Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy.

Niehues, R; Hasilik, Martin; Alton, Gordon; Körner, Christian; Schiebe-Sukumar, M.; Koch, Hans Georg; Zimmer, KP; Wu, Rongrong; Harms, E.; Reiter, Karl; Figura, Kurt Von; Freeze, Hudson H.; Harms, H. K.; Marquardt, Thorsten

doi:10.1172/jci2350

Cited by 405 publications

(387 citation statements)

References 19 publications

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“…Inadequate maternal or fetal nutrition could contribute additional environmental stress. Both mannose and fucose supplements have been used to treat CDG patients, 24,49,50 showing that these sugars can have a therapeutic effect. An inadequate supply can contribute to clinical phenotype in susceptible patients.…”

Section: Discussionmentioning

confidence: 99%

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Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia

Westphal

Peterson

Patterson

et al. 2001

Genetics in Medicine

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Purpose: Congenital disorders of glycosylation (CDG) result from mutations in N-glycan biosynthesis. Mutations in phosphomannomutase (PMM2) cause CDG-Ia. Here, we report four clinically mild patients and their mutations in PMM2. Methods: Analysis of the PMM2 cDNA and gene revealed the mutations affecting the glycosylation efficiency. Results: The patients have 30% to 50% normal PMM activity in fibroblasts due to different mutations in PMM2, and we studied the effect of each mutation on the PMM activity in a Saccharomyces cerevisiae expression system. Conclusions: Each patient carried a severe mutation that decreased the PMM activity to less than 10% as well as a relatively mild mutation. A new mutation, deletion of base 24, changed the reading frame. The C9Y, C241S, and L32R mutations showed 27% to 45% activity when expressed in the eukaryotic expression system, and the more severe D148N was shown to be thermolabile. Genet Med 2001:3(6):393-398.

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Section: Discussionmentioning

confidence: 99%

“…20,24 Sequence analysis of the cDNA and genomic DNA Extractions of total RNA and DNA, first-strand PCR, amplification, purification, and sequencing analysis of the PMM2 gene were done as described previously. 25 …”

Section: Radioactive Labelingmentioning

confidence: 99%

Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia

Westphal

Peterson

Patterson

et al. 2001

Genetics in Medicine

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“…9 More importantly, treatment with oral mannose supplementation appears to improve both the clinical and biochemical abnormalities. 5,10 Treatment with mannose was fortunately not started in this child while we awaited confirmation of his diagnosis, because the potential conversion of mannose to fructose could have caused more complications. Features not consistent with CDG Ib included the improvement in his clinical features without mannose supplementation.…”

