Curriculum · Metabolic and Endocrine and Diabetes Mellitus
Homocystinuria and the marfanoid habitus
What it is
Homocystinuria is autosomal recessive and produces a marfanoid body habitus. Its main differential is Marfan syndrome, which is autosomal dominant. A marfanoid habitus is also part of MEN 2b. The three MEN groups are drawn as overlapping sets: pancreas and pituitary belong to MEN 1 alone, parathyroid lies in the overlap between MEN 1 and MEN 2a, pheochromocytoma and medullary thyroid lie in the overlap between MEN 2a and MEN 2b, and marfanoid habitus and neuromas belong to MEN 2b alone.
How it presents
The features common to both are pectus deformity, tall stature, a high arm to height ratio, a low upper to lower segment ratio, arachnodactyly, joint hyperlaxity, skin hyperelasticity and scoliosis. What sets homocystinuria apart is that it is autosomal recessive, with intellectual disability, thrombosis, downward lens dislocation, megaloblastic anemia and fair complexion. Marfan syndrome instead carries normal intellect, aortic root dilation and upward lens dislocation. Homocystinuria has no cardiac involvement, while Marfan syndrome brings aortic dilatation, dissection, AR and mitral valve prolapse. Homocystinuria also brings osteoporosis and recurrent thromboembolism, while flat feet, hernia and scoliosis fall on the Marfan side, together with a 50% reduction in life expectancy; scoliosis is counted among the overlapping features in one source and among the Marfan features in another. A worked example: a tall, fair-skinned and thin girl with hyperextensive skin and joint hyperlaxity who develops sudden-onset weakness and has developmental delay too.