1 - Área de Pediatria Médica, Centro Hospital Universitário de Lisboa Central, Lisbon, Portugal;
2 - Unidade de Nutrição, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospital Universitário de Lisboa Central, Lisbon, Portugal;
3 - Unidade de I&D, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal;
4 - BioISI – Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal;
5 - Área de Pediatria Médica, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal;
- Poster no 17th International Symposium of the Sociedade Portuguesa de Doenças Metabólicas, Fátima, 8 a 10 de setembro de 2021
Resumo: Familial chylomicronaemia syndrome is caused by mutations in genes involved in the lipolytic cascade causing an abnormal persistence of chylomicrons (CM) during fasting. The resulting hypertriglyceridemia may lead to recurrent acute pancreatitis, eruptive xanthomata, lipemia retinalis, and hepatosplenomegaly. Mutations in the lipoprotein lipase (LPL) gene account for more than 80% of the cases of FCS reported in literature; other causes include the deficit of APOA5, GPIHBP1, APOC2 and LMF1. A three-month-old girl, second child of Pakistani consanguineous parents, with irrelevant personal and familial history, presented to the emergency department with a 1-week history of isolated episodes of vomiting. Clinically she had mild hepatosplenomegaly, no abdominal tenderness and no xanthomata. The initial blood draw had a milky appearance, with high levels of total cholesterol - TC (669 mg/dL), low-density lipoprotein cholesterol – LDL (181 mg/dL), and triglycerides – TG (6744 mg/dL); and low high-density lipoprotein cholesterol - HDL (6 mg/dL). The levels of apolipoprotein A1, apolipoprotein B, amylase and lipase were in the reference range. Ophthalmology evaluation was normal and abdominal ultrasound described liver, spleen and kidney in their normal superior size for age. Breastfeeding was replaced by a low-fat formula with subsequent decrease in 48 hours of TC (245 mg/dL) and TG (692 mg/dL) and normalization of HDL and LDL cholesterol. Complementary feeding was started at 6 months of age, with restriction of dietary fat of the total energy intake. We perform the genetic test by target sequencing where the genes associated with FCS were included. We found a homozygous deletion of exon 4 of the GPHIBP1 gene, under confirmation by long PCR. No point pathogenic variants or small deletions were found in these genes. Presently, at 12 months of age, she has adequate growth and psychomotor development, with normal plasmatic levels of CT, LDL and HDL and TG sustainably under 2000 mg/dl, without hepatosplenomegaly or pancreatitis. We believe exon homozygous 4 deletion in GPIHBP1 is the probable genetic cause in this case, as previously reported in a consanguineous Pakistani family by Berge et al, 2014.