Bij de à terme neonaat is asfyxie de meest frequente oorzaak van neonatale convulsies. Om de diagnose asfyxie te kunnen stellen, moet worden voldaan aan een specifiek klinisch beloop, specifieke laboratoriumafwijkingen en specifieke beeldvorming. Is dit niet het geval dan is de differentiaaldiagnose breed en aanvullend onderzoek uitgebreid. Het gepresenteerde diagnostisch stappenplan kan hierbij een leidraad zijn. Door middel van basisevaluatie worden eerst behandelbare en frequent voorkomende oorzaken aangetoond c.q. uitgesloten, zodat eventuele gerichte therapie kan plaatsvinden. Levert dit geen oorzaak op dan is een uitgebreide evaluatie naar zeldzamere aandoeningen geïndiceerd.

We describe a 16-year old boy with glycogen storage disease type Ib, homozygous for the common 1211-1212delCT mutation, who never experienced neutropenia, and did not suffer from frequent infections or inflammatory bowel disease. In addition, neutrophil function tests showed no abnormalities.

We present a relatively mild case of peroxisomal D-bifunctional protein deficiency with inconsistent screening results in plasma for peroxisomal disorders.

MR spectroscopy results in a mild case of guanidinoacetate methyltransferase (GAMT) deficiency are presented. The approach differs from previous MRS studies in the acquisition of a chemical shift imaging spectral map showing gray and white matter with the corresponding spectra in one overview. MR spectroscopy revealed guanidinoacetate (GAA) in the absence of creatine. New is that GAA signals are more prominent in gray matter than in white. In the prevailing view, that enzyme deficiency is localized in liver and pancreas and that all GAA is transported into the brain from the blood and the cerebrospinal fluid, this would be compatible with a more limited uptake and/or better clearance of GAA from the white matter compared to the grey matter.

Summary: Growth retardation is one of the clinical characteristics of glycogen storage disease (GSD) type IX. Initial growth retardation has been described in a few case reports, followed by a complete catch-up in growth. This study aimed to determine the growth pattern of patients with GSD IX. Growth charts of 51 male Dutch patients with GSD IX (age 0–33 years, median follow-up time 8.3 years (range 0–30.5 years)) were studied retrospectively and compared with Dutch standard growth charts. Patients had a normal height at birth, significant growth retardation between the ages of 2 and 10 years (mean z-score −1.96), delayed growth spurt in puberty and catch-up towards quite normal final height (mean z-score −0.55). We conclude that GSD IX patients have a specific growth pattern characterized by initial growth retardation, a late growth spurt and complete catch-up in final height. Intervention for growth retardation is therefore ingeneral not warranted. It is speculated that mild hypoglycaemia related to the disorder may cause endocrine changes. Because the glucose need per kg bodyweight decreases with age, the enzyme defect becomes less important with ageing and the effect on growth diminishes.

Glycogen storage disease type 1b (GSD1b) is a rare autosomal recessive disorder characterized by hypoglycemia, hepatomegaly, and growth retardation, and associated-for unknown reasons- with neutropenia and neutrophil dysfunction. In 5 GSD1b patients in whom nicotin-amide adenine dinucleotide phosphate-oxidase activity and chemotaxis were defective, we found that the majority of circulating granulocytes bound Annexin-V. The neutrophils showed signs of apoptosis with increased caspase activity, condensed nuclei, and perinuclear clustering of mitochondria to which the proapoptotic Bcl-2 member Bax had translocated already. Granulocyte colony-stimulating factor (G-CSF) addition to in vitro cultures did not rescue the GSD1b neutrophils from apoptosis as occurs with G-CSF-treated control neutrophils. Moreover, the 2 GSD1b patients on G-CSF treatment did not show significantly lower levels of apoptotic neutrophils in the bloodstream. Current understanding of neutrophil apoptosis and the accompanying functional demise suggests that GSD1b granulocytes are dysfunctional because they are apoptotic.

The occurrence of (symptoms related to) osteopenia is a known complication in glycogen storage disease type Ia (GSD Ia) patients. However, only limited information is available about bone mineral density (BMD). Using dual energy x-ray absorptiometry, we studied both cross-sectional and longitudinal lumbar spine areal BMD (BMDareal in g/cm2), areal BMD corrected for delayed bone maturation (BMDbone age in g/cm2), and volumetric BMD (BMDvol in g/cm3). Prepubertal GSD Ia patients (n = 8) had normal BMD (median z-scores BMDareal -0.6, BMDbone age -0.5 and BMDvol - 0.5), whereas adolescent patients (n = 12) and adult patients (n = 9) had significantly reduced BMD (BMDareal -2.3, BMDbone age -1.6, BMDvol -2.0, and BMDareal -1.9, BMDvol-1.5, respectively). Our longitudinal study, showing a stable BMDareal but a trend to a decrease in BMDvol in prepubertal patients during follow-up, did not clarify whether the difference in BMD between prepubertal and adolescent/adult patients reflects a diminished accretion of BMD during childhood or reflects historica l differences in treatment. In adolescent and adult GSD Ia patients, BMDareal and BMDvol were reduced but stable during follow-up. Especially patients with delayed bone maturation were at risk for reduced BMD. No correlation between parameters of metabolic control and BMD could be detected. Daily calcium intake was within recommended allowances ranges. Abnormal biochemical results included hypomagnesaemia (29%), hypercalciuria (34%) and reduced tubular resorption of phosphate (21%).Although the underlying pathophysiology of reduced BMD in GSD Ia remains unsolved, metabolic control should be optimized to correct as much as possible metabolic and endocrine abnormalitie s that may influence both bone matrix formation and bone mineral accretion.

