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[Persistent hyperinsulinemic hypoglycemia in the newborn and infants]
P de Lonlay-Debeney1, J C Fournet, D Martin
1Département de pédiatrie, hôpital Necker-Enfants-Malades, Paris, France.
Insights
Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) presents heterogeneously. Distinguishing focal from diffuse lesions is crucial for appropriate surgical and genetic management, impacting treatment outcomes and risks.
Area of Science:
- Pediatric Endocrinology
- Medical Genetics
Background:
- Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the leading cause of hypoglycemia in infants.
- Clinical and histopathological presentations of PHHI are diverse, including focal and diffuse pancreatic lesions.
- Accurate diagnosis is critical due to differing therapeutic and genetic implications.
Purpose of the Study:
- To highlight the importance of differentiating between focal and diffuse forms of PHHI.
- To underscore the distinct management strategies and outcomes associated with each form.
- To review the genetic underpinnings of various PHHI subtypes.
Main Methods:
- Review of clinical presentations, histopathological findings, and treatment responses in PHHI cases.
- Analysis of genetic mutations associated with recessively and dominantly inherited PHHI.
- Comparison of surgical outcomes for focal versus diffuse pancreatic lesions.
Main Results:
- Focal PHHI lesions, characterized by localized islet cell hyperplasia, are curable with limited pancreatic resection.
- Diffuse PHHI lesions, involving the entire pancreas, necessitate subtotal pancreatectomy, increasing the risk of diabetes mellitus.
- Genetic causes include mutations in SUR1 and Kir6.2 genes for recessive forms, and glucokinase or glutamate dehydrogenase genes for dominant forms.
Conclusions:
- Distinguishing focal and diffuse PHHI is essential for guiding surgical intervention and genetic counseling.
- Focal PHHI offers a favorable prognosis with targeted resection, while diffuse PHHI presents significant long-term challenges.
- Understanding the genetic basis of PHHI is key to personalized treatment and family planning.
Abstract:
Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.