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The Marfan syndrome was described as dolichostenomelia in 1886 by Marfan (Marfan 1886). McKusick (McKusick 1972) recognized it as a connective tissue disorder. In 1972 two cases of Marfan syndrome associated with "juvenile diabetes mellitus" were observed by McKusick, who considered this association as accidental.
When we entered the key words: Marfan syndrome – diabetes mellitus type 1 into online literature search engine Pub Med, we obtained only one report from 1992 of a Japanese 3-year old girl with association of these two conditions (Yamamoto et al. 1992). As far as we know, it was the third reported case so far. The relationship between these two conditions remains unclear.
We report here on an observation of the association of Marfan syndrome with type 1 diabetes mellitus in a now 34 year old man.
He was diagnosed at the age of 18 as suffering from Marfan syndrome and registered in the department of Medical Genetics at the University Hospital in Pilsen. The condition was also found in his father and in one brother. The diagnosis was done from anthropometrical measurements, notably: body height 198 cm, length of extremities 120 cm, torso
– length 78 cm (index 1,53 i.e. > 1,05), stretched arms – span 207 cm, index: arm
– span/height = 1,045 (borderline significance). Metacarpal index 8,9 (i.e. positive). Scoliosis 20 degree by Cobb, protrusion of acetabula on X-ray of pelvic bones. The test thumb
– wrist was also positive. Ultrasonography of occular bulb-length was 23,5 mm bilaterally. Echokardiografy revealed a slight mitral regurgitation.
At the age of 34 years he presented with sudden onset of polydipsia and polyuria and weight loss of 7 kg. These symptoms appeared about two weeks after an unspecified viral infection. A hyperglycemia 18,9 mmol/l was ascertained. Low blood C peptide concentrations (0,69 µg/l); aGAD (autoantibodies glutamic acid decarboxylase) 49,4; aIRI (autoantibodies insulin) 4,8; aLO (autoantibodies islets of Langerhans) 7,9, proved conclusive for the diagnosis of type 1 diabetes mellitus.
The patient is being treated by an intensified insulin regime in continuous subcutaneous insulin infusion, so far without any clinical complications.
The association between Marfan syndrome and type 1 diabetes mellitus is a rare. It may occur only accidentally. However, a common genetic or immunological pathway may exist. Marfan syndrome is a disorder of connective tissue, caused by a mutation in fibrillin-1, associated with a disregulation of transforming growth factor beta (TGF) activation and signaling. Because of TGF-beta was found to have several immunologic effects, its deficiency may probably contribute to the patogenesis of type 1 diabetes mellitus (Kaartinen et al. 2003; Neptune et al. 2003; Azar et al. 2000).
This idea will require more case studies to enable an assessment of the causal association or linkage study of sharing genetic loci in a family where both these conditions, Marfan syndrome and type 1 diabetes mellitus occur.
References:
Azar, S. T., Salti, I., Zatnout, M. S. et al. Alterations in Plasma Transforming Growth Factor beta in Normoalbuminuric Type 1 and Type 2 Diabetic Patiens. J Clin Endocrin and Metab 85: 4680, 2000.
Kaartinen, V., Warburton, D. Fibrillin controls TGF-beta activation. Nature Genetics 33: 331 - 332, 2003.
Marfan, A. B. Un cas de deformation congenitale des quarte members plus prononcee aux extremites characterisee par l´allongement des os avec un certain degre d´amincissement. Bull Mem Soc Med Hop 13: 220 - 226, 1886. (in French)
McKusick, V. A. The Marfan syndrome. In: Heritable Disorders of Connective Tissue, 4th ed. St. Louis: CV Mosby Co, 1972. (p. 61 - 223)
Neptune, E. R., Frischmeyer, P. A., Arkány, D. E. et al. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nature Genet 33: 407 - 411, 2003.
Yamamoto, T., Inoue, F., Matsumura, A. et al. Report of a Japanese girl with Marfan syndrome associated with insulin-dependent diabetes mellitus. Acta Pediatr Jpn 34: 551 - 553, 1992.
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