CYSTIC FIBROSIS OF THE PANCREAS

103 individuals from 16 families with cystic fibrosis and 87 individuals without family history of cystic fibrosis have been studied using the methods of cell culture. Skin fibroblast cultures derived from 19 affected children, and fibroblast cultures from 11 different organs obtained at autopsy from two affected children, showed cellular metachromasia. The morphological appearance and the intracellular mucopolysaccharide content enabled these cultures to be divided into two distinct classes. Class I had discrete cytoplasmic metachromatic vesicles and a mucopolysaccharide content similar to that observed in normal fibroblasts. In class II the metachromasia was present in both vesicles and granules and was evenly distributed throughout the cytoplasm. The mucopolysaccharide content of these cells was markedly increased. The cultures derived from the parents, presumed heterozygotes, and other members of each family showed cells with the same type of metachromasia as that demonstrated by the propositus. These data strongly suggest that cystic fibrosis is not a homogeneous entity and, moreover, can be caused by homozygosity of genes at two distinct loci. The recognition of cytoplasmic abnormalities in skin fibroblasts derived from affected individuals and heterozygous carriers for cystic fibrosis should facilitate genetic and biochemical studies on the heterogeneity of this inborn error of metabolism.

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RNA Methylation—A Possible Genetic Marker in Cystic Fibrosis

PEDIATRICS ◽

10.1542/peds.50.3.485 ◽

1972 ◽

Vol 50 (3) ◽

pp. 485-487

Author(s):

Owen M. Rennert ◽

Richard L. Julius ◽

David LaPointe

Keyword(s):

Cystic Fibrosis ◽

Cell Culture ◽

Genetic Marker ◽

Inborn Error ◽

Cultured Cells ◽

Inborn Error Of Metabolism ◽

Initial Report ◽

Rna Methylation ◽

Basic Defect ◽

Cell Culture Systems

Cystic fibrosis (CF) of the pancreas was initially thought to be an inborn error of metabolism affecting only exocrine tissue. In 1969, the demonstration by Danes and Bearn1 of metachromasia in cultivated fibroblasts obtained from patients with CF gave experimental support to the hypothesis that all CF cells reflect the basic biochemical defect. After this initial report several investigators observed that tissue cultured cells from some patients with CF and heterozygotes accumulated increased quantities of acid mucopolysaccharides and glycogen. No basic defect in these cell culture systems has been identified. No definitive test for the detection of the heterozygote state is available. See table in the PDF file

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Albumin in the Meconium of Infants with Cystic Fibrosis: A Preliminary Report

PEDIATRICS ◽

10.1542/peds.33.1.115 ◽

1964 ◽

Vol 33 (1) ◽

pp. 115-119

Author(s):

WILMER C. WISER ◽

FRANCES R. BEIER

Keyword(s):

Cystic Fibrosis ◽

Family History ◽

Protein Content ◽

Preliminary Report ◽

Diagnostic Procedure ◽

Serum Proteins ◽

Newborn Infants ◽

Control Group ◽

Abnormal Protein ◽

History Of

Meconium samples were collected from 5 newborn infants, who had a known family history of cystic fibrosis of the pancreas but who did not present with meconium ileus, and 11 normal newborn infants. Extracts of the meconium samples were examined for the presence of serum proteins by paper and immunoelectrophoresis. Three of the infants who had a family history of cystic fibrosis of the pancreas showed protein in their meconium, and this was identified by immunoelectrophoresis as consisting mainly of albumin; each of these babies subsequently developed classic symptoms of cystic fibrosis of the pancreas. The two remaining infants had no albumin in the meconium and did not develop signs of cystic fibrosis. None of the meconium samples of the control group of infants contained detectable amounts of albumin. Possible sources of the abnormal protein content of meconium are discussed, and the suggestion that the finding of albumin in meconium of newborn infants may prove to constitute a valuable diagnostic procedure for screening newborn infants for cystic fibrosis of the pancreas is advanced.