Section: Case Discussionmentioning

confidence: 95%

A Six-month-old infant with liver steatosis

Stormon

Cutz²,

Furuya³

et al. 2004

The Journal of Pediatrics

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A6-month-old male infant was sent to a quaternary referral hospital from a tertiary referral hospital with a possible diagnosis of a fatty acid oxidation disorder. HISTORY OF PRESENTING ILLNESSThe infant was well until 4 weeks before admission at the quaternary referral hospital. He, along with the rest of his family, experienced an acute gastroenteritic illness with vomiting and watery diarrhea. Although his siblings and parents recovered, he did not, and because of concerns of a presumed secondary lactose intolerance he was changed from his usual Similac (Ross Products, Abbott Laboratories, Columbus, Oh) formula to a soy-based formula (Alsoy, Nestle Inc, Eau Claire, Wisc) about one week into his illness. He became more lethargic and hypotonic with persisting vomiting and diarrhea, and was admitted to a tertiary referral hospital. PAST HISTORYHe was born to nonconsanguineous parents of Italian (father) and Hungarian-French (mother) descent. He had two female siblings both of whom had been well in the past, and there was no family history of notable diseases. During pregnancy his mother had a laparoscopic cholecystectomy at 20 weeks' gestation, and he was born by Cesarean delivery at term because of fetal bradycardia. There were no other problems in the perinatal period. He had been well before this current illness, with appropriate growth parameters and development. He was fed a combination of breast milk and formula (Similac, Ross Pharmaceuticals). Cereals were introduced at 5 months along with other age-appropriate foods such as bananas and some vegetables. TERTIARY REFERRAL HOSPITALSymptoms of diarrhea and poor feeding had persisted for approximately two weeks before admission to the tertiary referral hospital, where he was found to be weak, floppy, and lethargic but easily rousable. He had massive hepatomegaly, with the liver edge palpable in the right iliac fossa, which had not been previously noted on several abdominal examinations. There was no splenomegaly, ascites, or signs of chronic liver disease. He was not clinically jaundiced despite elevated conjugated bilirubin. An Escherichia coli urinary tract infection (UTI) was Initial hematology and biochemical results are shown in Tables I and II. Of note is the presence of hypoglycemia, hypokalemia, hypophosphatemia, low plasma carnitine levels, hepatic dysfunction and coagulopathy. Other investigations that were normal included venous blood gas, plasma lactate, amino acids, creatine kinase, galactosemia screen, and routine urinalysis (ketones negative). Gas chromatography mass spectroscopy analysis of urinary organic acids showed elevated dicarboxylic acids with hypoketosis at the time of hypoglycemia. Urinary succinylacetone was negative. Serology for hepatitis viruses A, B, and C was negative. An echocardiogram demonstrated thickening of the interventricular septum, suggestive of a possible cardiomyopathy. An abdominal ultrasonogram showed an enlarged, heterogeneous liver with increased echogenicity and normal portal flow. A liver biopsy was performed ...

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“…The patients have a pathognomonic glycosylation deficiency in their serum transferrin (Andréasson et al 1992). The disease is most commonly caused by mutations in the gene for phosphomannomutase-2 (PMM2; CDG syndrome type 1a; Matthijs et al 1997) or less commonly in the gene for phosphomannose isomerase-1 (PMI1; CDG syndrome type 1b; Niehues et al 1998). The syndrome illustrates that generalized glycosylation defects can induce tapetoretinal degenerations, but the precise mechanism has not been established.…”

Section: Glycosylation Deficienciesmentioning

confidence: 99%

Tapetoretinal degenerations: Experiences, experiments and expectations

Ehinger

2000

Acta Ophthalmologica Scandinavica

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ABSTRACT. Tapetoretinal degenerations are a common cause for vision problems, but have until recently not been amenable to rational treatment. With rapidly increasing insights into basic neurobiology and pathobiology this has now begun to change. From having been a relatively small group of largely unknown yet fairly prevalent disorders, they are rapidly forming a large set of well defined diseases, and it is easy to predict that our knowledge about them will continue to increase for many years to come. Vitamin A (15 000 IU daily) is currently the only rational treatment available. However, in experimental animals, therapy strategies are now actively being developed along several different lines. Apoptotic photoreceptor cell death can be delayed with different drugs, and at least one of them, diltiazem, is approved for human use in cardiovascular diseases. It remains to be seen if it has any clinically significant effect in human tapetoretinal degenerations. Other strategies aim at counteracting the production of harmful protein variants, acting either on DNA or mRNA levels. Transgenes can also be used to induce the production of important but missing metabolic components. Finally, cells or retina sheets can be transplanted, either to replace failing cells or as a source for missing trophic factors. Neither of these strategies has yet been transferred to humans, but trials are under way. With the high increase in the flow of new information on tapetoretinal disorders, much more precise diagnoses and much improved treatments are soon to be expected, augmenting considerably the possibilities for ophthalmologists to help patients with such diseases. It is not likely that there will be a single treatment for all the many varieties. Instead, we are most likely going to see pharmacological treatments for some of them, DNA transfers for some, and transplantations for others.

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Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy.

Cited by 405 publications

References 19 publications

Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia

Functional significance of PMM2 mutations in mildly affected patients with congenital disorders of glycosylation Ia

A Six-month-old infant with liver steatosis

Tapetoretinal degenerations: Experiences, experiments and expectations

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