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Biomedical subjects

A A Morris

Publications and source records attributed to A A Morris.

At least 19 recordsLinked to original sources
PubMed2006

Glucose and leucine kinetics in idiopathic ketotic hypoglycaemia.

AIMS: To investigate glucose and leucine kinetics in association with metabolic and endocrine investigations in children with ketotic hypoglycaemia (KH) in order to elucidate the underlying pathophysiology. METHODS: Prospective interventional study using stable isotope tracer in nine children (mean age 4.23 years, range 0.9-9.8 years; seven males) with KH and 11 controls (mean age 4.57 years, range 0.16-12.3 years; four males). RESULTS: Plasma insulin levels were significantly lower in KH compared to subjects in the non-KH group. Plasma ketone body levels were significantly higher in KH than in non-KH. Basal metabolic rate was significantly higher in subjects with KH (45.48+/-7.41 v 31.81+/-6.72 kcal/kg/day) but the respiratory quotients were similar in both groups (KH v non-KH, 0.84+/-0.05 v 0.8+/-0.04. Leucine oxidation rates were significantly lower in children with KH (12.25+/-6.25 v 31.96+/-8.59 micromol/kg/h). Hepatic glucose production rates were also significantly lower in KH (3.84+/-0.46 v 6.6+/-0.59 mg/kg/min). CONCLUSIONS: KH is caused by a failure to sustain hepatic glucose production rather than by increased glucose oxidation rates. Energy demand is significantly increased, whereas leucine oxidation is reduced.

Alanine↗
PubMed2003

Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPT II) deficiency.

Carnitine palmitoyltransferase type II (CPT II) deficiency has three basic phenotypes, late-onset muscular (mild), infantile/juvenile hepatic (intermediate) and severe neonatal. We have measured fatty acid oxidation and CPT II activity and performed mutation studies in 24 symptomatic patients representing the full clinical spectrum of disease. Severe and intermediate phenotypes show a clear correlation with biochemical indices and genetic analysis revealed causative mutations in most patients. Studies of mild phenotypes suggest a more complex interaction, with higher residual fatty acid oxidation, a wider range of CPT II activity (10-60%) but little evidence of genotype-phenotype correlation. Residual CPT II mutant protein from myopathic patients shows thermal instability at 41 degrees C. The common 'polymorphisms' V3681 and M647V are strikingly overrepresented in the myopathic patients, the implication being that they may significantly influence the manifestation of clinical disease and could therefore potentially be considered as a susceptibility variants. Among myopathic individuals, males comprised 88% of patients, suggesting increased susceptibility to clinical disease. A small number of symptomatic patients appear to have significant residual CPT II activity (42-60%) The synergistic interaction of partial deficiencies of CPT II, muscle adenosine monophosphate deaminase and possibly other enzymes of muscle energy metabolism in the aetiology of episodic myopathy deserves wider consideration.

AMP Deaminase↗
PubMed2001

ARC syndrome: an expanding range of phenotypes.

AIM: To describe the clinical phenotype in infants with ARC syndrome, the association of arthrogryposis, renal tubular acidosis, and cholestasis. METHODS: The medical records for six patients with ARC syndrome were reviewed, presenting over 10 years to three paediatric referral centres. RESULTS: All patients had the typical pattern of arthrogryposis. Renal Fanconi syndrome was present in all but one patient, who presented with nephrogenic diabetes insipidus. Although all patients had severe cholestasis, serum gamma glutamyltransferase values were normal. Many of our patients showed dysmorphic features or ichthyosis. All had recurrent febrile illnesses, diarrhoea, and failed to thrive. Blood films revealed abnormally large platelets. CONCLUSIONS: ARC syndrome exhibits notable clinical variability and may not be as rare as previously thought. The association of Fanconi syndrome, ichthyosis, dysmorphism, jaundice, and diarrhoea has previously been reported as a separate syndrome: our observations indicate that it is part of the ARC spectrum.

Acidosis, Renal Tubular↗
PubMed2000

Inborn errors of metabolism around time of birth.

