R. W. E. Watts's research while affiliated with Ealing, Hammersmith & West London College and other places
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Publications (224)
The decision to treat a patient with primary hyperoxaluria type 1 (PHI) by combined liver and kidney transplantation, the former to correct the metabolic lesion which was then thought to be deficiency of cytoplasmic 2-oxoglutarate:glyoxylate carboligase, and the latter to replace the organ which is destroyed, provided an opportunity to investigate...
Two patients with Type 1 (adult) Gaucher's disease and major skeletal involvement with multiple fractures have been treated with the second generation bisphosphonate pamidronate for extensive periods. There was evidence of an immediate reduction in bone resorption, with increased calcium absorption (delayed in Patient 1), improved calcium balance a...
Complete hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency causes the Lesch-Nyhan syndrome, an X-linked, purine metabolism disorder manifested by hyperuricemia, hyperuricaciduria, and neurologic dysfunction. Partial HPRT deficiency causes hyperuricemia and gout. One requirement for understanding the molecular basis of HPRT deficiency...
Purpose and patients and methods:
The purpose of this article is to report the experience of three centers with combined hepatic and renal transplantation for pyridoxine-resistant primary hyperoxaluria type I (alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency), with particular emphasis on the selection criteria and timing of the operati...
We report on a family with a sibship of three children for whom the diagnosis of "an unusual form of metachromatic leukodystrophy (MLD)" had been suggested earlier. The patients had choreiform movements and dystonic posturing accompanied by dysarthria since childhood. The availability of the polymerase chain reaction enabled us to show that the thr...
The following main conclusions concerning the transplantation strategies to be adopted in primary hyperoxaluria type 1 (PH1) were drawn from the data collected from 22 patients who received combined liver-kidney grafts and 2 patients who received isolated liver grafts in Europe from June 1984 to March 1990. In end-stage renal failure due to PH1 liv...
The data provided by 14 European centres concerning 22 combined liver-kidney and two isolated liver grafts performed in primary hyperoxaluria type 1 (PH1) were discussed at a workshop which drew the following main conclusions: 1. In end-stage renal failure due to PH1 1-year kidney graft survival rate is far better after combined liver-kidney transp...
The data provided by 14 European centres concerning 22 combined liver-kidney and two isolated liver grafts performed in primary hyperoxaluria type 1 (PH1) were discussed at a workshop which drew the following main conclusions:
1. In end-stage renal failure due to PH1 1-year kidney graft survival rate is far better after combined liver-kidney transp...
Animal and in vitro studies have implicated decreased protein synthesis in the pathogenesis of tissue damage in phenylketonuria (PKU) and of growth failure in Lesch-Nyhan syndrome. Protein turnover was measured in vivo in ten young adult subjects with classical PKU, two subjects with hyperphenylalaninemia, and three children with Lesch-Nyhan syndro...
Extreme degrees of hypoxanthine phosphoribosyltransferase (HPRT) deficiency in man are associated with gross sex-linked neurological dysfunction, gout and urinary stones (the Lesch-Nyhan or 'complete HPRT-deficiency' syndrome). The less severe degrees of enzyme deficiency (sex-linked recessive gout and/or urolithiasis or the 'partial HPRT-deficienc...
Urinary stone formation depends on the degree of saturation of the urine with respect to potential stone-forming substances. Urine contains a range of electrolytes which ionise to different and variable degrees and which interact with one another in ways which influence their solubilities. These ionisations are themselves influenced by the pH of th...
In normal adults the urinary excretion of oxalate rarely exceeds 0.5 mmol/24 hours-1 despite dietary and seasonal fluctuations of intake and absorption. Hyperoxaluria may be encountered in a number of disease states because of increased absorption of dietary oxalate or derangements of metabolism (Table 1). More unusually, hyperoxaluria may arise fr...
Purine metabolism in the Lesch-Nyhan syndrome has been re-examined in 10 patients. Hypoxanthine and xanthine concentrations in plasma and CSF and urinary excretion have been studied, on and off allopurinol treatment, using high performance liquid chromatographic methods. Accumulation of the substrate, hypoxanthine, of the missing hypoxanthine guani...
