PubMed Health⌕ Search

Biomedical subjects

P M Fernhoff

Publications and source records attributed to P M Fernhoff.

45 records · Page 3Linked to original sources
PubMed1976

Association of D/D translocations with fetal wastage and aneuploidy. A report of four families.

Four families are described with a t(13q14q) segregating. Two of them were identified through index cases with Down's syndrome; their karotypes revealed the unusual 46,XY, -13, -14, +t(13q14q), +21. The other two families were identified through a chromosomal study of parents with repeated spontaneous abortions. Analysis of data on 3 of these 4 families and on 7 other from the published reports showed no evidence of increased fetal wastage among 13/14 carriers. However, the risk of producing offspring with various types of aneuploidy may be greater among carriers than among persons with a normal chromosome pattern. Qualitative and quantitative differences in D/D translocations may account for the observed variation in clinical findings. These differences add to the problem of determining genetic risks from an analysis of grouped data.

Adult↗
PubMedDate not supplied

Lymphedema as a postulated cause of cutis verticis gyrata in Turner syndrome.

Unusual skin lesions were present at birth in four infants with Turner syndrome. The skin changes in these patients appear to have resulted either from in utero entrapment or pinching of edematous skin or from redundant skin remaining after in utero resolution of lymphedema. Distention by lymphedema is thought to cause several of the phenotypic characteristics seen in patients with Turner syndrome, including nuchal webbing and nail changes. In three of these patients the clinical appearance of the skin changes was similar to cutis verticis gyrata, marked by fixed thickened plaques in folds.

Female↗
PubMedDate not supplied

Defective urinary carnitine transport in heterozygotes for primary carnitine deficiency.

PURPOSE: Primary carnitine deficiency is an autosomal recessive disorder caused by defective carnitine transport and manifests as nonketotic hypoglycemia or skeletal or heart myopathy. METHODS: To define the mechanisms producing partially reduced plasma carnitine levels in the parents of affected patients, we examined carnitine transport in vivo and in the fibroblasts of a new patient and his heterozygous parents. RESULTS: Kinetic analysis of carnitine transport in fibroblasts revealed an absence of saturable carnitine transport in the proband's cells and a partially impaired carnitine transport in fibroblasts from both parents, whose cells retained normal Km values toward carnitine (6-9 microM) but reduced Vmax. At steady state, normal fibroblasts accumulated carnitine to a concentration that was up to 80 times the extracellular value (0.5 microM). By contrast, cells from the proband had minimal carnitine accumulation, and cells from both parents had intermediate values of carnitine accumulation. Plasma carnitine levels were slightly below normal in both heterozygous, yet clinically normal, parents and in the paternal grandfather and the maternal grandmother. To define the mechanism producing partially decreased carnitine levels, we studied urinary carnitine losses in heterozygous parents compared with controls. Urinary losses increased linearly (P < 0.05) with plasma carnitine levels in normal controls. When urinary carnitine losses were normalized to plasma carnitine levels, a significant difference was observed between controls and heterozygous individuals (P < 0.01). CONCLUSIONS: These results indicate that fibroblasts from heterozygotes for primary carnitine deficiency have a decreased capacity to accumulate carnitine and that heterozygotes have increased urinary losses, which may contribute to their reduced plasma carnitine levels.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review.

Medium chain acyl-CoA dehydrogenase (MCAD) is a tetrameric flavoprotein essential for the beta-oxidation of medium chain fatty acids. MCAD deficiency (MCADD) is an inherited error of fatty acid metabolism. The gene for MCAD is located on chromosome one (1p31). One variant of the MCAD gene, G985A, a point mutation causing a change from lysine to glutamate at position 304 (K304E) in the mature MCAD protein, has been found in 90% of the alleles in MCADD patients identified retrospectively. There is a high frequency of MCADD among people of Northern European descent, which is believed to be due to a founder effect. MCADD is inherited in an autosomal recessive manner. Of patients clinically diagnosed with MCADD, 81% who have been identified retrospectively are homozygous for K304E, and 18% are compound heterozygotes for K304E. Clinical data on the probability of clinical disease indicates that MCADD patients are at risk for the following outcomes: hypoglycemia, vomiting, lethargy, encephalopathy, respiratory arrest, hepatomegaly, seizures, apnea, cardiac arrest, coma, and sudden and unexpected death. Long-term outcomes include developmental and behavioral disability, chronic muscle weakness, failure to thrive, cerebral palsy, and attention deficit disorder (ADD). Differences in clinical disease specific to allelic variants have not been documented. Factors that may increase risk for disease onset or modify disease severity are age when the first episode occurred, fasting, and presence of infection. Acute attacks must be treated immediately with appropriate intravenous doses of glucose. For those diagnosed, long-term management of the disease includes preventing stress caused by fasting and maintaining a high-carbohydrate, reduced-fat diet, and carnitine supplementation. Hospitalization costs attributable to morbidity and mortality from MCADD are unknown; MCADD is not a diagnosis in the International Classification of Disease, 10th Revision (ICD-10) codebook. Furthermore, the penetrance of the MCAD genotypes is unknown; there appears to be a substantial number of asymptomatic MCADD individuals and some uncertainty regarding which individuals will manifest symptoms and which individuals will remain asymptomatic. Several technologies are available to detect MCADD. Diagnostic technologies include DNA-based tests for K304E mutations using the polymerase chain reaction (PCR), and the detection of abnormal metabolites in urine. Screening technologies include tandem mass spectrometry (MS/MS), which detects abnormal metabolites mostly in blood. State programs are beginning to offer screening in newborns for MCADD using MS/MS. In addition, a private company currently offers voluntary supplemental newborn screening for MCADD to birthing centers.

