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Biomedical subjects

R Gitzelmann

Publications and source records attributed to R Gitzelmann.

At least 91 records · Page 5Linked to original sources
PubMed1980

[Decompensated liver cirrhosis caused by galactosemia in a 52-year-old man].

A 52-year-old oligophrenic man hospitalized for esophageal hemorrhage had histologically proven liver cirrhosis and died from massive rehemorrhage. As a neonate he had survived severe jaundice, had had delayed psychomotor development and remained severely retarded. At age 15 years, bilateral cataracts had been excised and from 18 to 25 years he had had occasional grand mal seizures. The triad oligophrenia, liver cirrhosis and cataracts, prompted suspicion of galactosemia. Deficiency of galactose-1-phosphate uridyltransferase was demonstrated in blood and post mortem tissue. At autopsy, liver cirrhosis and esophageal varices were confirmed and unilateral chronic pyelonephritis, bilateral nephrolithiasis and testicular atrophy were found. There was not brain pathology. The patient appeared to be the oldest nondiagnosed galactosemic and the first male patient in whom hypogonadism was documented.

Galactosemias↗
PubMed1980

Glycogenosis type I (glucose 6-phosphatase deficiency): I. Ultrastructural morphometric analysis of juvenile liver cells.

The essential biochemical characteristic of von Gierke's disease is an inborn glucose-6-phosphatase deficiency and glycogen storage in the liver and kidney. This expresses itself morphometrically as an increased volume of glycogen per unit volume of the hepatocellular cytoplasm. Since glucose-6-phosphatase activity in patients studied is practically at the zero level, and the endoplasmic reticulum loses a large part of its membrane values, we conclude that the remaining endoplasmic reticulum represents glucose-6-phosphatase free membranes. A typical structural feature of the endoplasmic reticulum in von Gieke's disease is the appearance of "double contoured vesicles" (= pockets). These vesicles comprise approximately 3,5% of the total membrane system. The mitochondria play an important role in glycolysis and glycogen synthesis. It is thus to be expected that these organelles change in terms of their morphometric parameters in the course of glycogenosis type I. An important point in this direction is numerical mitochondrion reduction in combination with an unchanged mitochondrial volume.

Child, Preschool↗
PubMed1980

Excretion of pterins in phenylketonuria and phenylketonuria variants.

Total urinary biopterin (B), neopterin (Ne) and monapterin (M) were measured in 25 healthy newborns, children and adults, in 49 patients with phenylketonuria (PKU) assumed to be deficient in phenylalanine-4-hydroxylase (PH), in 7 patients with dihydrobiopterin synthetase (DHBS) deficiency and in 4 patients with dihydropteridine reductase (DHPR) deficiency. Excretion of Ne based on creatinine (Ne/C) was 6.6 times higher in healthy newborns than in adults, suggesting a slow maturation of DHBS activity. Newborns excreted more Ne than B and adults more B than Ne (32 and 72% B of the sum of B + Ne, respectively). In all cases, excretion of M was 4-15% of that of Ne. PH deficient patients excreted more B and Ne than healthy controls and again, newborns more than older children. In individual patients, excretion of pterins correlated with phenylalanine (Phe) concentration in plasma; plasma Phe of different patients did not correlate well with excretion of pterins. In PKU variants with deficiency of tetrahydrobiopterin (BH4), extreme pterin patterns were observed: in DHBS- and DHPR-deficient patients, less than 3.5 and more than 81% B were found, respectively. All 30 samples from these patients investigated could be distinguished from those of PH-deficient patients and controls by a two-dimensional plot of % B versus B/C. Thus it seems likely that PKU variants due to BH4 deficiency could be detected early and differentiated by measurement of urinary B, Ne and C. This was exemplified already in one case. - In urine of patients with DHBS deficiency, high concentrations of 3'-hydroxysepiapterin were found in addition to Ne.

Adolescent↗
PubMed1979

Fetal and adult albumins are indistinguishable by immunological and physicochemical criteria.

The existence of a functionally immature fetal albumin has been postulated to explain the reduced ability of newborn plasma to bind bilirubin and various drugs. In support of this, cord and adult albumin, isolated by a simple salting-out technique, were reported to differ in electrophoretic and chromatographic properties and in their resistance to alkali and proteolytic enzymes. However, the interpretation of these findings has since been questioned. To resolve this controversy, we have purified to homogeneity human serum albumins from pooled umbilical cord and adult donor plasma. The two albumins were compared and found to be indistinguishable by polyacrylamide gel electrophoresis with and without sodium dodecyl sulfate, as well as by immunoelectrophoresis and double immunodiffusion using specific antibodies against both albumins. Furthermore, the amino acid compositions, the aminoterminal sequence (Asp-Ala-His-Lys-Ser-Glu-Val-Ala-), the carboxy terminus (Leu), and the peptide fingerprints were identical in the two albumins. No significant differences were found by circular dichroism in the ultraviolet (200-350 nm). Binding studies with bilirubin showed association constants of 3.7 +/- 0.7 x 10(7) M(-1) for cord and 2.9 +/- 0.3 x 10(7) M(-1) for adult albumin, respectively. The circular dichroic spectra of 1:1 bilirubin.albumin complexes showed considerable variation between the batches but were not significantly different. The only difference was found in the fluorescence spectra of the bilirubin.albumin complexes, in which complexes with adult albumin showed only 75% of the relative fluorescence exhibited with cord albumin. The combined results nevertheless strongly indicate that fetal and adult albumins are very similar, if not identical.

