ALG9-CDG: New clinical case and review of the literature.

Congenital disorders of glycosylation (CDG) are a group of metabolic diseases resulting from defects in glycan synthesis or processing. The number of subgroups and their phenotypic spectrums continue to expand with most related to deficiencies of N-glycosylation. ALG9-CDG (previously CDG-IL) is the result of a mutation in .

A rare case of Niemann-Pick disease type C without neurological involvement in a 66-year-old patient.

Unlabelled: The case of a 66 year-old female - the oldest known living patient with Niemann-Pick disease type C (NP-C) who remains free of any neurological or psychiatric manifestations 18 years after presentation - is presented. An incidental finding of massive splenomegaly was detected during a routine pelvic ultrasound. The pathology report after splenectomy showed the presence of lipid-laden macrophages.

The paradox of the carnitine palmitoyltransferase type Ia P479L variant in Canadian Aboriginal populations.

Investigation of seven patients from three families suspected of a fatty acid oxidation defect showed mean CPT-I enzyme activity of 5.9+/-4.9 percent of normal controls.

CDG-IL: an infant with a novel mutation in the ALG9 gene and additional phenotypic features.

We describe the second case of congenital disorder of glycosylation type IL (CDG-IL) caused by deficiency of the ALG9 a1,2 mannosyltransferase enzyme. The female infant's features included psychomotor retardation, seizures, hypotonia, diffuse brain atrophy with delayed myelination, failure to thrive, pericardial effusion, cystic renal disease, hepatosplenomegaly, esotropia, and inverted nipples. Lipodystrophy and dysmorphic facial features were absent.

The C677T methylenetetrahydrofolate reductase variant and third trimester obstetrical complications in women with unexplained elevations of maternal serum alpha-fetoprotein.

Introduction: The C677T MTHFR variant has been associated with the same third trimester pregnancy complications as seen in women who have elevations of maternal serum alpha-fetoprotein (MSAFP). We hypothesized that these women with third trimester pregnancy complications and MSAFP elevations would have an increased frequency of the variant compared to an abnormal study control group (women with MSAFP elevations without pregnancy complications) as well as to normal population controls.

Methods: Women who had unexplained elevations of MSAFP in pregnancy were ascertained retrospectively.

Outcome of the first 3-years of a DNA-based neonatal screening program for glutaric acidemia type 1 in Manitoba and northwestern Ontario, Canada.

Glutaric acidemia type 1 (GA1) is overrepresented in the aboriginal population of Island Lake, Manitoba, and northwestern Ontario who speak the Ojibway-Cree (Oji-Cree) dialect. The carrier frequency in these communities has been predicted to be as high as 1 in 10 individuals. Prior to beginning newborn screening for GA1 in May 1998, 18 of 20 affected patients diagnosed at this center have been from these high-risk communities.

Hepatic carnitine palmitoyltransferase I deficiency presenting as maternal illness in pregnancy.

The spectrum of clinical presentation of fatty acid oxidation defects (FAOD) continues to expand. One FAOD, L-3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been associated with liver disease in pregnancies involving a heterozygous mother carrying an affected fetus. Hepatic carnitine palmitoyltransferase (CPT I) deficiency typically presents as a Reyelike syndrome in children between 8 and 18 mo.

A simple screening test for fatty acid oxidation defects using whole-blood palmitate oxidation.

We report that measurement of whole-blood palmitate oxidation is a rapid and inexpensive screening test for fatty acid oxidation defects. The assay has been adapted from published assays using cultured fibroblasts or isolated white blood cells. Micro whole-blood samples are incubated with tritiated palmitic acid as substrate.

Familial neuroblastoma: report of a kindred with later age at diagnosis.

Purpose: To describe the clinical and biologic features of neuroblastoma (NB) in two siblings and their maternal second cousin.

Patients And Methods: NB was diagnosed in the siblings at 2 1/2 (patient 2) and 5 (patient 3) years of age. NB was diagnosed in their maternal second cousin (patient 1) when she was 7 years old.

Amerindian pyruvate carboxylase deficiency is associated with two distinct missense mutations.

We characterized the pyruvate carboxylase (PC) gene by PCR amplification, subcloning, and sequencing. The coding region has 19 exons and 18 introns spanning approximately 16 kb of genomic DNA. Screening both the cDNA and the gene of individuals with the simple A form of PC deficiency revealed an 1828G-->A missense mutation in 11 Ojibwa and 2 Cree patients and a 2229G-->T transversion mutation in 2 brothers of Micmac origin.

Two novel mutations in a Canadian family with aspartylglucosaminuria and early outcome post bone marrow transplantation.

Aspartylglucosaminuria (AGU) is a lysosomal storage disease caused by deficiency of aspartylglucosaminidase. The disease is overrepresented in the Finnish population, in which one missense mutation (Cys163Ser) is responsible for 98% of the disease alleles. The few non-Finnish cases of AGU which have been analyzed at molecular level have revealed a spectrum of different mutations.