Oxalate metabolism was studied in ten patients with end-stage renal disease. No patient with primary hyperoxaluria was included in this study. Five patients were on regular haemodialysis and five patients were on chronic ambulatory peritoneal dialysis (CAPD). Oxalate metabolism was assessed by measurement of plasma oxa late concentration (Pox) oxal...
The primary hyperoxalurias comprise three inborn errors of metabolism in which the urinary oxalate excretion is abnormally high (Table 5.1). Increases in the urinary oxalate excretion due to dietary and seasonal fluctuations in the intake and absorption of oxalate rarely cause the excretion of more than 0.5 mmol/24 h in adults. The three types of p...
Primary hyperoxaluria is a rare inherited metabolic disease in which striking oxalate overproduction is associated with recurrent calcium oxalate urolithiasis leading to end-stage renal failure before the end of the second or third decade. Because conventional methods of renal substitution such as regular dialysis or renal transplantation do not al...
A patient with primary hyperoxaluria type 1 (hepatic peroxisomal alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency) was successfully treated by combined hepatic and renal transplantation. The metabolic lesion was corrected by replacement of the deficient hepatic enzyme activity.
The increased production and excretion of oxalate in primary hyperoxaluria causes urolithiasis, nephrocalcinosis with renal failure, and systemic oxalosis. Systemic oxalosis occurs late in the course of the disease when there is both oxalate retention and increased oxalate synthesis. The uraemia can be controlled by conventional haemodialysis or pe...
A deficiency of activity of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT,EC 2.6.1.44)has been found in the livers of six patients with primary hyperoxaluria type 1 (PH), including three in whom the tissue was obtained by percutaneous needle biopsy. AGT activity, assayed in unfractionated liver tissue, ranged from 11 to 47% of the...
In order to separate the effect of oxalate retention in primary hyperoxaluria with renal failure from that of excessive oxalate synthesis and to determine the optimum time for renal transplantation in primary hyperoxaluria, we have studied a series of patients with different degrees of renal failure due to other causes. The results were compared wi...
There is a failure of growth in hypoxanthine guanine phosphoribosyltransferase deficiency; slow weight gain is marked after the second year of age but is apparent in the birth weights of all eight of our patients for whom we have data. However, head growth and bone development are less affected than weight.
A partial defect in the adrenocortical 11...
In order to separate the effect of oxalate retention in primary hyperoxaluria with renal failure from that of excessive oxalate synthesis and to determine the optimum time for renal transplantation in primary hyperoxaluria, we have studied a series of patients with different degrees of renal failure due to other causes. The results were compared wi...
1. The subcellular distribution of 2-oxoglutarate:glyoxylate carboligase was investigated in a normal human liver, a liver from a patient with pyridoxine-resistant primary hyperoxaluria type I and rat livers subjected to various degrees and types of trauma.
2. On continuous sucrose gradients most of the carboligase fractionated with a peak equilibr...
We report studies on two patients (1 and 2) with Hurler disease. They both had all of the non-neurological features of Hurler disease to a similar and extreme degree and similar signs of brain damage on computed tomography. However, intellectual function was unusually well-preserved in patient 1, but seriously and typically impaired in patient 2. T...
We have investigated the usefulness of a full-length cDNA probe for the hypoxanthine phosphoribosyltransferase, HPRT gene in the diagnosis of the carrier state for the Lesch-Nyhan syndrome in 13 families. The products of DNA digestion by 21 different restriction enzymes were examined by Southern analysis. The only useful polymorphism detected was a...
The overall activity of the purine de novo synthesis pathway and the activities of purine phosphoribosyltransferase in the rat testis were measured at different ages and were correlated with histological observations. Similar studies of the concentration of circulating gonadotrophins and testosterone were performed. The purine phosphoribosyltransfe...
A case is reported of a patient with renal failure and developing systemic and renal oxalosis due to pyridoxine-resistant type I primary hyperoxaluria. In spite of vigorous haemodialysis and hydration before and after operation, an allografted cadaveric kidney failed because of oxalate deposits in the transplant.
The patient was treated by combined...
1. We have measured glomerular filtration rate (GFR), extracellular fluid volume (ECF), oxalate distribution volume (OxDV), plasma oxalate concentration (POx.), plasma total clearance of oxalate (PCOx.), oxalate metabolic pool size [(OxDV) × (POx.)], renal clearance of oxalate (RCOx.), oxalate excretion, tissue clearance of oxalate (TCOx.) and tiss...
The structural basis of the combined conductive and sensorineural deafness has been described in two patients with Hurler's disease. All parts of the ear contained numerous large vacuolated Hurler cells, the vacuoles being distended lysosomes from which accumulated glycosaminoglycans had been dissolved during fixation of the tissue. The external an...
The metabolic pathways of pterin de novo synthesis, interconversion and salvage which lead to the tetrahydrobiopterin cofactor of phenylalanine 4-monooxygenase, tyrosine 2-monooxygenase and tryptophan 5-monooxygenase are reviewed and data on the enzymes which catalyze the individual steps are presented. Analogies drawn between the inborn errors of...
1. We have measured the rate of purine synthesis de novo in blood mononuclear cells in vitro and the activities of the purine salvage enzymes [hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8), adenine phosphoribosyltransferase (APRT; EC 2.4.2.7)] and ribosephosphate pyrophosphokinase (PP-ribose-P synthetase;EC 2.7.6.1)] and the concentrati...
1. We have measured the plasma oxalate concentration (POx), urinary oxalate excretion (UOx), oxalate equilibrium distribution volume (ODV), oxalate metabolic pool size [(ODV) × (POx)], total plasma oxalate clearance (PCOx), renal (or dialyser) oxalate clearance (RCOx), non-renal oxalate clearance (NRCOx) and the tissue oxalate accretion rate (TOA)=...
Previous work in which we measured the specific activities of amidophosphoribosyltransferase (PRPP-At; EC 2.4.2.14) and hypo-xanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8) in the brains of rats at different ages suggested that the HPRT-catalysed purine salvage pathway became more important relative to the purine de novo synthesis pathway aft...
Using an in vitro method, the uptake of radio-labelled Ca2+ by jejunal biopsy specimens from control subjects, patients with idiopathic hypercalciuria and patients with renal stones without hypercalciuria, were compared. Radio-labelled Ca2+ uptake was investigated over the concentration range 0.1-5.0 mmol/l. For all subjects there was a linear rela...
1. We have measured the total plasma clearance, renal clearance and equilibrium distribution volume of [14C]oxalate, and the urinary oxalate excretion rate and plasma oxalate levels at approximately 6 month intervals for up to 2.5 years in five patients with primary hyperoxaluria. The renal clearance and distribution volumes of [99mTc]DTPA (diethyl...
This communication reports studies on the composition of the urinary glycosaminoglycans and oligosaccharides in mucopolysaccharidosis patients who were being treated by fibroblast transplantation. The urinary glycosaminoglycans were precipitated with 9-aminoacridine, the oligosaccharides remaining in solution. Both fractions were further subfractio...
Biochemical and pathological observations on tissues from two patients with Hurler disease (mucopolysaccharidosis IH; alpha-L-iduronidase deficiency) who had been treated by fibroblast transplants as a means of enzyme replacement treatment are reported. These results and those obtained in three surgical specimens [ligamentum flavum with dura mater...
The aim of this study was to try to elucidate the increased susceptibility of the neck of femur to fracture. Quantitative polarised light microscopy has been applied to fresh, undecalcified sections of samples of bone taken from the site of fracture, in specimens taken at operation from patients with fractures of the femoral neck or osteoarthritic...
This paper reports the clinical and biochemical results in six patients with Hurler disease (Mucopolysaccharidosis IH; McKusick 25280), two patients with Hunter disease (Mucopolysaccharidosis II; McKusick 25285) and one patient with Sanfilippo B disease (Mucopolysaccharidosis IIIB; McKusick 25292) who were treated by fibroblast transplantation. Exc...
The regulation and integration of purine nucleotide biosynthesis is considered from the viewpoint of the main groups of reaction sequences involved and with respect to some specific organs and tissues. Inhibiting either IMP dehydrogenase or adenylosuccinate synthetase in rat liver in vitro reduced the rate of purine do novo synthesis with respect t...
The rate of purine de novo synthesis from sodium formate in developing rat brain falls in the late gestational stages to birth, rises again in the 1st week of life and then decreases rapidly to the 3rd week, and continues declining up to 8 weeks of life (adulthood). The changes in the overall purine biosynthetic rate with respect to time are simila...
Normal serum concentrations of methionine, leucine, isoleucine and valine have been found in 10 anaesthetists using nitrous
oxide under their regular working conditions without scavenging of patients' exhaled gas. Mean inhaled concentrations of nitrous
oxide ranged from 150 to 400 p.p.m. The results indicate either that there was no significant inh...
This paper reports our 10 years experience in the management of patients with the Lesch-Nyhan syndrome. It is based on the detailed study of eight patients, the longest period of follow-up being about eight years. The usual clinical descriptions have emphasized spasticity with pyramidal tract signs, choreoathetosis, compulsive self-injurious behavi...
We have studied purine metabolism in mononuclear and polymorphonuclear cells from uraemic patients using microradiochemical enzyme assays and high-pressure liquid chromatography. In mononuclear cell lysates the mean activities of adenosine deaminase (EC 3.5.4.4) and 5'-nucleotidase (EC 3.1.3.5) were significantly diminished. The activities of adeny...
1. We have studied purine metabolism in renal failure using high-pressure liquid chromatography to determine metabolite concentrations in erythrocytes and plasma, and microradiochemical assays of enzyme activity in erythrocytes.
2. the mean activities of some of the enzymes involved in purine metabolism were raised in renal failure. Significant ele...
The appearances on computed tomography (CT) in eight patients with mucopolysaccharidosis Type I [five with classical Type IH (Hurler disease)], two with mucopolysaccharidosis Type II (Hunter disease) and two with mucopolysaccharidosis Type IIIB (Sanfilippo B disease) are presented. Reference is also made to two further cases [mucopolysaccharidosis...
urinary organic acid metabolite excretion patterns in normal newborns aged 1 to 7 days were analysed by GC and MS. Statistical analysis showed significantly different relationships between metabolite excretion, age, sex and feed. The data provide a necessary background for the diagnosis of inborn errors or organic acid metabolism.
Siblings (one male and one female) with a striking combination of multiple skeletal abnormalities, hypermobility in some joints with a restricted range of movements in others, mesodermal dysgenesis of the iris and cutaneous atrophy with thin skin, multiple telangiectases, shallow ulcers, and café au lait lesions are described. The patients were rep...
In order to evaluate the contribution of patients with organic aciduria and amino acidopathies to populations with severe long-term mental handicap, urine from a total of 1,778 such patients from four hospitals has been examined for organic acids and amino acids. The patients have been classified into eight groups according to the nature of their h...
In-vitro calcium influx was measured in jejunal biopsy specimens from 10 men with idiopathic hypercalciuria. Calcium uptake in these adults was a passive process which was not sensitive to inhibition by 2,4 dinitrophenol and sodium fluoride, and showed no evidence of carrier saturation. In 7 of 10 patients with idiopathic hypercalciuria calcium upt...
The electron microscopic appearances of the corneoscleral and iris tissue removed at operation from a child with Hurler disease and glaucoma showed distinctive swollen cells with intracellular inclusions similar to those which are observed in other tissues in these patients and which are due to abnormal lysosomal storages of mucopolysaccharides. So...
The association of retroperitoneal fibrosis and systemic sclerosis is reported from a patient positive for the HLA-B27 antigen. This appears to be the first report of such an association. Pathological features common to the 2 syndromes are discussed and the literature is reviewed.
(1) This communication reports the amidophosphoribosyltransferase (PRPP-At; EC 2.4.2.14), hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.7) and adenine phosphoribosyltransferase (APRT; EC 2.4.2.8) activities and the phosphoribosylpyrophosphate (PRPP) content of rat brain at different stages of development. The results are not age-related in...
The discovery that the metabolic lesion in Hurler disease fibroblasts could be corrected by growing the cells in tissue culture medium in which non-Hurler disease fibroblasts had grown, the cross-correction phenomenon, and later work on the release and reuptake of lysosomal hydrolases, and of α-iduronidase in particular, by fibroblasts in vitro sup...
This investigation was undertaken in order to define the place of multidisease screening for inborn errors of metabolism in paediatric practice with particular reference to the organic acidurias, and to compare the efficiency of organic acid screening as a detection method for inborn errors of metabolism with that of amino acid screening on urine....
We describe the case of an otherwise healthy 7-year-old girl whose mother noticed that she intermittently smelt of fish. This was due to the intermittent excretion of trimethylamine which could be precipitated by choline ingestion and by eating fish. Excluding eggs, liver and salt-water fish from the diet relieved the symptom. After a standard 15 g...
A patient with protein-losing gastroenteropathy and egg allergy has been shown to have a previously unrecognized organic aciduria, D-2-hydroxyglutaric aciduria. The observations made are consistent with an inherited metabolic disorder in the catabolism of 5-aminolaevulinate possibly due to deficient activity of a specific D-2-hydroxyglutarate dehyd...
The availability of purine nucleotides at their sites of physiological action depends upon the balance between purine synthesis de novo and the purine phosphoribosyltransferase catalysed purcine salvage reactions. It was reported that purine synthesis de novo was considerably less active in brain tissue than in liver1.
The organic acidurias may be broadly defined as those inborn errors of metabolism in which the specific inherited metabolic lesion causes an abnormal excretion of a non-amino carboxylic acid. The characteristic excretion product may contain other functional groups (e.g., oxo- or hydroxy-) and may be either aliphatic or aromatic. Taken in this broad...
The results are described of a behavioural programme designed to modify self‐injurious behaviour of a child with Lesch‐Nyhan syndrome. The treatment combined extinction of the injurious behaviour and reinforcement of alternative behaviour, and was successful in the controlled hospital environment. However, an attempt to teach the parents to continu...
This chapter discusses a study to determine whether the subcutaneous implantation of histocompatible fibroblasts corrects the biochemical lesion in Hurler's disease and modifies the clinical course of the disease. In the study, the biochemical effect was monitored by changes in the urinary excretion of glycosaminoglycans (GAG) and by enzyme measure...
We report a family (parents and two sets of twin girls) in which the propositus presented as a case of phenylketonuria with a somewhat less severe degree of phenylalanine intolerance than occurs in patients with classical phenylketonuria and whose phenylalanine tolerance was further impaired by giving cotrimoxazole. The trimethoprim component of co...
Hyperuricaemia in Down's syndrome is unreleated to the activity of phosphoribosylamidotransfrease, which catalyses the activity of the first specific step on the purine biosynthetic pathway, and to the activity of hypoxanthine phosphoribosyltransferase and phosphoribosylpyrophosphate synthetase, abnormalities of which are known to be associated wit...
The effects of some putative inhibitors of oxalate production or urinary oxalate excretion have been investigated in the Cynamolgus monkey and in patients with Type I primary hyperoxaluria (hyperoxaluria with glycollic aciduria). Sodium-1-hydroxybutan-sulphonate, D,L-phenyllactate, succinimide and isocarboxazide did not reduce the urinary oxalate e...
The Lesch-Nyhan syndrome is an inheritable disease associated with a specific biochemical deficiency, and which manifests itself particularly in the form of motor disorders. In this article Dr. Watts describes the biochemical lesion, and, through the understanding of the biochemistry, has been able to make some intriguing suggestions as to the role...
The method for screening urinary oligosaccharides described in the accompanying paper [Clin. Chem. 24, 669 (1978)] has been applied to a large group of mentally handicapped patients as well as to patients with cystic fibrosis, malignant disease, and schizophrenia. The cause of the mental handicap was unknown in most cases. The primary object of the...
A method for screening urine for abnormalities in glycoconjugate excretion is presented. An oligosaccharide-containing fraction is isolated from urine by gel chromatography and the carbohydrate-containing components in this fraction are degraded to monosaccharides, suitable derivatives of which are analyzed by gas-liquid chromatography. A pattern w...
The previous report of low levels of purine 5'-nucleotidase activity in peripheral blood mononuclear cells (lymphocytes and monocytes) from patients with non-familial adult onset 'variable' primary hypogammaglobulinaemia has been confirmed and the observation extended to include patients with other types of primary immunodeficiency. Patients with s...
The inborn errors of metabolism are a series of individually rare biochemical anomalies some of which cause serious clinical manifestations. They are of great interest to biochemists and geneticists, as well as to paediatricians and internist for whom they often present special diagnostic and therapeutic problems. The study of the inborn errors of...
Biochemical and clinical studies on a patient with hepatic glycogen storage disease are reported. The patient showed many of the clinical and biochemical features of type I glycogenosis (glucose-6-phosphatase deficiency), but had normal activities of the following enzymes in liver tissue: glucose-6-phosphatase (EC3.1.3.9); amylo-1,6-glucosidase (EC...
Citations
... Indeed, the dependence of erythrocytes on HGprt-mediated salvage of hypoxanthine supplied into the circulation by the liver 74 may explain why macrocytic anemia is so common in LND 9,45 . Similarly, de novo purine synthesis seems to contribute to cell division and neurogenesis in the developing brain 56,75-77 , but the mature brain depends more on purine salvage 55,56,78 . Within the brain, neurons seem to express much more HGprt than glia 79 . ...
... Primary hyperoxaluria is a rare inborn error of metabolism involving oxalate by two distinct pathways: the more common type I primary hyperoxaluria has now been recognized to be due to deficiency of peroxisomal alanine:glyoxylate aminotransferase which is located in the liver cells [1]; the more rare type II is due to lack of D-glyceric dehydrogenase [2]. Both types are featured by a marked increase in oxalate endogenous production, which lead to progressive kidney destruction and to systemic tissue deposition of oxalate. ...
... The effects of smaller replacement doses have not been determined. Pharmacological doses of pyridoxine decrease plasma oxalate both in primary oxalosis (31) and in end-stage renal failure from other causes (32,33), possibly by increasing conversion of glyoxylate (the direct metabolic precursor of oxalate) to glycine, al-though experimental work suggests an effect on intestinal absorption of oxalate (34). The effect of subclinical pyridoxine deficiency or of physiological replacement doses on plasma oxalate in dialysis patients is unknown. ...
Reference: The Clinical Significance of Hyperoxalaemia
... L'activité de cette enzyme a été mesurée dans les érythrocytes et les cellules de peau (fibroblastes) mais aussi dans les cellules amniotiques des malades ). (McCreanor et al., 1987 ;Fairbanks et al., 2002). La production moindre de ces nucléotides entraînerait un rétrocontrôle positif sur la PRPPS, suractivant la voie de synthèse de novo pour compenser le manque de nucléotides, et donc augmentant la production d'IMP dégradé sous forme d'hypoxanthine puis d'acide urique ( Figure 10). ...
... There has long been concern regarding the accumulation and deposition of oxalate with an increased intake of vitamin C, as oxalate is a breakdown product of vitamin C and is heavily excreted by the kidneys [30]. Oxalate crystallization occurs at >30 mM [31] and high plasma oxalate levels occur in hemodialysis patients [32][33][34]. A recent prospective case series exploring high-dose intravenous vitamin C (15-100 g) administration reported that increased vitamin C intake was not associated with any cases of symptomatic renal stones and kidney injury [35]. ...
... In GSD-IA the urinary lactate excretion appeared to be a useful parameter to estimate the glucose requirement of the patient (2). 2-Oxoglutaric aciduria has been found incidentally in patients with enzyme defects of both the 2oxoglutarate dehydrogenase complex and the pyruvate dehydrogenase complex (3)(4)(5) and in one patient with GSD-IA and one patient with GSD-IB (6). Urinary citrate excretion has been studied in various inborn errors of metabolism with inconclusive results (6,7). ...
... The adrenal medulla may be directly affected by the absence of HPRT enzyme. Polyendocrinopathy is typical of this condition and has been previously documented (64). The deficiency of the normally high activities of HPRT in the testes appears to inhibit their ability to respond to gonadotrophin (64). ...
... We included 51 observational studies (see Fig. 1 for the study selection procedure). We found nine registry studies [4,[15][16][17][18][19][20][21][22], 35 single-centre studies [8,, two multicentre studies [57,58] and five studies using questionnaires [9,[59][60][61][62]. The studies were published between 1975 and 2020, and the number of included PH1 patients ranged from four to 201 (median 8, IQR 5-24). ...
... For patients with PH1, pyridoxine remains the only pharmacological treatment [5][6][7][8] although other options are currently being investigated [8][9][10][11][12]. Despite having been used for decades in PH1, there are still many questions regarding the effect of pyridoxine in PH1. ...
... To the best of our knowledge, however, this is the first report about the effect of AE on the salivary UA concentration of DS individuals. It is well known that serum UA is higher in DS patients than in healthy controls (Becker 1993;Peeters et al. 1993;Watts et al. 1979;Žitnanová et al. 2004). It has been hypothesized that UA could participate in the scavenging of free radicals and act as a biomarker of OS in DS patients (Žitnanová et al. 2004). ...