Amino Acid Sequence↗
PubMed1979

Skin and bone lesions (dermato-osteolathyrism), possible side effects of D-penicillamine treatment, in a boy with cystinuria.

A 2 1/4 year-old boy was treated for cystinuria and urolithiasis with high fluid intake, sodium bicarbonate, and D-penicillamine, over a period of 5 3/4 years, unauthorized interruptions and prescribed pauses included. Therapy was partially sucessful but regrowth of calculi coincided with interruptions of D-penicillamine administration and also with the institution of a low-dose D-penicillamine regime. Flat feet, scoliosis, pectus carinatum, hypermobility of joints, molluscoid pseudotumors and atrophic scars were alarming side effects of D-penicillamine. However, the possibility was not excluded that a forme fruste of an Ehlers-Danlos syndrome preexisted in this boy and was effected by D-penicillamine. Only the molluscoid pseudotumors regressed when D-penicillamine was reduced or omitted temporarily. Osteolathyrism caused by D-penicillamine has hitherto not been reported in man.

Atrophy↗
PubMed1979

Abnormal collagen fibril structure in the gravis form (type I) of Ehlers-Danlos syndrome.

The Ehlers-Danlos syndrome (EDS) is a clinically, genetically, and biochemically heterogeneous group of disorders characterized by generalized connective tissue abnormalities. We studied collagen fibrils by electron microscopy in the dermis of nine individuals with clinical findings consistent with type I Ehlers-Danlos syndrome. In all patients the collagen fibrils had an increased mean diameter (13 to 40%) and showed a higher degree of variability in width and shape than collagen fibrils from controls. Approximately 5% of the fibrils were much wider (up to 500 nm. versus 90 nm.), had a highly irregular outline when viewed in cross-section, and were spiraled and fragmented in longitudinal view. The periodicity of banding was normal. The mode of inheritance was dominant in five patients, probably recessive in two, and could not be determined in the remaining two. Despite genetic heterogeneity among these patients with type I Ehlers-Danlos syndrome, the ultrastructural findings are indistinguishable and do not allow discrimination in sporadic cases between the recessive and the more common dominant form. We conclude that abnormalities of fibrillogenesis are heterogeneous in origin; some might be due to primary defects in collagen whereas others may result from alterations of noncollagenous extracellular matrix components that influence collagen fibril formation.

Adolescent↗
PubMed1979

Strychnine treatment attempted in newborn twins with severe nonketotic hyperglycinemia.

Strychnine, a potent antagonist of glycine was given to twins suffering from nonketotic hyperglycinemia at age 73 hours. Within hours of the onset of treatment favorable effects were observed such as improvements of muscle tone, movements, defense reactions, and probably breathing. Pyridoxine, N5-formyl-tetrahydrofolate and lipoic acid were given concomitantly with strychnine but failed to alter glycine levels in plasma and cerebrospinal fluid. The therapeutic trial was terminated after 2 1/2 days because success, though considerable, was judged inadequate.

Diseases in Twins↗
PubMed1979

Nutritive value of N-acetyl-L-tryptophan in man.

The nutritive value of N-acetyl-L-tryptophan was investigated by loading tests with deuterated L-tryptophan and deuterated N-acetyl-L-tryptophan in three healthy adults, and by a 7 day-long feeding experiment with deuterated N-acetyl-L-tryptophan in one healthy adult. After loading with deuterated N-acetyl-L-tryptophan, serum levels of deuterated tryptophan and kynurenine were only about 10%, and the amounts of deuterated 5-hydroxyindole-3-acetic acid excreted in 24 h approximately 30% of those found after deuterated tryptophan loading. During the feeding experiment with deuterated N-acetyl-L-tryptophan, the serum level of deuterated tryptophan remained below 20% of total serum tryptophan, and serum protein fell below the normal range. It is concluded that the nutritive value of N-acetyl-L-tryptophan is inferior to that of L-tryptophan. Contradictory findings of earlier studies are discussed.

Blood Proteins↗
PubMed1978

Unusually mild course of beta-glucuronidase deficiency in two brothers (mucopolysaccharidosis VII).

