Clinical and biochemical heterogeneity between patients with glycogen storage disease type IA: the added value of CUSUM for metabolic control

Fabian Peeks, Thomas A. H. Steunenberg, Foekje de Boer, M. Estela Rubio-Gozalbo, Monique Williams, Rob Burghard, Fabienne Rajas, Maaike H. Oosterveer, David A. Weinstein, Terry G. J. Derks*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Web of Science)

Abstract

Objective To study heterogeneity between patients with glycogen storage disease type Ia (GSD Ia), a rare inherited disorder of carbohydrate metabolism caused by the deficiency of glucose-6-phosphatase (G6Pase).

Study design Descriptive retrospective study of longitudinal clinical and biochemical data and long- term complications in 20 GSD Ia patients. We included 11 patients with homozygous G6PC mutations and siblings from four families carrying identical G6PC genotypes. To display subtle variations for repeated triglyceride measurements with respect to time for individual patients, CUSUM-analysis graphs were constructed.

Results Patients with different homozygous G6PC mutations showed important differences in height, BMI, and biochemical parameters (i.e., lactate, uric acid, triglyceride, and cholesterol concentrations). Furthermore, CUSUM-analysis predicts and displays subtle changes in longitudinal blood triglyceride concentrations. Siblings in families also displayed important differences in biochemical parameters (i.e., lactate, uric acid, triglycerides, and cholesterol concentrations) and long-term complications (i.e., liver adenomas, nephropathy, and osteopenia/osteoporosis).

Conclusions Differences between GSD Ia patients reflect large clinical and biochemical heterogeneity. Heterogeneity between GSD Ia patients with homozygous G6PC mutations indicate an important role of the G6PC genotype/mutations. Differences between affected siblings suggest an additional role (genetic and/or environmental) of modifying factors defining the GSD Ia phenotype. CUSUM-analysis can facilitate single-patient monitoring of metabolic control and future application of this method may improve precision medicine for patients both with GSD and remaining inherited metabolic diseases.

Original languageEnglish
Pages (from-to)695-702
Number of pages8
JournalJournal of Inherited Metabolic Disease
Volume40
Issue number5
DOIs
Publication statusPublished - Sep 2017

Keywords

  • CUSUM
  • ESGSDI
  • GSD Ia
  • G6PC
  • Heterogeneity
  • Modifying factors
  • GLUCOSE-6-PHOSPHATASE GENE
  • GLUCOSE-PRODUCTION
  • G6PC GENE
  • MUTATIONS
  • 1A
  • INFANCY

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