Infantile Hyperchylomicronemia Due to A Novel GPIHBP1 Disease-Causing Variant Presenting with Milky Blood: A Rare Case Report

Authors

  • Iman Marzouq Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
  • Basant Elbanna Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
  • Sabine Schröder CENTOGENE GmbH, Rostock, Germany
  • Kornelia Tripolszki CENTOGENE GmbH, Rostock, Germany
  • Aida M. Bertoli-Avella CENTOGENE GmbH, Rostock, Germany
  • Aml Mahfouz Paediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

DOI:

https://doi.org/10.58427/apghn.2.2.2023.25-31

Keywords:

chylomicronemia, GPIHBP1, milky blood, medium-chain triglycerides, fenofibrates

Abstract

Background: Familial hyperchylomicronemia is a very rare autosomal recessive disorder and the most severe type of pediatric hyperlipidemia. The purpose of this case report is to enhance clinician's insight on the diagnosis and management plan in the case of infantile hyperchylomicronemia presenting with milky blood.

Case: We reported a 2-month-old infant with familial chylomicronemia syndrome. The patient was ‘accidentally’ diagnosed by the observation of milky blood. Exome sequencing revealed a homozygous likely pathogenic GPIHBP1 variant (NM_178172.5:c.193T>C p.(Cys65Arg)) confirming the diagnosis. He was treated with low-fat diet, a formula rich in medium-chain triglycerides and fenofibrates. After 4 days, his serum triglycerides decreased markedly. Fenofibrates were stopped at the age of one year and his serum triglycerides were maintained at low level with dietary measures. No complications occurred during two years follow-up period.

Discussion: Clinical manifestations of familial chylomicronemia syndrome start in early life with a very high level of hypertriglyceridemia and with monogenetic etiology, in contrast to multifactorial chylomicronemia syndrome that starts in adulthood, with proposed polygenic etiology. The main treatment of familial chylomicronemia syndrome is dietary fat restriction to less than 15% of the total caloric intake and medium-chain triglycerides which can bypass the chylomicron pathway of fat metabolism.

Conclusion: The main challenge in this case was the early diagnosis to protect the patient against serious complications. The mainstay of therapy is low-fat diet and medium-chain triglycerides. This case illustrates the relevance of establishing a timely genetic diagnosis and treatment.

References

Brahm AJ, Hegele RA. Chylomicronaemia--current diagnosis and future therapies. Nat Rev Endocrinol. 2015;11(6):352-62.https://doi.org/10.1038/nrendo.2015.26

Goldberg RB, Chait A. A Comprehensive Update on the Chylomicronemia Syndrome. Front Endocrinol (Lausanne). 2020;11:593931.https://doi.org/10.3389/fendo.2020.593931

Bain BJ, Bates I, Laffan MA. Dacie and lewis practical haematology e-book: Elsevier Health Sciences; 2016.

Rifai N. Tietz textbook of clinical chemistry and molecular diagnostics-e-book: Elsevier Health Sciences; 2017.

Trujillano D, Oprea GE, Schmitz Y, Bertoli-Avella AM, Abou Jamra R, Rolfs A. A comprehensive global genotype-phenotype database for rare diseases. Mol Genet Genomic Med. 2017;5(1):66-75.https://doi.org/10.1002/mgg3.262

Olivecrona G, Ehrenborg E, Semb H, Makoveichuk E, Lindberg A, Hayden MR, et al. Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia. J Lipid Res. 2010;51(6):1535-45.https://doi.org/10.1194/jlr.M002717

Franssen R, Young SG, Peelman F, Hertecant J, Sierts JA, Schimmel AW, et al. Chylomicronemia with low postheparin lipoprotein lipase levels in the setting of GPIHBP1 defects. Circ Cardiovasc Genet. 2010;3(2):169-78.https://doi.org/10.1161/circgenetics.109.908905

Jung MK, Jin J, Kim HO, Kwon A, Chae HW, Kang SJ, et al. A 1-month-old infant with chylomicronemia due to GPIHBP1 gene mutation treated by plasmapheresis. Ann Pediatr Endocrinol Metab. 2017;22(1):68-71.https://doi.org/10.6065/apem.2017.22.1.68

El-koofy NM, Abdo YA, El-Fayoumi D, Esmael AF, Elmonem MA, Ezzeldin Z. Management strategy and novel ophthalmological findings in neonatal severe hypertriglyceridemia: a case report and literature review. Lipids in Health and Disease. 2021;20(1):38.https://doi.org/10.1186/s12944-021-01464-2

El Idrissi Slitine N, Bennaoui F, Louachama O, Habibi L, Fdil N, Tali A, et al. Lipoprotein Lipase (LPL) Gene Mutation: A First Report in Children. International Journal of Pediatrics. 2017;5(10):5839-42.https://doi.org/10.22038/ijp.2017.25461.2163

Kuthiroly S, Yesodharan D, Radhakrishnan N, Ganapathy A, Mannan AU, Hoffmann MM, et al. Lipoprotein Lipase Deficiency. Indian J Pediatr. 2021;88(2):147-53.https://doi.org/10.1007/s12098-020-03305-z

Sustar U, Groselj U, Khan SA, Shafi S, Khan I, Kovac J, et al. A homozygous variant in the GPIHBP1 gene in a child with severe hypertriglyceridemia and a systematic literature review. Frontiers in Genetics. 2022;13.https://doi.org/10.3389/fgene.2022.983283

Wilson CJ, Priore Oliva C, Maggi F, Catapano AL, Calandra S. Apolipoprotein C-II deficiency presenting as a lipid encephalopathy in infancy. Ann Neurol. 2003;53(6):807-10.https://doi.org/10.1002/ana.10598

Aycan Z, Berberoğlu M, Ocal G, Altundas N, Adiyaman P, Evliyaoğlu O. Neonatal diabetes with hyperchylomicronemia. Indian J Pediatr. 2002;69(12):1087-9.https://doi.org/10.1007/bf02724395

Onci Es S, Lamzouri O, Bouchlarhem A, Haddar L, Mohammed A, mimouni H, et al. A very rare case of chylomicronemia revealed by cerebral thrombophlebitis in a 4-month-old infant. Ann Med Surg (Lond). 2022;75:103276.https://doi.org/10.1016/j.amsu.2022.103276

Millichap J. Apolipoprotein C-II Deficiency with Encephalopathy. Pediatric Neurology Briefs. 2003;17(7). https://doi.org/10.15844/pedneurbriefs-17-7-8

Rohrs HJ, Berger S. Pediatric lipid disorders in clinical practice. Medscape [Internet] Accessed. 2016;10

Published

2023-05-31

How to Cite

1.
Infantile Hyperchylomicronemia Due to A Novel GPIHBP1 Disease-Causing Variant Presenting with Milky Blood: A Rare Case Report. Arch Pediatr Gastr Hepatol Nutr [Internet]. 2023 May 31 [cited 2024 Dec. 3];2(2):25-31. Available from: https://apghn.com/index.php/journal/article/view/33