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Galactokinase deficiency: a treatable cause of bilateral cataracts

BMJ Case Reports ◽

10.1136/bcr-2021-242227 ◽

2021 ◽

Vol 14 (6) ◽

pp. e242227

Author(s):

Catarina Cordeiro ◽

Paula Garcia ◽

Dalila Coelho ◽

Mónica Oliva

Keyword(s):

Differential Diagnosis ◽

Family History ◽

Physical Examination ◽

Congenital Cataract ◽

Genetic Variant ◽

Metabolic Diseases ◽

Systemic Diseases ◽

Galactose Metabolism ◽

Biochemical Studies ◽

History Of

Congenital cataract can be caused by several systemic diseases and differential diagnosis should be done between infections, genetic or metabolic diseases. We present a case of a 12-month-old girl with bilateral nuclear cataracts that was referred for investigation. Since she did not present a family history of congenital cataracts or metabolic diseases, and her physical examination was normal, a systemic evaluation was performed. Biochemical studies disclosed abnormal galactose metabolism signs. The diagnosis of galactokinase (GALK1) deficiency was considered and the study of the GALK1 gene allowed identifying a pathogenic genetic variant and a predictably pathogenic missense mutation, previously not described. Dietary measures were imposed with a good evolution.

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Defect in Dimethylglycine Dehydrogenase, a New Inborn Error of Metabolism: NMR Spectroscopy Study

Clinical Chemistry ◽

10.1093/clinchem/45.4.459 ◽

1999 ◽

Vol 45 (4) ◽

pp. 459-464 ◽

Cited By ~ 56

Author(s):

Sytske H Moolenaar ◽

Jo Poggi-Bach ◽

Udo FH Engelke ◽

Jacqueline MB Corstiaensen ◽

Arend Heerschap ◽

...

Keyword(s):

Nmr Spectroscopy ◽

1H Nmr ◽

Inborn Error ◽

1H Nmr Spectroscopy ◽

13C Nmr Spectroscopy ◽

Inborn Error Of Metabolism ◽

Gas Chromatography Mass Spectrometry ◽

High Concentration ◽

History Of

Abstract Background: A38-year-old man presented with a history of fish odor (since age 5) and unusual muscle fatigue with increased serum creatine kinase. Our aim was to identify the metabolic error in this new condition. Methods: We used 1H NMR spectroscopy to study serum and urine from the patient. Results: The concentration of N,N-dimethylglycine (DMG) was increased ∼100-fold in the serum and ∼20-fold in the urine. The presence of DMG as a storage product was confirmed by use of 13C NMR spectroscopy and gas chromatography–mass spectrometry. The high concentration of DMG was caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGDH). A homozygous missense mutation was found in the DMGDH gene of the patient. Conclusions: DMGDH deficiency must be added to the differential diagnosis of patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro 1H NMR spectroscopy of body fluids.

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Language Onset and Concomitant Speech and Language Problems in Subgroups of Stutterers and Their Siblings

Journal of Speech Language and Hearing Research ◽

10.1044/jshr.2504.482 ◽

1982 ◽

Vol 25 (4) ◽

pp. 482-486 ◽

Cited By ~ 12

Author(s):

Robin A. Seider ◽

Keith L. Gladstien ◽

Kenneth K. Kidd

Keyword(s):

Family History ◽

Same Sex ◽

Speech And Language ◽

Negative Family History ◽

Late Talkers ◽

Language Problems ◽

History Of ◽

Language Onset

Time of language onset and frequencies of speech and language problems were examined in stutterers and their nonstuttering siblings. These families were grouped according to six characteristics of the index stutterer: sex, recovery or persistence of stuttering, and positive or negative family history of stuttering. Stutterers and their nonstuttering same-sex siblings were found to be distributed identically in early, average, and late categories of language onset. Comparisons of six subgroups of stutterers and their respective nonstuttering siblings showed no significant differences in the number of their reported articulation problems. Stutterers who were reported to be late talkers did not differ from their nonstuttering siblings in the frequency of their articulation problems, but these two groups had significantly higher frequencies of articulation problems than did stutterers who were early or average talkers and their siblings.

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