, c.2659C>T, p.R887* in exon 15 of DSG1 (desmoglein 1 gene). This mutation led to mRNA decay and loss of expression of desmoglein 1. The clinical phenotype consisted of severe palmoplantar keratoderma, dermatitis and multiple allergies. In contrast to the previous cases, malabsorption, hypoalbuminaemia, developmental delay, hypotrichosis or severe recurrent infections were not observed.
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PMID:Loss of desmoglein 1 associated with palmoplantar keratoderma, dermatitis and multiple allergies. 2504 Oct 99

Treating patients with genodermatoses is challenging because of the chronic disease course and of limited available therapies. We report on the efficacy of secukinumab for the treatment of a genodermatosis caused by biallelic loss-of-function mutations in the desmoglein 1 gene (DSG1), the SAM syndrome. The SAM syndrome comprises severe dermatitis, multiple allergies and metabolic wasting and it can manifest as ichthyosiform erythroderma at birth.1 Additional variable features are palmoplantar keratoderma, hypotrichosis, recurrent skin infections, malabsorption and failure to thrive.2.
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PMID:Secukinumab for the treatment of SAM syndrome associated with desmoglein-1 deficiency. 3320 94