Blood lactate and pyruvate concentrations, and their ratio during exercise in healthy children: developmental perspective.

Blood concentrations of lactate normally increase during and after intense exercise as does the ratio of concentrations of lactate to pyruvate (L:P). Since there appear to be differences in blood lactate concentrations on exercise, in muscle metabolic enzyme activities, and in anaerobic capacity between children and adults, we speculated that there would be age related differences in lactate and pyruvate concentrations, and their ratio among children. Whole blood concentrations of lactate and pyruvate were measured in 28 healthy children aged 7-17 years, split into three age groups: less than 11, 11-14, and 15-17 years.

A homoallelic Gly317-->Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites.

We have discovered a single homoallelic nucleotide substitution as the putative cause of the perinatal (lethal) form of hypophosphatasia in Canadian Mennonites. Previous linkage and haplotype analysis in this population suggested that a single mutational event was responsible for this autosomal recessive form of hypophosphatasia. The mutation is a guanosine-to-adenosine substitution at nucleotide position 1177 in exon 10 of the tissue nonspecific (liver/bone/kidney) alkaline phosphatase gene.

Symptomatic and asymptomatic methylenetetrahydrofolate reductase deficiency in two adult brothers.

We describe two brothers with 5,10-methylene tetrahydrofolate reductase (MTHFR) deficiency. The younger patient first developed limb weakness, incoordination, paresthesiae, and memory lapses at age 15 years, and by his early twenties he was wheelchair bound. His older brother remains asymptomatic at age 37 years.

Atypical features of the hepatic form of carnitine palmitoyltransferase deficiency in a Hutterite family.

We describe hepatic carnitine palmitoyltransferase (CPT I) deficiency in three children (a brother and sister and their second cousin) from an extended inbred Hutterite kindred. The patients were first seen between 8 and 18 months of age with recurrent episodes of hypoketotic hypoglycemia accompanied by a decreased level of consciousness and hepatomegaly. One patient had two Reye syndrome-like episodes.

Carrier detection in glutaric aciduria type I using interleukin-2-dependent cultured lymphocytes.

Cultured interleukin 2 (IL-2)-dependent leukocytes from 13 patients with glutaric aciduria type I, 12 obligate carriers, 105 family members and 31 normal controls were assayed for glutaryl-CoA dehydrogenase activity. Of the 13 affected patients, 10 (all Ojibway Indian) had residual enzyme activity (2-13% of control) and 3 patients (all non-Indian) had undetectable enzyme activity. There was partial overlap between the distribution of enzyme activity in obligate heterozygotes and in normal controls (mean values +/- SD: 6.

Glutaric aciduria type I: a common cause of episodic encephalopathy and spastic paralysis in the Amish of Lancaster County, Pennsylvania.

We have diagnosed type I glutaric aciduria (GA-I) in 14 children from 7 Old Order Amish families in Lancaster County, Pennsylvania. An otherwise rare disorder, GA-I appears to be a common cause of acute encephalopathy and cerebral palsy among the Amish. The natural history of the disease, which was previously unrecognized in this population, is remarkably variable and ranges from acute infantile encephalopathy and sudden death to static extrapyramidal cerebral palsy to normal adult.

Increased prevalence of hereditary metabolic diseases among native Indians in Manitoba and northwestern Ontario.

Objective: To compare the prevalence of hereditary metabolic diseases in the native and non-native populations of Manitoba and northwestern Ontario.

Design: Retrospective analysis.

Setting: Children's Hospital, Winnipeg.

Hyperphosphatemia in infantile hypophosphatasia: implications for carrier diagnosis and screening.

Twenty obligate carriers of infantile hypophosphatasia (HOPS), a severe autosomal recessive metabolic bone disorder, were studied and compared with 36 controls. Decreased serum alkaline phosphatase activity and increased urinary phosphoethanolamine excretion were confirmed in the HOPS carriers. Relative hyperphosphatemia was documented for the first time in the carriers.

Increased plasma pyridoxal-5'-phosphate levels before and after pyridoxine loading in carriers of perinatal/infantile hypophosphatasia.

We measured plasma levels of pyridoxal-5'-phosphate (PLP), a cofactor form of vitamin B6 and apparent natural substrate for alkaline phosphatase (ALP), in carriers and in non-carriers of the severe perinatal and infantile forms of hypophosphatasia, both before and after an oral load of pyridoxine (i.e. 1/3 mg/kg body weight).

Newborn screening for galactosemia: a new method used in Manitoba.

In July 1983, the Manitoba Perinatal Screening Programme modified its existing procedure for neonatal screening for galactosemia by introducing quantitation of total galactose plus galactose-1-phosphate from dried blood spots using the Multistat centrifugal analyzer. The first 4 years of experience with this method in combination with the Beutler spot test for galactose-1-phosphate uridyl transferase activity is the subject of this report. Of 70,336 newborns screened, 142 (0.