Acyl-CoA Dehydrogenases↗
PubMedDate not supplied

Neonatal neurobehavioral characteristics as correlates of maternal alcohol use during gestation.

To determine the neurobehavioral consequences of alcohol use during different periods in gestation, we compared the behavior of 103 neonates born to women who: drank a mean of 12 ounces of absolute alcohol per week throughout pregnancy; drank a mean of 14 ounces of absolute alcohol and were otherwise comparable to the first group but stopped drinking in the second trimester, and never drank at all during pregnancy. Low socioeconomic status, predominantly black women applying for prenatal care at a large inner city hospital were recruited in the second trimester of pregnancy, and those reporting alcohol use were advised to stop drinking. Neurobehavioral evaluation with the Brazelton Neonatal Behavioral Assessment Scale was conducted at 3 days postnatal age. As a group, infants exposed to alcohol at any time during gestation were found to have significant alterations in reflexive behavior, less mature motor behavior, and an increased activity level in comparison to unexposed infants. Infants whose mothers stopped drinking in the second trimester were superior to those whose mothers continued to drink throughout pregnancy in observed state control, need for stimulation, motor tone, tremulousness, and asymmetries in reflexive behavior. These results indicate that characteristic damage does occur to the central nervous system of a fetus exposed to alcohol throughout pregnancy, and that exposure during only the early part of pregnancy also seems to have measurable effects. Multivariate analysis indicated that neither amount of alcohol used per week nor cigarette use contributed significantly to these effects on infant behavior.

Alcoholism↗
PubMedDate not supplied

Zinc and copper status of treated children with phenylketonuria.

Children with phenylketonuria (PKU) are treated with semi-synthetic diets restricted in phenylalanine. Low or phenylalanine-free formulae provide the majority of protein and energy in the diet while phenylalanine requirements are met by low-protein natural foods. Because of the restriction of natural protein sources in this diet, the study assessed the zinc and copper nutriture of treated children with PKU and correlated linear growth with zinc status. The plasma zinc of the PKU population was 66.6 +/- 3.3 micrograms/dl (mean +/- SEM). The hair zinc was 70.2 +/- 11.5 micrograms/g (mean +/- SEM). The mean plasma and hair zinc of the PKU population were significantly different (p less than 0.05) when compared to normal values of 84.2 +/- 2.9 micrograms/dl and 130.7 +/- 8.3 micrograms/g (mean +/- SEM), respectively. The dietary zinc intake of 10 PKU patients was 8.56 +/- 2.68 mg/day (mean +/- SD). No significant differences (p less than 0.123) were found when the mean zinc intake was compared with recommended dietary allowances for age of 10 mg/day. No significant correlations were found when plasma and hair zinc were plotted with height percentiles. Plasma copper of the PKU subjects (87.6 +/- 6.6 micrograms/dl, mean +/- SEM) was significantly less than that of normal young children (121.5 +/- 3.1 micrograms/dl, mean +/- SEM) despite a copper intake a 1.45 +/- 0.35 mg/day (mean +/- SD).

Child↗
PubMedDate not supplied

The effect of volume and duration of prenatal ethanol exposure on neonatal physical and behavioral development.

Recent research on the effects of alcohol use during pregnancy indicate that discontinuing alcohol use mid-pregnancy can prevent or minimize many of the adverse consequences usually observed in the children of women who consume alcohol throughout pregnancy. Few studies have examined the contributions of maternal dose level independent of the duration of drinking during pregnancy. In this study the effects of prenatal dose (volume of maternal alcohol use per week during pregnancy) and duration (exposure throughout pregnancy vs. exposure in the first and second trimesters only) on newborn physical and behavioral development were examined. Dependent measures were cluster scores on the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) at three days, infant birthweight, length, and head circumference. Subjects were infants of obstetric patients at Grady Memorial Hospital in Atlanta who were participating in a study on the effects of alcohol use during pregnancy on infant outcome (n = 149). Subjects were primarily black and of low socioeconomic status. Infants of women who continued to drink throughout pregnancy differed from those of women who did not drink during pregnancy on orientation, (the ability to attend to environmental stimuli), p less than 0.05, autonomic regulation, p less than 0.0002, birthweight, p less than 0.04, length, p less than 0.01, and head circumference, p less than 0.01. Both prenatal alcohol dose, p less than 0.03, and the duration of alcohol exposure, p less than 0.03, independently affected autonomic regulation. A significant interaction was found for birthweight, p less than 0.02, with independent main effects for both dose and duration of exposure, p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Child Behavior↗