Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Dec;86(6):2093–2098. doi: 10.1172/JCI114947

Familial hypercatabolic hypoproteinemia. A disorder of endogenous catabolism of albumin and immunoglobulin.

T A Waldmann 1, W D Terry 1
PMCID: PMC329849  PMID: 2254461

Abstract

The metabolism of albumin and IgG was investigated in two siblings, products of a first-cousin marriage, a female aged 34 yr and a male aged 17, who had a marked reduction in their respective serum concentrations of IgG (1.3 and 3.1 mg/ml) and albumin (19 and 21 mg/ml). The metabolism of radioiodinated IgG and albumin was studied in the two patients. The total circulating and body pools of IgG were less than 28% of normal. The IgG synthetic rates were within the normal range. However, the IgG survival was short, with their respective fractional catabolic rates increased fivefold to 31% and 36% of the intravenous pool per day (normal, 6.7 +/- 2%/d). Furthermore, the patients had reduced total body pools, normal synthetic rates, and increased fractional catabolic rates for albumin. There was no proteinuria or abnormality of renal or liver function. In addition, the patients did not have circulating antibodies directed toward IgG, IgA, or albumin. Furthermore, both patients had normal fecal 51Cr-labeled albumin tests, thus excluding excessive gastrointestinal protein loss. We propose that these siblings have a previously unrecognized familial disorder characterized by reduced serum concentrations of IgG and albumin caused by a defect in endogenous catabolism, leading to a short survival of these proteins that is associated in this family with chemical diabetes and a skeletal deformity.

Full text

PDF
2093

Images in this article

2095Image
on p.2095

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blaese R. M., Strober W., Brown R. S., Waldmann T. A. The Wiskott-Aldrich syndrome. A disorder with a possible defect in antigen processing or recognition. Lancet. 1968 May 18;1(7551):1056–1061. doi: 10.1016/s0140-6736(68)91411-6. [DOI] [PubMed] [Google Scholar]
  2. Blaese R. M., Strober W., Levy A. L., Waldmann T. A. Hypercatabolism of IgG, IgA, IgM, and albumin in the Wiskott-Aldrich syndrome. A unique disorder of serum protein metabolism. J Clin Invest. 1971 Nov;50(11):2331–2338. doi: 10.1172/JCI106731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. FAHEY J. L., MCKELVEY E. M. QUANTITATIVE DETERMINATION OF SERUM IMMUNOGLOBULINS IN ANTIBODY-AGAR PLATES. J Immunol. 1965 Jan;94:84–90. [PubMed] [Google Scholar]
  4. FAHEY J. L., SELL S. THE IMMUNOGLOBULINS OF MICE. V. THE METABOLIC (CATABOLIC) PROPERTIES OF FIVE IMMUNOGLOBULIN CLASSES. J Exp Med. 1965 Jul 1;122:41–58. doi: 10.1084/jem.122.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FARTHING C. P., GERWING J., SHEWELL J. The influence of the thyroid gland on the catabolism of 131I-labelled homologous gamma-globulin in the guinea-pig. J Endocrinol. 1960 Sep;21:91–96. doi: 10.1677/joe.0.0210091. [DOI] [PubMed] [Google Scholar]
  6. Levy A. L., Waldmann T. A. The effect of hydrocortisone on immunoglobulin metabolism. J Clin Invest. 1970 Sep;49(9):1679–1684. doi: 10.1172/JCI106385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. SOLOMON A., WALDMANN T. A., FAHEY J. L. Clinical and experimental metabolism of normal 6.6s gamma-globulin in normal subjects and in patients with macroglobulinemia and multiple myeloma. J Lab Clin Med. 1963 Jul;62:1–17. [PubMed] [Google Scholar]
  8. Strober W., Wochner R. D., Barlow M. H., McFarlin D. E., Waldmann T. A. Immunoglobulin metabolism in ataxia telangiectasia. J Clin Invest. 1968 Aug;47(8):1905–1915. doi: 10.1172/JCI105881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Strober W., Wochner R. D., Carbone P. P., Waldmann T. A. Intestinal lymphangiectasia: a protein-losing enteropathy with hypogammaglobulinemia, lymphocytopenia and impaired homograft rejection. J Clin Invest. 1967 Oct;46(10):1643–1656. doi: 10.1172/JCI105656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. WALDMANN T. A. Gastrointestinal protein loss demonstrated by Cr-51-labelled albumin. Lancet. 1961 Jul 15;2(7194):121–123. doi: 10.1016/s0140-6736(61)92646-0. [DOI] [PubMed] [Google Scholar]
  11. WALDMANN T. A., STEINFELD J. L., DUTCHER T. F., DAVIDSON J. D., GORDON R. S., Jr The role of the gastrointestinal system in "idiopathic hypoproteinemia". Gastroenterology. 1961 Sep;41:197–207. [PubMed] [Google Scholar]
  12. Waldmann T. A. Disorders of immunoglobulin metabolism. N Engl J Med. 1969 Nov 20;281(21):1170–1177. doi: 10.1056/NEJM196911202812107. [DOI] [PubMed] [Google Scholar]
  13. Waldmann T. A., Johnson J. S., Talal N. Hypogammaglobulinemia associated with accelerated catabolism of IgG secondary to its inteaction with an IgG-reactive monoclonal IgM. J Clin Invest. 1971 Apr;50(4):951–959. doi: 10.1172/JCI106567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Waldmann T. A. Protein-losing enteropathy. Gastroenterology. 1966 Mar;50(3):422–443. [PubMed] [Google Scholar]
  15. Waldmann T. A., Strober W. Metabolism of immunoglobulins. Prog Allergy. 1969;13:1–110. doi: 10.1159/000385919. [DOI] [PubMed] [Google Scholar]
  16. Wochner R. D., Drews G., Strober W., Waldmann T. A. Accelerated breakdown of immunoglobulin G (IgG) in myotonic dystrophy: a hereditary error of immunoglobulin catabolism. J Clin Invest. 1966 Mar;45(3):321–329. doi: 10.1172/JCI105346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wochner R. D. Hypercatabolism of normal IgG; an unexplained immunoglobulin abnormality in the connective tissue diseases. J Clin Invest. 1970 Mar;49(3):454–464. doi: 10.1172/JCI106254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wochner R. D., Weissman S. M., Waldmann T. A., Houston D., Berlin N. I. Direct measurement of the rates of synthesis of plasma proteins in control subjects and patients with gastrointestinal protein loss. J Clin Invest. 1968 May;47(5):971–982. doi: 10.1172/JCI105812. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES