A Case of Homocystinuria with a Dystonic Neurological Syndrome

Hagberg, B; Hambræus, Leif; Bensch, Kenneth G.

doi:10.1055/s-0028-1091823

Cited by 21 publications

(10 citation statements)

References 1 publication

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“…Thus, the frequency of ectopic lenses increases from 38% at the age of 5 years to 90% 20 years later (Cross & Jensen 1973). Unfortunately, this process is not halted by normalization of the amino acid profile as demonstrated by Hagberg et al (1970). In accordance with this, the lens ectopia also progressed in our case 1 under regular pyridoxine treatment and normal plasma amino acid pattern.…”

Section: Discussionsupporting

confidence: 86%

Homocystinuria Treated With Pyridoxine

Blika¹,

Saunte²,

Lunde³

et al. 1982

Acta Ophthalmologica

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Four cases of homocystinuria with lens luxation have been examined. As judged from the plasma amino acid pattern, they all responded well on pyridoxine treatment. Two of them discontinued the treatment on their own, and one of these died at the age of 17 years. The lens luxation progressed in one case despite adequate treatment. Scanning electron microscopy of one lens revealed partly broken zonules, abnormal zonular attachment, and a spongy appearance of the capsule proper. Hoping that adequate treatment will reduce more serious complications such as thromboembolism in these patients, it is concluded that an early diagnosis largely depends on the ophthalmologist, who should perform the silver-nitroprusside test, specific for homocystinuria, in all patients with non traumatic lens luxation.

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Section: Discussionsupporting

confidence: 86%

Homocystinuria Treated With Pyridoxine

Blika¹,

Saunte²,

Lunde³

et al. 1982

Acta Ophthalmologica

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“…A large amount of protein-bound homocyst(e)ine was also demonstrated in the brain, liver and kidney of homocystinuric patients. These observations might account for the findings that some clinical abnormalities such as ectopia lentis and abnormal morphology in the hepatocytes persisted or developed in pyridoxine responsive homocystinuric patients despite the absence of free homocystine in their tissue fluids (4,5,7). We postulated that the formation of protein-bound homocyst(e)ine might be responsible for the direct damaging effect of homocystine on the vascular endothelium and other tissues.…”

Section: Discussionmentioning

confidence: 93%

The Effect of D-Penicillamine on Protein-Bound Homocyst(e)ine in Homocystinurics

1982

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SummaryThere is considerable evidence that homocystine has a direct damaging effect on vascular endothelium and other tissues. The demonstration of the existance of protein-bound homocyst(e)ine has strengthened this hypothesis. In an attempt to remove bound homocyst(e)ine, mpenicillamine was given to three patients with pyridoxine-nonresponsive homocystinuria. Before the clinical trial, it had been demonstrated that 0.1 v o l e per ml concentration of ~penicillamine or cysteamine released approximately 50% of the homocyst(e)ine bound to plasma proteins in vitro. Oral mpenicillamine effectively reduced both free and plasma protein-bound homocyst(e)ine in homocystinurics from the second day of treatment. The homocystine excreted in the urine was mainly in the form of homocysteine-penicillamine disulfide. No mixed disulfide was detectable in the plasma, indicating an extremely high renal clearance. These observations suggested that oral wpenicillamine removed a considerable quantity of the bound homocyst(e)ine accumulated in the tissue proteins. Speculation D-Penicillamine treatment may be used on an experimental basis in pyridoxine-nonresponsive homocystinuric patients when dietary treatment is not practical. It may also be used in pyridoxine-responsive patients when control with pyridoxine is unsatisfactory. In addition, determination of protein-bound homocyst(e)ine should be used for the assessment of the effectiveness of therapy.Homocystinuria may be due to a metabolic block in the synthesis of cystathionine from homocysteine and serine, or due to defects in the remethylation of homocysteine to methionine, resulting in an accumulation of homocystine in the plasma and urine (1, 3, 8, 13-15, 17, 20); however, homocystine is not found in tissue fluids of normal subjects when conventional methods are used for detection.Recently, using a new method, we demonstrated the presence of protein-bound homocyst(e)ine in the plasma of both normal and homocystinuric subjects (10). Furthermore, we were able to demonstrate a significantly elevated concentration of proteinbound homocyst(e)ine (7-10-fold of normal value) in pyridoxine responsive patients when free homocystine was undetectable in the plasma. A large amount of protein-bound homocyst(e)ine was also demonstrated in the brain, liver and kidney of homocystinuric patients. These observations might account for the findings that some clinical abnormalities such as ectopia lentis and abnormal morphology in the hepatocytes persisted or developed in pyridoxine responsive homocystinuric patients despite the absence of free homocystine in their tissue fluids (4, 5, 7). We postulated that the formation of protein-bound homocyst(e)ine might be responsible for the direct damaging effect of homocystine on the vascular endothelium and other tissues. We therefore attempted to dissociate and remove protein-bound homocyst(e)ine.The studies in this paper provide evidence that oral D-penicillamine produces a significant reduction of free and plasma protein-bound homocyst(e)ine in patien...

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“…Dystonia in association with homocystinuria has been previously documented in 10 case reports; 5 of these cases were described in the absence of basal ganglia infarction, implicating a possible metabolic pathogenesis. These cases, however, were of childhood onset and were not relapsing 4–9. The recurrent nature of the dystonia in our patient is, as far as we are aware, unique and may provide a clue for the pathogenesis.…”

Section: Discussionmentioning

confidence: 58%

Recurrent dystonia in homocystinuria: A metabolic pathogenesis

2006

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Dystonia complicating homocystinuria is extremely rare in the absence of thromboembolic disease. We report a unique case of recurrent dystonia in a patient with homocystinuria secondary to pyridoxine-unresponsive cystathionine beta-synthase deficiency. Brain MRI was normal. Two biochemical markers for homocystinuria, homocystine and methionine, were markedly elevated during periods when our patient manifested dystonia. These findings suggest that accumulation of sulfur-containing amino acids may contribute to the pathophysiology of dystonia in patients with homocystinuria.

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A Case of Homocystinuria with a Dystonic Neurological Syndrome

Cited by 21 publications

References 1 publication

Homocystinuria Treated With Pyridoxine

Homocystinuria Treated With Pyridoxine

The Effect of D-Penicillamine on Protein-Bound Homocyst(e)ine in Homocystinurics

Recurrent dystonia in homocystinuria: A metabolic pathogenesis

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