Two brothers with oligosymptomatic mucopolysaccharidosis VII were observed from age 11 8/12 to 16 years, and 15 1/2 to 19 years, respectively. Asymptomatic thoracic kyphosis and mild scoliosis were the prominent clinical features. Herniae, hepatosplenomegaly, corneal clouding and shortness of stature were absent. Both had Alder type granulations in polymorphonuclear leukocytes and to a lesser degree in monocytes. Ultrastructural analysis of blood leukocytes revealed polymorphous inclusions of probably more than one class of organic substances. Radiological signs were mild, confined to the spine and consisted of irregularities of upper and lower vertebral plates, of vertebral flattening and some osteophytic changes. Both patients excreted excessive amounts of acid mucopolysaccharides in urine and also globoside. Cultured skin fibroblasts of both patients contained metachromatic granules, had only approx. 10% of normal beta-glucuronidase activity and degraded sulfated mucopolysaccharides at a slower than normal rate. Sera of the patients had none or minimal beta-glucuronidase activity, the mother's serum had subnormal and the father's serum low-normal activity. The older brother is the oldest known case of mucopolysaccharidosis VII. As this hereditary disorder may take a remarkably mild clinical course, beta-glucuronidase-deficient juveniles may exist undetected in the general population.

Adolescent↗
PubMed1978

Nonketotic hyperglycinemia treated with strychnine, a glycine receptor antagonist.

A 6 1/2-month-old boy suffering from nonketotic hyperglycinemia has been treated for at least 12 months with oral strychnine. The drug caused improvement of muscle tone, motoricity, vigilance and social behavior. Glycine is one of the putative neurotransmitters of postsynaptic inhibition, particularly at the spinal and reticular levels, strychnine its antagonist at the postsynaptic membrane. Strychnine improved the patient's motoricity presumably by blocking the excessive glycine-mediated inhibition of motoneurons. The beneficial effect of strychnine on vigilance and social behavior is more difficult to explain but may have been related to its antagonism of glycine inhibition of brainstem reticular neurons.

Amino Acid Metabolism, Inborn Errors↗
PubMed1978

Hereditary fructose intolerance in early childhood: a major diagnostic challenge. Survey of 20 symptomatic cases.

Twenty infants and young children with hereditary fructose intolerance (HFI) were admitted to hospital. None was diagnosed at admission. Referals were for vomiting of unknown aetiology (16X), pyloric stenosis or hiatus hernia (5X), toxic condition (3X), and hepatomegaly of unknown origin (5X). Feeding difficulties (20X), vomiting (18X), and failure to thrive (16X) were leading symptoms. The most frequent clinical findings were hepatomegaly (18X), pallor (14X), haemorrhages (13X). Ascites, oliguria, tachypnoea, fever, splenomegaly and rickets were less frequent. Laboratory findings were indicative of disturbed hepatic and renal tubular function and also of disturbed intermediary metabolism (hypokaliaemia, hypophosphataemia). However, hypoglycaemia was found in only 4 out of 15 patients tested. Differential diagnosis after hospital admission centered on metabolic disorders such as glycogenoses, galactosaemia, tyrosinosis, or Wilson's disease. Hepatitis, toxic hepatosis, liver tumour, intrauterine infection and sepsis were also considered. Eleven children had first ingested fructose within the first 6 weeks of life. The diagnosis was usually established only many weeks or months after first fructose intake and appearance of symptoms. This documents how difficult the diagnosis of this disease can be both in practice and in hospital. The course was severe in 11 children and lethal in 4. In only 5 patients was the course mild. The 16 survivors are doing well under fructose-exclusion diet. Irreversible visual impairment after intraocular haemorrhage occurred once. In each case HFI could have been suspected immediately, had a detailed nutritional history been taken. Practising paediatricians should know the composition of commonly used infant formulae. They should never prescribe sugared condensed milk for intractable vomiting prior to excluding HFI. Solution for intravenous infusion containing fructose and sorbitol are life-threatening for undiagnosed HFI patients.

Age Factors↗
PubMed1977

The brush border membrane in hereditary sucrase-isomaltase deficiency: abnormal protein pattern and presence of immunoreactive enzyme.

In a child with hereditary sucrase-isomaltase deficiency immunoreactive enzyme was present in the intact duodenal mucosa. Polyacrylamide gel electrophoresis carried out with membrane fragments of an intestinal biopsy showed an abnormal protein band without enzyme activity. The mucosa had a relatively high residual isomaltase activity which was recovered from the gel in a position suggesting higher than normal molecular weight. The results indicated that in this patient the primary structural defect was in the sucrase moiety which was enzymatically inactive. The isomaltase subunits may have aggregated into a large molecular weight complex because of unavailability of their partners. The observation also provided evidence for separate biosynthesis of the two moieties of the sucrase-isomaltase complex.

Cell Membrane↗