Thrombomodulin and ristocetincofactor in homocystinuria: A study in two siblings

Schienle, Hans Wolfgang; Seitz, Rainer; Nawroth, Peter P.; Rohner, Iris; Lerch, L; Krumpholz, Barbara; G, Krauss; Fowler, Brian; Baumgartner, R.; Willenbockel, U.; Egbring, R

doi:10.1016/0049-3848(95)90867-f

Cited by 6 publications

(9 citation statements)

References 17 publications

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“…Furthermore, the TM plasma levels decreased significantly, from 57.1 to 49.0 ng/ml, under vitamin therapy (53). This leads to the speculation that Hey might directly participate in vascular damage and TM release, as suggested in patients with hyperhomocysteinuria (54). Therefore, we studied the Hcy-induced TM release in an endothelial cell culture system.…”

Section: Conclusion-mentioning

confidence: 97%

Hyperhomocyst(e)inemia and Endothelial Dysfunction in IDDM

Hofmann

Kohl²,

Zumbach³

et al. 1998

Diabetes Care

146

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Section: Conclusion-mentioning

confidence: 97%

Hyperhomocyst(e)inemia and Endothelial Dysfunction in IDDM

Hofmann

Kohl²,

Zumbach³

et al. 1998

Diabetes Care

146

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“…Raised Hcy concentrations modify sulfhydryl groups on proteins and interfere with the cross-linking of sulfhydryl groups in proteins such as elastin; this is thought to cause the lens dislocation and skeletal abnormalities. Raised Hcy concentrations also alter intracellular signaling and cause endoplasmic reticulum stress with endothelial dysfunction (Schienle et al 1995; Lai and Kan 2015); these mechanisms together with impaired thrombolysis may be responsible for thromboembolism and vascular disease (Schienle et al 1994). Increased SAH impairs methylation reactions and decreased cystathionine and cysteine are associated with apoptosis, oxidative stress and alterations of structural proteins such as fibrillin, which may contribute to connective tissue abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Guidelines for the diagnosis and management of cystathionine beta‐synthase deficiency

Morris

Kožich

Santra

et al. 2016

J of Inher Metab Disea

270

360

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Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyridoxine. In this article, we present recommendations for the diagnosis and management of CBS deficiency, based on a systematic review of the literature. Unfortunately, the quality of the evidence is poor, as it often is for rare diseases. We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. Our recommendations may help to standardise testing for pyridoxine responsiveness. Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 μmol/L. Nevertheless, we recommend keeping the concentration below 100 μmol/L because levels fluctuate and the complications associated with high levels are so serious.

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“…This build-up could lead to several complications such as nearsightedness and dislocated eye lenses. In addition, the raised homocysteine levels could alter the intracellular signaling and cause endoplasmic reticulum stress with endothelial dysfunction [4,5]. Consequently, leading to thromboembolism, vascular, and other diseases [6].…”

Section: Introductionmentioning

confidence: 99%

The Spectrum of Mutations of Homocystinuria in the MENA Region

Al-Sadeq

Nasrallah

2020

Genes

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Homocystinuria is an inborn error of metabolism due to the deficiency in cystathionine beta-synthase (CBS) enzyme activity. It leads to the elevation of both homocysteine and methionine levels in the blood and urine. Consequently, this build-up could lead to several complications such as nearsightedness, dislocated eye lenses, a variety of psychiatric and behavioral disorders, as well as vascular system complications. The prevalence of homocystinuria is around 1/200,000 births worldwide. However, its prevalence in the Gulf region, notably Qatar, is exceptionally high and reached 1:1800. To date, more than 191 pathogenic CBS mutations have been documented. The majority of these mutations were identified in Caucasians of European ancestry, whereas only a few mutations from African-Americans or Asians were reported. Approximately 87% of all CBS mutations are missense and do not target the CBS catalytic site, but rather result in unstable misfolded proteins lacking the normal biological function, designating them for degradation. The early detection of homocystinuria along with low protein and methionine-restricted diet is the best treatment approach for all types of homocystinuria patients. Yet, less than 50% of affected individuals show a significant reduction in plasma homocysteine levels after treatment. Patients who fail to lower the elevated homocysteine levels, through high protein-restricted diet or by B6 and folic acid supplements, are at higher risk for cardiovascular diseases, neurodegenerative diseases, neural tube defects, and other severe clinical complications. This review aims to examine the mutations spectrum of the CBS gene, the disease management, as well as the current and potential treatment approaches with a greater emphasis on studies reported in the Middle East and North Africa (MENA) region.

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Thrombomodulin and ristocetincofactor in homocystinuria: A study in two siblings

Cited by 6 publications

References 17 publications

Hyperhomocyst(e)inemia and Endothelial Dysfunction in IDDM

Hyperhomocyst(e)inemia and Endothelial Dysfunction in IDDM

Guidelines for the diagnosis and management of cystathionine beta‐synthase deficiency

The Spectrum of Mutations of Homocystinuria in the MENA Region

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