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Biomedical subjects

G G Gascon

Publications and source records attributed to G G Gascon.

At least 19 recordsLinked to original sources
PubMed1996

Subacute sclerosing panencephalitis: evaluation with CT and MR.

PURPOSE: To evaluate the progression of CT and MR changes of the brain in subacute sclerosing panencephalitis (SSPE) as a basis for assessing the effects of different types of therapy. METHODS: Fifty-two patients with SSPE were examined, 44 with MR imaging and 42 with CT of the brain on one or more occasions. A total of 92 MR and 67 CT studies were performed. RESULTS: Correlation between the clinical status and the MR findings in admission was poor. Of 20 patients with clinically advanced disease, only 8 had marked MR abnormalities; 6 had normal or almost normal findings on MR examinations. Two of 4 patients with clinically mild disease had advanced MR changes. The progression of the MR findings appeared to follow a constant pattern. The earliest pathologic finding was focal, high-T2-intensity white matter changes; later atrophic changes followed. The atrophy lagged behind the white matter changes and was thus mild when white matter changes were moderate or severe. In the most advanced stage, when the patient was in a neurovegetative state, an almost total loss of white matter had usually taken place. At this stage, the corpus callosum was also thin. Basal ganglia changes, usually involving the putamina, were seen in one third of patients and cortical gray matter changes were seen in one fourth of patients examined with MR imaging. In 2 of 20 patients, MR changes regressed in parallel with clinical improvement following therapy, but in 5 patients clinical improvement was accompanied by progression of MR changes. CONCLUSION: The progress of MR abnormalities seen in patients with SSPE seems to follow a constant pattern, but the severity of MR changes does not always correlate well with the clinical findings. Caution must therefore be used when evaluating the effects of therapy.

Adolescent↗
PubMed1995

Familial childhood primary lateral sclerosis with associated gaze paresis.

Three children from consanguineous parents began losing the ability to walk in late infancy. Despite chronically progressive weakness leading to wheelchair dependence by adolescence and later loss of motor speech production, intellect remained preserved. Examination revealed upper motor neuron findings of pseudobulbar palsy and spastic quadriplegia, without dementia, cerebellar, extrapyramidal or sensory signs. In addition they exhibited a diffuse conjugate saccadic gaze paresis, especially severe on down-gaze. CT and MRI scans of brain and spinal cord, EEGs, visual and brainstem auditory evoked potentials, CSF examinations, enzyme assays for lysosomal storage diseases, blood amino acids and urine organic acids were all normal. Cortical somatosensory evoked potentials were poorly configured in two of the patients, though they had normal central conduction. EMG showed no signs of denervation. Nerve conduction studies showed normal peripheral motor and sensory conduction velocities. Transcranial magnetic stimulation of the brain elicited no motor-evoked potentials. Despite the lack of neuropathological confirmation, the clinical course and neurophysiologic data strongly support the diagnosis of a familial (autosomal recessive) primary lateral sclerosis (PLS).

Adolescent↗
PubMed1995

Ataxia-oculomotor apraxia syndrome.

Ataxia-oculomotor apraxia is a distinct entity first comprehensively described in 1988. The features include early childhood onset of ataxia and oculomotor apraxia, mimicking ataxia telangiectasia but without the extraneurologic findings of ataxia telangiectasia. We add to the clinical description of the ataxia-oculomotor apraxia syndrome by reporting eight patients, ages 2 to 15 years, from four families, suggesting autosomal recessive inheritance, with the longest follow-up over 6 years. After initial gait deterioration, all had a nonprogressive course. We have postulated that ataxia-oculomotor apraxia should be established as a separate disease from ataxia telangiectasia or its variants not only by clinical history, examination findings, and course, but primarily by the biologic markers of normal chromosome breakage and radiation sensitivity studies. We found no increased chromosome breakage in the four patients studied and intermediate sensitivity to chronic ionizing radiation of cultured skin fibroblasts on the three patients studied. Family studies revealed an intermediate radiosensitivity from two patients, their asymptomatic parents, and a sister. The lack of chromosome breakage strongly separates ataxia-oculomotor apraxia from ataxia telangiectasia. The radiation sensitivity studies are compatible with two possibilities: (1) symptomatic ataxia telangiectasia heterozygotes, but this would be highly unusual because the degree of clinical involvement in the ataxia-oculomotor apraxia patients is not mild, as would be expected if they were heterozygotes and (2) a separable disease entity, which is the interpretation we favor.

Adolescent↗
PubMed1994

Experience of King Faisal Specialist Hospital and Research Center with Saudi organic acid disorders.

The Inborn Errors of Metabolism and Neurology Services of the King Faisal Specialist Hospital and Research Centre (KFSH&RC) and Armed Forces Hospital have received more than 1,500 patients suspected of having an organic acid disorder (OAD) during a period of four years. Of these, 307 patients suspected of having an organic acid disorder (OAD) during a period of four years. Of these, 307 patients, approximately 20%, had a clearly identifiable disorder. Identified OAD's constituted one-quarter of all patients diagnosed as having various types of inborn errors of metabolism during this period, in these clinical services. Prolonged follow-up was available in the majority of cases, allowing detailed clinical, neuroradiologic and neurophysiologic descriptions. Fifty patients (16%) had rare disorders by standards in the West. Approximately 25% were 'neurologic organic acidurias.' This is a new term we are introducing for OAD's manifesting primarily with neurologic signs, but without appreciable acidosis, hypoglycemia or hyperammonemia. In this special issue, we present the KFSH&RC experience with the rare disorders as individual articles. We estimate the frequency of OAD's in Saudi Arabia as 1/740 births. The increased frequency of OAD's in Saudi Arabia is probably due to increased consanguinity, since most OAD's occurred in excess in certain tribes; and due to increased surveillance and testing by our group. Saudi Arabia provides a unique opportunity for research in this area of pediatrics.

Brain Diseases, Metabolic↗
PubMed1994

Ethylmalonic aciduria: an organic acidemia with CNS involvement and vasculopathy.

Five infants from 3 families, one Egyptian, two Yemeni, are described with a progressive encephalopathy, four of whom have been studied in detail. All patients showed vascular lesions of the skin, characterized by waxing and waning petechiae and ecchymoses. Acrocyanosis was present in three patients. All patients showed retinal lesions characterized by tortuous veins. Protracted diarrhea was not a consistent finding, although they had metabolic crisis in association with diarrhea. They did not show failure to thrive. The neurologic symptoms were indicative of a progressive pyramidal tract disease. Three patients died following sudden emergence of severe basal ganglia, putaminal and head of caudate lesions. In one patient the CT changes in brain were suggestive of infarction. The patients who died manifested pulmonary congestion, or wet lung, and respiratory difficulties during the terminal stage of the disease. In all patients before and during the terminal event, mild-to-moderate hematuria, and in two RBC in CSF, was observed. In one patient there was mild hemoperitoneum at the terminal event. The urine organic acids indicated increased excretion of ethylmalonic, methylsuccinic, glutaric, and adipic acids. The patients invariably showed lactic acidosis, but no ketosis, during and in between the acidotic attacks of the disease. The acylcarnitine profile in blood of two patients showed a pronounced increase in C4 and C5 carnitine esters. In three patients, biopsies from petechiae indicated absence of an immune event, showing only fresh hemorrhage. An immunologic study in one patient was normal for the suppressor:cytotoxic lymphocyte ratio and concentration of interleukin-2 receptor during and in between hemorrhagic attacks. The cytochrome c oxidase activity in fibroblasts was normal. The rate of oxidation of glucose, leucine, isoleucine, valine, propionate and butyrate by fibroblasts was normal. The disease is not responsive to treatment with riboflavin, ascorbic acid, vitamin E, glycine, or carnitine. One patient remained stable on prolonged large doses of methylprednisolone. The biochemical defect leading to ethylmalonic aciduria in this disease remains unknown.

Acidosis↗
PubMed1994

3-Methylglutaconic aciduria: ten new cases with a possible new phenotype.

3-Methylglutaconic aciduria is an organic aciduria with diverse phenotypic presentations. In more than half of the cases it is a 'neurologic or silent organic aciduria', and, except for one subtype, the biochemical defect is unknown. This report describes 10 new patients. Four of them presented with early global neurologic involvement and arrested development. They rapidly became demented, developed myoclonus or tonic-clonic seizures, spastic quadriplegia, deafness and blindness, and died. Three had acidosis and hypoglycemia neonatally; later, myoclonus and deafness, and eventually severe mental retardation and spastic quadriplegia developed. One patient died. In three children who presented with sudden onset of extrapyramidal tract symptoms, with or without optic atrophy, the clinical presentation was significantly different from that described either for 'unspecified' type or for Costeff syndrome. All three patients showed clinical improvement soon after treatment with coenzyme Q.

Acidosis↗
PubMed1994

A new patient with alpha-ketoglutaric aciduria and progressive extrapyramidal tract disease.

A 4.5-year-old boy with chronic progressive encephalopathy is described. The clinical presentation initially included seizures and hypotonia which later evolved into severe extrapyramidal disease and dementia. The gas chromatography/mass spectrometry (GC/MS) analysis of urine indicated that alpha-ketoglutarate was increased 210 times and aconitic acid 80 times. No disturbance of acid/base balance, lactic acid or ammonia metabolism accompanied this clinical picture. The fibroblasts contained 29% of normal alpha-ketoglutarate dehydrogenase activity, while the activity of another mitochondrial marker enzyme, glutamate dehydrogenase, was normal. The neuroimaging studies revealed bilateral striatal necrosis. The clinical and biochemical findings were almost identical to two previously reported patients. Experience with this patient emphasizes the need for detailed organic acid biochemical investigation in any progressive encephalopathy and that extrapyramidal tract signs should evoke the possibility of alpha-ketoglutaric aciduria, among other 'neurologic organic acidemias'.

Basal Ganglia Diseases↗
PubMed1994

3-Ketothiolase deficiency: a review and four new patients with neurologic symptoms.

3-Ketothiolase deficiency (3KTD) manifests with intermittent acidosis and is due to deficiency of mitochondrial 2-methylacetoacetate thiolase. Only 22 patients have been previously reported. Although its variable clinical presentation is recognized, the associated neurological findings have not been detailed. We report four new patients all with significant neurological symptoms. Three patients were examined with MRI of the brain which showed increased T2 intensity within the posterior lateral part of the putamen bilaterally. In two the MRI was otherwise normal; in one delayed myelination was also seen. These MRI putaminal findings may be typical enough to suggest the diagnosis of 3KTD. Two of the three had abnormal EEGs; one had an abnormal VEP. 3KTD can thus occur as an organic acidemia associated with encephalopathy.

Acetyl-CoA C-Acyltransferase↗
PubMed1994

Unusual presentations of propionic acidemia.

The files of 25 patients with propionic acidemia (PA), followed by the Inborn Errors of Metabolism Service (IEMS) at King Faisal Specialist Hospital and Research Centre (KFSH & RC) from 1990 to 1993, were studied retrospectively. In 14 patients PA presented acutely with acidosis, hyperammonemia and thrombocytopenia, while in 11 patients the presentation of the disease was unusual. In the latter group, two neonates with PA initially appeared as a primarily hyperammonemic metabolic disease. In two other neonates the vomiting was so severe that they were diagnosed as intestinal obstruction in referral hospitals. The presentation in three infants was primarily as an immune disorder. In four infants, PA appeared as an acute or chronic encephalopathy, i.e. as a silent organic acidemia, with few other findings of the disease. The clinical picture of PA includes facial and nipple dysmorphia, severe hypotonia and vomiting. Severe thrombocytopenia is the hallmark of the metabolic crisis. In one patient it was noticed late and caused intracranial hemorrhage, while in three others intracranial bleeding caused death. The prognosis in PA remained grave despite rigorous treatment. Only seven of the 25 PA patients remained to have a normal life-style, while eight patients expired. The diagnosis is readily achieved by urine gas chromatography/mass spectrometry (GC/MS), by tandem mass spectrometry (MS/MS), or by enzyme analysis of fibroblasts. While there may be both examiner- and patient-related reasons for the variations in the presentation of PA, one other reason may be the heterogeneity of the molecular defect in propionyl-CoA carboxylase.

Abnormalities, Multiple↗
PubMed1994

4-Hydroxybutyric aciduria.

The clinical findings in six patients from three families with 4-hydroxybutyric aciduria are described. The onset of disease was in early infancy in all cases. All infants presented with severe global delay and severe hypotonia, and all patients had seizure disorder. Eye findings included optic atrophy in two patients, and retinitis pigmentosa in one. Three patients had choreoathetosis, two had myoclonus and one had severe dystonia. The urine 4-hydroxybutyric acid was 300-1000 times that of normal, and other organic acids related to its further metabolism or to its inhibitory effect on beta-oxidation were also increased. The administration of vigabatrine rapidly reduced the excretion of 4-hydroxybutyric acid promptly, and in the long-term its excretion could be kept at 80-200 times that of normal. However, the clinical course of the disease improved in only two, remained the same in two, and worsened in the remaining two patients.

Adult↗
PubMed1994

The clinical spectrum of biotin-treatable encephalopathies in Saudi Arabia.

Ten patients with biotin-dependent, chronic progressive encephalopathies were studied retrospectively. In four patients, the underlying disease was either total or partial deficiency of biotinidase. In one patient, the disease was caused by a lack of holocarboxylase synthetase activity. Four patients presented with Leigh encephalopathy. However, a biochemical defect could not always be confirmed. All patients required the administration of large doses of biotin to maintain normal neurologic function.

Amidohydrolases↗
PubMed1994

Movement disorders in childhood organic acidurias. Clinical, neuroimaging, and biochemical correlations.

Over the last 5 years the Pediatric Neurology service at King Faisal Specialist Hospital and Research Centre (KFSH&RC) has seen 131 infants and children with movement disorders. Forty-nine (37%) had identifiable biochemical defects, 25 of which were organic acidemias. Nineteen of 29 patients with dystonia had organic acidemias, primarily glutaric aciduria type 1 (7 patients), bilateral striatal necrosis (4 patients), and 3-methyl glutaconic aciduria (3 patients). All patients with parkinsonian rigidity (n = 11) had organic acidemias; again, the greatest number accounted for by glutaric aciduria type 1 (7 patients), who had both parkinsonian rigidity combined with dystonia. Myoclonus occurred in only 1 of 25 and chorea in 7 of 25 patients with organic acidemias. At the least all patients had bilateral lesions of putamen and head of caudate, seen best in MRI brain scans as increased T2 signal intensities with normal volume, and later with volume loss.

Acidosis↗
PubMed1994

Neurophysiologic correlates of organic acidemias: a survey of 107 patients.

The files of 107 patients with 19 different types of organic acidemia were reviewed retrospectively. Approximately 50% of the patients had abnormal electroencephalogram (EEG) at the time of initial study. In patients who had serial studies, the EEG deteriorated in 38% and improved in 15%. The predominant EEG abnormality encountered was slowing of the background activity in various degrees. Focal or generalized paroxysmal activity occurring in conjunction with slow background activity indicated a poor prognosis. Brainstem auditory evoked potentials (BAEP), visual evoked potentials (VEP), and somatosensory evoked potentials (SEP) were analyzed. The VEP was abnormal in 44%, BAEP in 39%, and SEP in 29% of the patients. Given the magnitude and frequency by which neurophysiological abnormalities occur in organic acidemias, neurophysiology testing provides complementary functional information and has an important place in the clinical work-up of these diseases.

Acidosis↗
PubMed1994

Ataxia-ocular motor apraxia syndrome: an investigation of cellular radiosensitivity of patients and their families.