Inborn errors of metabolism commonly present around the time of birth. Although most affected babies are born healthy and subsequently deteriorate, some disorders may present at (or shortly after) birth and a few may be detected by antenatal ultrosonography. In many cases, it is important that the diagnosis is made quickly and a strategy to identify those at high risk is proposed. Treatment should not be delayed for a definitive diagnosis.

Humans↗
PubMed1999

Expanding the forensic German mitochondrial DNA control region database: genetic diversity as a function of sample size and microgeography.

Mitochondrial DNA control region sequences were determined in 109 unrelated German Caucasoid individuals from north west Germany for both hypervariable regions 1 (HV1) and 2 (HV2) and 100 polymorphic nucleotide positions (nps) were found, 63 in HV1 and 37 in HV2. A total of 100 different mtDNA lineages was revealed, of which 7 were shared by 2 individuals and 1 by 3 individuals. The probability of drawing a HV1 sequence match within the north west Germans or within published sets of south Germans and west Austrians is similar (within a factor of 2) to drawing a sequence match between any two of these three population samples. Furthermore, HV1 sequences of 700 male inhabitants of one village in Lower Saxony were generated and these showed a nearly linear increase of the number of different haplotypes with increasing number of individuals, demonstrating that the commonly used haplotype diversity measure (Nei 1987) for population samples tends to underestimate mtDNA diversity in the actual population.

Austria↗
PubMed1999

Novel mutations in patients with fructose-1,6-bisphosphatase deficiency.

Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive disorder of gluconeogenesis. Mutations have recently been identified in Japanese patients but none has been reported in patients of other ethnic backgrounds. We have undertaken sequence analysis on genomic DNA isolated from leukocytes of four patients with FBPase deficiency. Homozygous mutations were found in all four cases. One patient was homozygous for the common mutation identified in Japanese patients (960-961insG in exon 7). The other three patients were all homozygous for novel mutations (35delA in exon 1,778G-->A in exon and 966delC in exon 7). Normal and mutant FBPases were expressed in prokaryotic (E. coli TG2) and eukaryotic (COS1) cells. In cell-free extracts the mutant proteins were enzymatically inactive, indicating that the mutations are responsible for the disease. In one affected family, molecular genetic analysis allowed the diagnosis to be excluded promptly in a newborn child 3 days after birth.

Animals↗
PubMed1999

Mitochondrial respiratory chain disorders and the liver.

Mitochondrial respiratory chain disorders are an established cause of liver failure in early childhood but they are probably under-diagnosed, partly due to under-recognition and partly due to the difficulty of investigation. It is particularly important to look for mitochondrial disorders if the liver disease presents with hypoglycaemia and lactic acidaemia or if it is accompanied by neurological, muscle or renal tubular abnormalities. Respiratory chain defects have been demonstrated in a number of patients who die of liver failure following severe epilepsy; this includes at least some cases of Alpers syndrome or 'progressive neuronal degeneration of childhood'. In mitochondrial liver disease, histology usually shows steatosis, often accompanied by fibrosis, cholestasis and loss of hepatocytes. Unless the clinical picture suggests a particular syndrome, such as Pearson syndrome, biochemical assays and histochemistry should be the initial investigations. Ideally, investigations should be carried out on liver as well as more standard tissues, such as muscle, since defects can be tissue-specific. Nuclear defects and mtDNA point mutations are probably responsible for many cases of mitochondrial liver disease but, as yet, the only identified molecular abnormalities are mtDNA rearrangements and mtDNA depletion. Treatment of mitochondrial liver disease is unsatisfactory. If the disease is confined to the liver, transplantation may be appropriate but in several patients transplantation has been followed by the appearance of disease in other organs, particularly the brain.

DNA, Mitochondrial↗
PubMed1998

Hyperammonaemia due to Klebsiella infection in a neuropathic bladder.

A boy with a neuropathic bladder and a single hydronephrotic kidney developed hyperammonaemic encephalopathy during a urinary tract infection with Klebsiella oxytoca. Although particularly associated with Proteus infections and prune belly syndrome, hyperammonaemia can complicate infection with any urease-producing bacteria if there is urinary stasis.

Ammonia↗