We describe 2 patients with glycogen storage disease type 1a and severe hyperlipidemia without premature atherosclerosis. Susceptibility of low-density lipoproteins to oxidation was decreased, possibly related to the ~40-fold increase in palmitate synthesis altering lipoprotein saturated fatty acid contents. These findings are potentially relevant for antihyperlipidemic treatment in patients with glycogen storage disease type 1a.

Glycogen storage disease type I (GSD I) (McKusick 232200) is caused by inherited defects of the glucose-6-phosphatase complex. Patients with GSD Ia as well as patients with GSD Ib may suffer from intermittent diarrhoea, which seems to worsen with age. The cause of this diarrhoea is unknown. This study describes the results of investigations of intestinal functions and morphology in patients with GSD Ia and GSD Ib, which were performed to detect a common cause for chronic diarrhoea in GSD I. The following were investigated: faecal fat excretion, faecal α1-antitrypsin and faecal chymotrypsin, expiratory H2 concentrations, persorption of cornstarch in urine and colonic biopsies. With the investigations presented in this study, no common cause for diarrhoea in GSD I was found. In GSD Ib loss of mucosal barrier function due to inflammation, documented by increased faecal α1-antitrypsin excretion (3.5–9.6 mg/g dry faeces) and inflammation in the colonic biopsies, seems to be the main cause. The inflammation is most likely related to disturbed neutrophil function, which is often found in GSD Ib. Whether another cause is involved in GSD Ia and in GSD Ib, related to the disturbed function of glucose-6-phosphatase in the enterocyte, remains to be investigated.

OBJECTIVE:To investigate the incidence, the severity, and the course of neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in glycogen storage disease (GSD) type Ib.METHOD:As part of a collaborative European Study on GSD type I, a retrospective registry was established in 12 European countries that included all patients with GSD-I who were known at the centers and were born from 1960 to 1995. Of a total of 288 patients with GSD-I, 57 who had GSD-Ib form the basis of this study.RESULTS:Neutropenia (defined as an absolute neutrophil count <1 x 10(9)/L) was found in 54 patients. In 64% of the patients neutropenia was documented before the age of 1 year, but in 18% of the patients neutropenia was first noted between the ages of 6 and 9 years. Neutropenia was persistent in 5 patients and intermittent without any clear cyclical course in 45. Neutrophil function was investigated in 18 patients with neutropenia and was abnormal in all. Perioral infections were reported in 37 patients, perianal infections in 27 patients, and protracted diarrhea in 23 patients. Findings on colonoscopy and radiologic studies in 10 of 20 patients suspected to have IBD were abnormal in all. All patients with IBD, perioral infections, and perianal infections had neutropenia.CONCLUSIONS:Intermittent severe neutropenia is frequently found in patients with GSD-Ib. The study also indicates that IBD in GSD-Ib is underdiagnosed; up to 77% of the patients studied had evidence of IBD, all of whom had neutropenia. IBD was not detected in those with normal neutrophil counts. These findings support the notion that neutropenia and/or neutrophil dysfunction in GSD-Ib and IBD are causally related.

Bandsma, R. H.J.; Rake, J. P.; Ubels, F.; Princen, H. M.G.; Neese, R. A.; Hellerstein, M. K.; Smit, P. G.A.; Kuipers, F. Author Information

Deficient activity of glucose-6-phosphatase (G6Pase) causes glycogen storage disease type Ia (GSD Ia). We analysed the G6Pase gene of 16 GSD Ia patients using single strand conformation polymorphism (SSCP) analysis prior to automated sequencing of exon(s) revealing an aberrant SSCP pattern. In all GSD Ia patients we were able to identify mutations on both alleles of the G6Pase gene, indicating that this method is a reliable procedure to identify mutations. Four novel mutations (175delGG, R170X, G266V and V338F) were identified.

Journal of Inherited Metabolic DiseaseVolume 21, Issue 3 p. 227-231 Article Neutropenia and neutrophil dysfunction in glycogen storage disease type 1c G. Visser, G. VisserSearch for more papers by this authorJ. Herwig, J. HerwigSearch for more papers by this authorJ. P. Rake, J. P. RakeSearch for more papers by this authorK. E. Niezen-Koning, K. E. Niezen-KoningSearch for more papers by this authorA. J. Verhoeven, A. J. VerhoevenSearch for more papers by this authorG. P. A. Smit, G. P. A. SmitSearch for more papers by this author G. Visser, G. VisserSearch for more papers by this authorJ. Herwig, J. HerwigSearch for more papers by this authorJ. P. Rake, J. P. RakeSearch for more papers by this authorK. E. Niezen-Koning, K. E. Niezen-KoningSearch for more papers by this authorA. J. Verhoeven, A. J. VerhoevenSearch for more papers by this authorG. P. A. Smit, G. P. A. SmitSearch for more papers by this author First published: 01 June 1998 https://doi.org/10.1023/A:1005399602020Citations: 14AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume21, Issue3June 1998Pages 227-231 RelatedInformation