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The geniuses Robert Schumann and Vincent Van Gogh show striking similarities both in the longitudinal nature of the progression of their illnesses, and the symptoms they experienced. There have been physiological explanations posed for both men, including Meniere's disease, tertiary syphilis, acute intermittent porphyria, terpenoid and lead poisoning, intracranial masses, temporal lobe epilepsy and dementia caused by vascular hypertension. The evidence for these physiological explanations is assessed. Schizophrenia and Bipolar disorder have also both been postulated to explain the symptoms of the two men, but neither man perfectly fits the diagnostic criteria for either. Schizoaffective disorder is a term used to describe patients who experience symptoms from both the psychosis of Schizophrenia and the mood disorders of Bipolar disorder. This paper aims to explain why Schizoaffective disorder explains the symptomology of these men better than either Schizophrenia or Bipolar disorder does alone. Schizoaffective disorder, however, did not exist as a diagnosis when Van Gogh and Schumann were alive, and so was not considered by their physicians.
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PMID:Does Schizoaffective Disorder explain the mental illnesses of Robert Schumann and Vincent Van Gogh? 3043 46

Acute intermittent porphyria (AIP), an autosomal dominant inborn error of metabolism, is the most common and severe form of the acute porphyrias. Attacks of severe abdominal pain, often with hypertension, tachycardia, are cardinal features of AIP, often requiring hospital admissions. Frequent recurrent attacks of AIP, defined as >3 attacks in one year, during which at least one attack requires intravenous heme therapy, are associated with significant morbidity, lost productivity, and health care burden. We report two patients with such frequent attacks of AIP, who have been managed with prophylactic heme therapy on a weekly basis. We describe results particularly in relation to symptom control, biochemical findings, health care costs, quality of life, and utilization of resources. During 11-month duration of weekly prophylactic heme infusions, we observed a 100% decrease in acute attacks and inpatient admissions in one subject and a 75% decrease in the other. During this time, we also observed a significant decrease in the number of emergency room visits. The decrease in number of acute attacks requiring hospital admission was associated with significantly decreased health care costs and improved quality of life. Reduction of both emergency room visits and hospital admissions decreased the utilization of health care services. Outpatient weekly infusions were also noted to be associated with better reimbursements and reduced overall costs of health care for the subjects. Both our subjects also endorsed better symptom control, quality of life and better understanding of disease. Thus, prophylactic heme therapy, through a multi-disciplinary approach, decreases the incidence of acute attacks, decreases health care costs and leads to better patient satisfaction and quality of life.
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PMID:Benefits of prophylactic heme therapy in severe acute intermittent porphyria. 3073 21

The acute hepatic porphyrias include four disorders: acute intermittent porphyria [AIP], hereditary coproporphyria [HCP], variegate porphyria [VP], and the rare porphyria due to severe deficiency of ALA dehydratase [ADP]. In the USA, AIP is the most severe and most often symptomatic. AIP, HCP, and VP are due to autosomal dominant genetic abnormalities, in which missense, nonsense, or other mutations of genes of normal hepatic heme biosynthesis, in concert with other environmental, nutritional, hormonal and genetic factors, may lead to a critical deficiency of heme, the end-product of the pathway, in a small but critical 'regulatory pool' within hepatocytes. This deficiency leads to de-repression of the first and normally rate-controlling enzyme of the heme synthetic pathway, delta- or 5-aminolevulinic acid [ALA] synthase-1, and thus to marked up-regulation of this key enzyme and to marked hepatic overproduction of ALA. In addition, except for ADP, there is marked overproduction as well of porphobilinogen [PBG], the intermediate immediately downstream of ALA in the synthetic chain, and, especially in HCP and VP, also porphyrinogens and porphyrins farther down the pathway. The major clinical features of the acute porphyrias are attacks of severe neuropathic-type pain. Pain is felt first and foremost in the abdomen but may also occur in the back, chest, and extremities. Attacks are more common in women than in men [ratio of about 4:1], often accompanied by nausea, vomiting, constipation, tachycardia, and arterial hypertension. Hyponatremia may also occur. Some patients also describe chronic symptoms of pain, anxiety, insomnia, and others.
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PMID:Pathogenesis and clinical features of the acute hepatic porphyrias (AHPs). 3098 16

Acute intermittent porphyria (AIP) is rare and the diagnosis is often delayed. It usually presents with abdominal symptoms, behavioural changes, seizures, tachycardia, and hypertension. MRI findings are usually normal or few contrast enhancing lesions may be present. Rarely , reversible vasogenic edema is seen on MRI as T2 weighted and FLAIR hyper intensity without diffusion restriction suggestive of posterior reversible encephalopathy syndrome (PRES). Review of literature suggests that there are only few case reports of AIP associated with PRES. Because diffusion-weighted MRI is normal, the lesions are likely caused by reversible vasogenic edema and transient breakdown of the blood-brain barrier. Treatment of porphyria consists of a high carbohydrate diet supplemented with the use of intravenous glucose and haematin infusions during acute attacks. Management of seizures with commonly used anti-epileptics including phenytoin, valproic acid, carbamazepine and barbiturates can worsen symptoms or precipitate acute attacks because of their enzyme inducing activity. Levetiracetam is the preferred choice these cases. Porphyria is an important differential diagnosis in patients with unexplained abdominal pain along with neuro-psychiatric manifestations. This case report adds to a handful of cases worldwide associating AIP with radiological findings of PRES.
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PMID:Porphyria: An Uncommon Cause of Posterior Reversible Encephalopathy Syndrome. 3164 73

Mutations in hydroxymethylbilane synthase (HMBS) cause acute intermittent porphyria (AIP), an autosomal dominant disease where typically only one HMBS allele is mutated. In AIP, the accumulation of porphyrin precursors triggers life-threatening neurovisceral attacks and at long-term, entails an increased risk of hepatocellular carcinoma, kidney failure, and hypertension. Today, the only cure is liver transplantation, and a need for effective mechanism-based therapies, such as pharmacological chaperones, is prevailing. These are small molecules that specifically stabilize a target protein. They may be developed into an oral treatment, which could work curatively during acute attacks, but also prophylactically in asymptomatic HMBS mutant carriers. With the use of a 10,000 compound library, we identified four binders that further increased the initially very high thermal stability of wild-type HMBS and protected the enzyme from trypsin digestion. The best hit and a selected analog increased steady-state levels and total HMBS activity in human hepatoma cells overexpressing HMBS, and in an Hmbs-deficient mouse model with a low-expressed wild-type-like allele, compared to untreated controls. Moreover, the concentration of porphyrin precursors decreased in liver of mice treated with the best hit. Our findings demonstrate the great potential of these hits for the development of a pharmacological chaperone-based corrective treatment of AIP by enhancing wild-type HMBS function independently of the patients' specific mutation.
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PMID:A Pharmacological Chaperone Therapy for Acute Intermittent Porphyria. 3181 Aug 63


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