| #241600 | ||||||||||||
| HYPOPROTEINEMIA, HYPERCATABOLIC | ||||||||||||
| Phenotype Gene Relationships | ||||||||||||
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| Clinical Synopsis | ||||||||||||
| TEXT | ||||||||||||
| A number sign (#) is used with this entry because hypercatabolic hypoproteinemia is caused by mutation in the gene encoding beta-2-microglobulin (B2M; 109700). | ||||||||||||
| Clinical Features | ||||||||||||
| Waldmann et al. (1968), Waldmann (1969), and Waldmann and Terry (1990) investigated a 34-year-old woman and her 17-year-old brother, products of a first-cousin marriage, who had marked reduction in serum concentrations of immunoglobulin and albumin (ALB; 103600). The total circulating and body pools of IgG were less than 28% of normal, although the IgG synthetic rates were in the normal range. IgG survival was short, with a 5-fold increase in catabolic rate. There was proteinuria or abnormality of renal or liver function and no circulating antibodies directed against either immunoglobulin or albumin. Furthermore, Waldmann and Terry (1990) excluded excessive gastrointestinal protein loss by normal fecal (51)Cr-labeled albumin tests. The hypercatabolic hypoproteinemia was associated with chemical diabetes mellitus and a skeletal deformity, i.e., shortened ulnae and bowed radii. | ||||||||||||
| Molecular Genetics | ||||||||||||
| In the 2 sibs reported by Waldmann (1969), Wani et al. (2006) identified a homozygous mutation in the B2M gene (109700.0001). Both sibs had B2M serum levels that were less than 1.0% of normal as well as soluble HLA levels that were less than 0.2% of normal. The neonatal Fc receptor (FcRn) is a heterodimer of a nonclassical MHC class I alpha chain (FCGRT; 601437) and B2M that binds the 2 most abundant serum proteins, IgG and albumin, after their constitutive cellular uptake. FcRn binds both proteins, thus acting as a salvage pathway, protecting them from lysosomal degradation and extending the catabolic half-lives of both proteins. In these sibs, deficiency of B2M and subsequent deficiency of FcRn resulted in increased catabolism of serum proteins. | ||||||||||||
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