Although ataxia-ocular motor apraxia (AOA) has been described as a disease entity mimicking ataxia telangiectasia (AT), no radiobiological studies have been carried out on cells from patients with AOA to find their possible relationship to AT. In the present study, cultured fibroblasts from three patients with AOA and their asymptomatic relatives (parents and sibs) were, therefore, compared with those from a classical AT homozygote, an AT heterozygote, and four healthy subjects for cell survival after acute and chronic irradiation. While a moderately increased cellular sensitivity (compared to normal) was observed in two AOA patients and most of their relatives, the degree of their radiosensitivity was quite different from that of the AT homozygote after both acute and chronic irradiation. One AOA patient exhibited increased cellular sensitivity similar to that of a classical AT homozygote up to 4% survival level after chronic irradiation but not after acute irradiation. A comparison of peripheral blood lymphocytes from two AOA patients, an AT homozygote, and two normal controls for spontaneous and (acute) radiation induced chromosomal breaks also failed to show any similarity between AOA and AT. These data support the notion that AOA is different from classical AT, and may represent a distinct disease entity controlled by specific gene(s), or compound heterozygotes involving different AT genes promoting the manifestation of AOA characteristics.

Adolescent↗
PubMed1994

Sanfilippo type D presenting with acquired language disorder but without features of mucopolysaccharidosis.

A 7-year-old girl presented with a language disorder reminiscent of verbal auditory agnosia. Later, she proved to have defective N-acetylglucosamine-6-sulfate sulfatase, the enzyme deficient in Sanfilippo D syndrome. She did not show clinical features of mucopolysaccharidosis. The language disorder had a fluctuating course, which eventually evolved into a progressive dementing encephalopathy.

Agnosia↗
PubMed1993

A preliminary study of the relationship between central auditory processing disorder and attention deficit disorder.

Fifteen boys aged six to ten who met the criteria for attention deficit disorder (ADD) were compared with ten boys who did not have ADD in a double-blind, placebo-controlled, single-crossover study of methylphenidate. To assess the degree of overlap between ADD and central auditory processing disorder (CAPD), all subjects were assessed on parent and teacher behavior rating scales, as well as a battery of CAPD tests at baseline and after three and six weeks of treatment. Twelve of the 15 subjects with ADD and none of the subjects without ADD met the criteria for CAPD. The subjects with ADD also responded to stimulant treatment on the measures of both ADD and CAPD. The overlap in the symptomatology of these disorders, the finding that the criteria for both disorders were met in 12 of 15 cases and the sensitivity of both ADD and CAPD measures to treatment with methylphenidate suggest that ADD and CAPD are closely related disorders. The implications of these results are three-fold. First, sustained attention is a critical feature of performance on CAPD tests and the current diagnostic criteria for CAPD make a clinical separation of the two disorders problematic. Second, stimulants appear to be a useful treatment for the symptoms of both ADD and CAPD. Third, CAPD tests may be a useful measure of ADD symptomatology and response to stimulants.

Analysis of Variance↗
PubMed1992

Neurometabolic diseases at a national referral center: five years experience at the King Faisal Specialist Hospital and Research Centre.

Of 910 children under the age of 12 years referred to the national center, we were able to assign an etiology to 473 (52%). This group consisted of lysosomal storage diseases (32%), amino acid disorders (14%), organic acid disorders (16%), various chromosome abnormalities and syndromes with dysmorphia or brain dysgenesis (26%), and various other metabolic diseases (12%). While such amino acidemias as branched-chain amino acidemia (MSUD) in classic and intermediate forms (44%) and hyperphenylalaninemia (PKU) due to 6-pyruvoyltetrahydropterin synthase deficiency (6PTSD) (19%) were common, classic PKU was rare (16%). Methylmalonic acidemia (31%), 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (16%), and propionic acidemia (12%) were encountered more frequently than other types of organic acidemias. When compared to the number of referred Down's syndrome patients, the results suggested the birth of at least one infant with neurometabolic disease per 50 births. Five tribes of Saudi Arabia constituted 26% of the diagnosable neurometabolic diseases. Diseases such as MSUD, 6 PTSD, Sanfilippo syndrome type B, methylmalonic acidemia, homocystinuria, GM2 gangliosidosis Sandhoff variant, infantile central nervous system spongy degeneration (Canavan disease), and neuraminidase deficiency showed definite tribal occurrence. In addition, 32% to 42% of the definitely diagnosed, and 25% to 87% of patients with probable neurometabolic disease but without a definable etiology, had more than one sibling affected. It is concluded that the many rare autosomal diseases of Saudi Arabia are due to "founder effect" created by marriages occurring within tribal and extended family boundaries.

Brain Diseases, Metabolic↗