Vascular and connective tissue features in 5 Italian patients with homocystinuria

Abstract

Homocystinuria is a metabolic disorder associated with defects in genes encoding for methionine metabolism enzymes. Vascular and connective tissue manifestations such as deep venous thrombosis, ectopia lentis and skeletal alterations are the major clinical features.We investigated the clinical manifestations of 5 Italian homocystinuric patients, performed mutation screening analysis on cystationine beta-synthase (CBS) gene and searched for genotype/phenotype correlations.We detected mild cardiovascular and skin connective tissue stigmas in these patients, never reported in homocystinuric patients before. We found 1 novel and 7 known mutations. Our patients carried no other mutation associated with venous thrombosis. Our data stress the importance of extending the clinical investigation for connective tissue manifestations in homocystinuric patients to all the organs/systems involved in Marfan syndrome, also suggesting long term follow-ups for cardiovascular manifestations.

Point-of-Care Ultrasonography Saves the Day in Dilated Cardiomyopathy: A Rare Presentation of Hyperhomocysteinemia

“…In addition, renal arterial pathology causing decreased elimination of homocysteine creates a self-perpetuation of cardiovascular risk [9]. Researchers have also reported fibrillin-1 protein modification causing alterations in connective tissues resulting in structural damages such as cardiac valvulopathies along with ocular and skeletal malformations, as seen in Marfan's syndrome [10]. This might have been the basis of the DCM seen in our case.…”

A Clinically Relevant Variant of the Human Hydrogen Sulfide‐Synthesizing Enzyme Cystathionine β‐Synthase: Increased CO Reactivity as a Novel Molecular Mechanism of Pathogenicity?

“…This prompted us to investigate in the present study a reportedly mild pathogenic mutation associated with classical homocystinuria, a proline-to-leucine substitution at residue 49 in human CBS [ 44 – 46 ]. The recombinant CBS p.P49L variant was expressed in E. coli , purified, and characterized both structurally and functionally.…”

“…The 146 C>T transition in exon 1 of the CBS gene generates the clinically relevant p.P49L variant, identified in patients with classical homocystinuria [ 44 – 46 ]. The mutation results in mild to moderate symptoms and sporadic responsiveness to vitamin B6 treatment.…”

Homocysteine may accelerate skin aging: A new chapter in the biology of skin senescence?

“…7 The skeletal manifestations of this disorder include osteoporosis and limitation of joint mobility, and its skin manifestations include thin, transparent skin and striae, which are the consequences of collagen underproduction. [8][9][10] Histomorphometric and histologic analyses revealed that CBS-deficient mice have wrinkled skin with thinning of the dermis. 10 Shuster 11 suggests that the changes in skin collagen correspond to changes in bone density.…”