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J J McGill

Publications and source records attributed to J J McGill.

At least 19 recordsLinked to original sources
PubMed2006

Seizures, ataxia, developmental delay and the general paediatrician: glucose transporter 1 deficiency syndrome.

AIM: Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an important condition for the general paediatrician's differential armamentarium. We describe a case series of eight patients in order to raise awareness of this treatable neurometabolic condition. The diagnosis of GLUT1-DS is suggested by a decreased absolute cerebrospinal fluid (CSF) glucose value (<2.2 mmol/L) or lowered CSF: plasma glucose ratio (<0.4). METHODS: This is a review of eight Queensland patients with GLUT1-DS. The clinical presentation, clinical course, laboratory investigations and treatment outcomes are discussed. RESULTS: The clinical features noted in our patient cohort include combinations of ataxia, developmental delay and a severe seizure disorder that is refractory to anticonvulsant medications. Seizures are the most common clinical manifestation and may be exacerbated by phenobarbitone. The paired CSF: plasma glucose results ranged from 0.2 to 0.39 (normal <0.6) with an average of 0.33. 3-O-Methyl-D-Glucose uptake and GLUT1 Genotyping analysis have been performed on five patients thus far. Rapid and impressive seizure control was observed in 100% of our patients once the ketogenic diet was instituted, with half of the cohort being able to wean completely from anticonvulsants. CONCLUSION: Children presenting with a clinical phenotype consisting of a refractory seizure disorder, ataxia and developmental delay should prompt the consideration of Glucose transporter 1 deficiency syndrome. While the diagnostic test of lumbar puncture is an invasive manoeuvre, the diagnosis provides a viable treatment option, the ketogenic diet. GLUT1-DS displays clinical heterogeneity, but the value of early diagnosis and treatment is demonstrated by our patient cohort.

3-O-Methylglucose↗
PubMed2005

Histopathology and fibrillin-1 distribution in severe early onset Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant condition which may involve the cardiovascular, ocular, skeletal, and other systems. Mutations causing MFS are found in the FBN1 gene, encoding fibrillin-1, an extracellular matrix protein involved in microfibril formation. In the most severe cases, mutations are generally found in exons 24-32, and children with these mutations usually die in the first years of life, of cardiopulmonary failure. We present clinical, molecular and histopathological studies on a patient with severe early onset MFS. He has a mutation in exon 25 of FBN1, a G>A transition at nucleotide position 3131 that converts the codon TGC, coding for cysteine at position 1044, to TAC, coding for tyrosine (C1044Y). This has resulted in abnormalities of the extracellular matrix and a severe clinical phenotype, although he has survived to the age of 14 years.

Adolescent↗
PubMed1999

Carbohydrate-deficient glycoprotein syndrome in a newborn with an unbalanced chromosomal translocation.

UNLABELLED: Carbohydrate-deficient glycoprotein syndromes may occur as a primary result of distinct genetic disruption of the enzymes involved in processing the carbohydrate moeities of glycoproteins. They may also occur due to a number of secondary defects in glycosylation. CONCLUSION: A female infant with an unbalanced chromosomal translocation [46,XX,der(21)t(17;21) (p13.1;q22.11)mat.ish der(21)t(17;21) (D17S375 x 3, D21S65-)] and with biochemical and clinical features of a carbohydrate deficient glycoprotein syndrome is reported. This chromosomal disruption is another secondary cause of the disorder.

Congenital Disorders of Glycosylation↗
PubMed1999

Mitochondrial DNA mutations at nucleotide 8993 show a lack of tissue- or age-related variation.

Two pathogenic mitochondrial DNA mutations, a T-to-G substitution (8993T > G) and a T-to-C substitution (8993T > C), at nucleotide 8993 have been reported. We describe 13 pedigrees with mitochondrial DNA mutations at nucleotide 8993; 10 pedigrees with the 8993T > G mutation and three with the 8993T > C mutation. Prenatal diagnosis of the nucleotide 8993 mutations is technically possible. However, there are three major concerns: (i) that there is variation in mutant loads among tissues; (ii) that the mutant load in a tissue may change over time; and (iii) that the genotype-phenotype correlation is not clearly understood. We have used the 13 pedigrees to determine specifically the extent of tissue- and age-related variation of the two mutations at nucleotide 8993 in the mitochondrial DNA. The tissue variation was investigated by analysing two or more different tissues from a total of 18 individuals. The age-related variation of the mutation was investigated by comparing the amount of both mutations in blood taken at birth and at a later age. No substantial tissue variation was found, nor was there any substantial change in the proportion of either mutation over periods of 8-23 years in the four individuals studied. In addition, we noted that two features were remarkably common in families with nucleotide 8993 mutations, namely (i) unexplained infant death (8 cases in 13 pedigrees); and (ii) de novo mutations (5 of the 10 8993T > G pedigrees).

