El síndrome del cerebro descalificado: redivivo / The disquality brain syndrome: revivified

Se describe una nueva patología nostra-de nosotros los médicos-un nuevo síndrome que afecta al médico moderno en su relación con sus pacientes y enfermedades. Se postula que el ente mórbido toma su origen en la servil sumisión del facultativo ante la ¨Deidad Máquina¨ a quien concede, entre otros atributos, omnisciencia y omnipotencia. Como resultado de su fantasía, con mucha frecuencia ¨descalifica su cerebro¨ y abdica su juicio clínico a favor de los dictados erróneos de aquella, con el consiguiente perjuicio para el paciente. Como ilustración de la condición se narran las vicisitudes de algunos enfermos y el tortuoso camino del diagnóstico de sus condiciones patológicas

The ¨dysqualified¨ brain syndrome. The author describes a hitherto undescribed syndrome which affects the modern physician and his/her relationship with patients and their diseases. He postulates that the morbid entity takes its origin from the doctor’s submission to the ¨Machine Deity¨ to whom he concedes, among other attributes, those of omnipotence and omniscience. As a result of this fantasy, physicians frequently ¨disqualify¨ his/her brain,and abdicate their clinical judgment in its favor with the ensuing disservice to their patients. As an illustration of such condition, the difficulties of several patients are presented, whose diagnostics were abusive, erroneous or delayed due to deficient clinical histories

Mutations in phosphoinositide metabolizing enzymes and human disease.

Phosphoinositides are implicated in the regulation of a wide variety of cellular functions. Their importance in cellular and organismal physiology is underscored by the growing number of human diseases linked to perturbation of kinases and phosphatases that catalyze interconversion from one phosphoinositide to another. Many such enzymes are attractive targets for therapeutic interventions. Here, we review diseases linked to inheritable or somatic mutations of these enzymes.

Lowe syndrome.

Lowe syndrome (the oculocerebrorenal syndrome of Lowe, OCRL) is a multisystem disorder characterised by anomalies affecting the eye, the nervous system and the kidney. It is a uncommon, panethnic, X-linked disease, with estimated prevalence in the general population of approximately 1 in 500,000. Bilateral cataract and severe hypotonia are present at birth. In the subsequent weeks or months, a proximal renal tubulopathy (Fanconi-type) becomes evident and the ocular picture may be complicated by glaucoma and cheloids. Psychomotor retardation is evident in childhood, while behavioural problems prevail and renal complications arise in adolescence. The mutation of the gene OCRL1 localized at Xq26.1, coding for the enzyme phosphatidylinositol (4,5) bisphosphate 5 phosphatase, PtdIns (4,5)P2, in the trans-Golgi network is responsible for the disease. Both enzymatic and molecular testing are available for confirmation of the diagnosis and for prenatal detection of the disease. The treatment includes: cataract extraction, glaucoma control, physical and speech therapy, use of drugs to address behavioural problems, and correction of the tubular acidosis and the bone disease with the use of bicarbonate, phosphate, potassium and water. Life span rarely exceeds 40 years.

[Recent progress in molecular biology of inherited tubular transport abnormalities].

Recent progress in the molecular biological approach to analysis of inherited tubular transport abnormalities is reviewed. 1) cDNAs of several mammalian proteins, related to amino acid transport in renal tubular cell, have been cloned using an expression cloning in Xenopus oocytes. One of them stimulates the transport of cystine, dibasic amino acids and neutral amino acids and will accelerate the analysis of cystinuria. 2) Isolation of cDNAs, encoding human and rat vasopressin V2 receptors, has been reported. The deduced amino acid sequence seems to be a member of receptors with seven putative transmembrane regions. Analysis of this gene from patients with nephrogenic diabetes insipidus is in progress. 3) Analysis of carbonic anhydrase II (CA II) gene in a Belgian family with renal tubular acidosis associated with osteoporosis and cerebral calcification has shown a point mutation replacing an invariant histidine residue of CA II protein with tyrosine. 4) Oculocerebrorenal syndrome of Lowe (OCRL) is a X-linked disorder affecting the lens, brain and kidneys. The OCRL locus has been mapped to Xq24-26 by linkage analysis and by finding de novo X-autosome translocations at Xq24-26 in two unrelated females with OCRL. A cDNA has been isolated using yeast artificial chromosome and DNA inserts that span the X chromosome breakpoint from a female patient. Transcript for this cDNA is absent in unrelated male patients. The open reading frame encodes a new protein similar to human inositol-polyphosphate-5-phosphatase, raising a possibility that OCRL is an inborn error of inositol phosphate metabolism.