Aging↗
PubMed1999

Mammographic determination of breast volume: comparing different methods.

OBJECTIVE: The purpose of this study was to compare the accuracy and reproducibility of different methods for calculating breast volume when using measurements made on mammograms. MATERIALS AND METHODS: The volumes of 32 breasts were determined by pathologic evaluation of mastectomy specimens. Two radiologists independently measured breast height and width on the preoperative craniocaudal mammograms and measured height, width, and width at half-height on mediolateral oblique mammograms. Compression thicknesses used on the craniocaudal and mediolateral oblique projections were recorded. Volume was then calculated using six different formulas. The accuracy of each method was determined and compared using bivariate and univariate linear regression analyses. Interobserver variability in measurement was also assessed. RESULTS: The most accurate method for calculating breast volume was the one that assumed a half-elliptic cylinder shape for the compressed breast in the craniocaudal projection. Measurements made on the craniocaudal view were more reproducible than those made on the mediolateral oblique view. CONCLUSION: Breast volume can be accurately and reproducibly determined on mammograms by making two measurements on the craniocaudal view and knowing the compression thickness. This information may be useful to plastic surgeons, investigators who study parenchymal patterns, and physicians who examine cancer patients being considered for breast conservation surgery.

Adult↗
PubMed1995

Molecular cytogenetic characterisation of a small ring X chromosome in a Turner patient and in a male patient with congenital abnormalities: role of X inactivation.

The association of small accessory marker chromosomes in man with specific abnormalities has been difficult to define owing to variations in the chromosome origin and the size of the markers. In a patient with typical Turner phenotype and a 45,X/46,X, + mar karyotype the marker was shown to be a small portion of the long arm of the X chromosome which included the centromere and XIST, a candidate gene for the X inactivation centre. Therefore the lack of any additional abnormalities was attributed to inactivation of the portion of the X chromosome in the marker. In a patient with a 47,XY, + mar karyotype the mar was a small ring X chromosome which did not contain the XIST gene. For both markers the short arm breakpoints were localised between UBE1 and DXS423E. The congenital abnormalities of the male patient were attributed to the lack of X inactivation of the small ring and therefore disomic expression of normal genes possessed by the marker.

Base Sequence↗
PubMed1993

Pneumocystis carinii thyroiditis. Report of three cases and review of the literature.

Pneumocystis carinii infection of the thyroid gland has previously been described in only four living patients with acquired immunodeficiency syndrome, three of whom had been receiving inhaled pentamidine prophylaxis against P carinii pneumonia. We treated three additional patients with P carinii thyroid involvement, all of whom were receiving aerosolized pentamidine. Two of our patients presented with clinical features suggestive of subacute granulomatous thyroiditis. The diagnosis of P carinii in our patients, as well as in the previously described patients, was established by thyroid fine-needle aspiration and Gomori's silver methenamine stains. The recent emergence of P carinii infection of the thyroid gland is likely related to the use of inhaled pentamidine prophylaxis, which appears to predispose to the development of extrapulmonary pneumocystosis. Clinicians need to be aware of the possibility of P carinii thyroiditis and should use aspiration and Gomori's methenamine silver staining in studying patients with the acquired immunodeficiency syndrome who have a painful (or other unexplained) thyroid mass so as to be able to initiate prompt and appropriate therapy.

AIDS-Related Opportunistic Infections↗
PubMed1992

3-Methylglutaconic aciduria: a marker for as yet unspecified disorders and the relevance of prenatal diagnosis in a 'new' type ('type 4').

The Mendelian disorder known as 3-methylgutaconic aciduria (McKusick 250950) gives evidence of allelic and locus heterogeneity. Type 1 has a mild clinical phenotype and confirmed 3-methylgutaconyl-CoA hydratase deficiency; inheritance is autosomal recessive. Other forms have major clinical manifestations and subdivide into X-linked (type 2), a form in Iraqi Jews with optic atrophy (so-called type 3); and untyped (putative autosomal recessive) forms without identified enzyme defects. In the latter, 3-methylglutaconic aciduria may simply be a marker for another metabolic disorder. We describe a male proband with 3-methylglutaconic aciduria designated here as 'type 4' (autosomal recessive, with severe psychomotor phenotype and cerebellar dysgenesis). He is the offspring of Italian consanguineous parents. Born with congenital malformations, he has been followed for 18 years, showing profound developmental delay and cerebellar dysgenesis. Measures of hydratase activity in cultured fibroblasts from the proband and 11 additional patients (two with type 1 disease, 9 with either type 2 or an unspecified form) revealed deficient enzyme activity in type 1 cases and normal activity in the proband and the other 11 cases. Two of the untyped cases probably have 3-methylglutaconic aciduria of the type described here. Prenatal diagnosis in the form described here may be feasible by analysis of amniotic fluid metabolites in pregnancies at risk if the mother does not entirely remove elevated concentrations. A female sibling of the proband had normal metabolite values in amniotic fluid. Postnatal follow-up confirmed absence of the disease. We give the normal values for amniotic fluid and results on these additional fetuses at risk (none affected).

Amniotic Fluid↗
PubMed1992

Spasticity and white matter abnormalities in adult phenylketonuria.

A 19 year old male with phenylketonuria (PKU) developed a spastic paparesis 8 months after stopping his restricted phenylalanine diet. CT and MRI showed abnormalities of the deep cerebral white matter, and visual evoked response latencies were prolonged. The spasticity gradually improved over several months after resuming the PKU diet. A repeat MRI scan was unchanged. His brother also had PKU and ceased dietary restrictions, but his only neurological abnormality was a slight increase in the deep tendon reflexes of the lower limbs. CT and MRI of his brain was normal. DNA analysis showed that both brothers were homozygous for the same PKU mutation. These patients demonstrate that reversible neurological signs may develop in patients with classic PKU after ceasing dietary restrictions and that these may be associated with abnormalities seen on neuro-imaging.

Adult↗
PubMed1991

DNA fingerprinting: the utilization of minisatellite probes to detect a somatic mutation in the proteus syndrome.

Syndromes with localized or segmental abnormalities have been proposed to be the result of a somatic mutation leading to the presence of somatic mosaicism in the tissue. The Proteus syndrome, with its hemihypertrophy, macrodactyly and exostoses, has features which would indicate that the phenotype results from such events. The success of utilizing DNA fingerprint probes to detect somatic mutations in cancer raised the possibility that a similar approach might be successful in an investigation of two patients with the Proteus syndrome. Single band differences were detected with the probe 33.6 in a pair of monozygotic twins discordant for Proteus and in a comparison of tissue from normal and affected areas in another patient. These findings would appear to confirm the hypothesis that the Proteus syndrome results from a somatic mutation. Furthermore, the results indicate that DNA fingerprinting may offer a valuable technique for identifying probes for investigations of similar syndromes.

Abnormalities, Multiple↗
PubMed1990

Detection of heterozygotes for recessive alleles. Homocyst(e)inemia: paradigm of pitfalls in phenotypes.

Excess homocysteine in body fluids has been implicated as a factor in the pathogenesis of occlusive vascular disease (peripheral and cerebrovascular arterial disease, and perhaps coronary artery disease). Heterozygotes for inborn errors of homocysteine metabolism (transsulfuration or remethylation pathways) are much more frequent than are homozygotes/compounds. If heterozygotes are at increased risk (a question not addressed here), it is of interest to know whether they can be identified consistently by a "screening" measurement of blood homocyst(e)ine. We used hyperhomocyst(e)inemia (cystathioninemia beta-synthase deficiency) as a test case. From reviews of metabolite values in blood samples either fasting (11 articles) or after a methionine load (8 articles), and of measures of enzyme activity (12 articles), it is apparent that (1) The heterozygous phenotype cannot be identified consistently by any single measure (there is overlap with normal values); and (2) the exaggerated gene dosage effect (negative allelic complementation) present in most heterozygotes does not assist their classification. The failure of enzyme assay to distinguish heterozygotes consistently (relative to normal values) may reflect allelic heterogeneity. The failure of metabolic values to identify heterozygotes consistently reflects the local and global properties of the homeostatic system controlling the homocysteine pool size. The problem described here is a particular example of a general one in physiological and medical genetics, namely detection of heterozygotes for recessive alleles, affecting metabolic homeostasis, for purposes of medical intervention and for genetic counselling.

Alleles↗