Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease – A Rare Case Concerning <i>PMM2</i> Gene Pleiotropy

Soares, Ana Rita; Figueiredo, Carla; Quelhas, Dulce; Silva, Ermelinda Santos; Freitas, Joana; Oliveira, Maria João; Faria, Maria do Sameiro; Fortuna, Ana María; Borges, Teresa

doi:10.17925/ee.2020.16.1.66

Cited by 7 publications

(6 citation statements)

References 7 publications

(6 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All of these patients also carried a compound heterozygote for a second missense mutation in PMM2 (p.Arg141His, p.Asp148Asn or p.Phe157Ser), pathogenic for CDG type 1a, with an AR inheritance pattern [ 11 ]. Soares et al also described a 6-year-old female with similar association [ 17 ]. Our patients were heterozygous in the PMM2 gene for a sequence variant c.368G > A, which has been reported to be causative for CDG-Ia [ 18 ] They were also heterozygous in the PMM2 gene for a pre-coding sequence variant c.167G > T, known to cause disease in 17 patients from 11 European families who presented with HH and PKD [ 3 ].…”

Section: Discussionmentioning

confidence: 89%

Hyperinsulinemic Hypoglycemia Due to PMM2 Mutation in Two Siblings with Autosomal Recessive Polycystic Kidney Disease

Acharya

Upadhyay

2022

Pediatric Reports

View full text Add to dashboard Cite

Background: Hyperinsulinemic hypoglycemia (HH) is an important cause of persistent hypoglycemia in newborns and infants. Recently, PMM2 (phosphomannomutase 2) mutation has been associated with HH, especially in conjunction with polycystic kidney disease (PKD). PMM2 deficiency is one of the most common causes of congenital disorder of glycosylation (CDG). Renal involvement in PMM2-CDG manifests as cystic kidney disease, echogenic kidneys, nephrotic syndrome or mild proteinuria. Case Summary: Here, we describe a pair of siblings with HH associated with autosomal recessive polycystic kidney disease (ARPKD) and PMM2 mutation. Two siblings with ARPKD presented during infancy and early toddler years with severe hypoglycemia. Both had inappropriately elevated serum insulin, low β-hydroxybutyrate, a need for a high glucose infusion rate, positive glycemic response to glucagon, positive diazoxide response and PMM2 mutation. Conclusions: Although this combination of HH and PKD was recently described in patients of European descent who also had PMM2 mutation, our report is unique given that these non-consanguineous siblings were not exclusively of European descent. PMM2 mutation leading to abnormal glycosylation and causing cystic kidneys and the alteration of insulin secretion is the most likely pathogenesis of this clinical spectrum.

show abstract

Section: Discussionmentioning

confidence: 89%

Hyperinsulinemic Hypoglycemia Due to PMM2 Mutation in Two Siblings with Autosomal Recessive Polycystic Kidney Disease

Acharya

Upadhyay

2022

Pediatric Reports

View full text Add to dashboard Cite

show abstract

“…Soares et al. presented another case of CHI and polycystic kidneys with that particular PMM2 variant ( 106 ). Chen et al.…”

Section: Resultsmentioning

confidence: 99%

Syndromic forms of congenital hyperinsulinism

2023

View full text Add to dashboard Cite

Congenital hyperinsulinism (CHI), also called hyperinsulinemic hypoglycemia (HH), is a very heterogeneous condition and represents the most common cause of severe and persistent hypoglycemia in infancy and childhood. The majority of cases in which a genetic cause can be identified have monogenic defects affecting pancreatic β-cells and their glucose-sensing system that regulates insulin secretion. However, CHI/HH has also been observed in a variety of syndromic disorders. The major categories of syndromes that have been found to be associated with CHI include overgrowth syndromes (e.g. Beckwith-Wiedemann and Sotos syndromes), chromosomal and monogenic developmental syndromes with postnatal growth failure (e.g. Turner, Kabuki, and Costello syndromes), congenital disorders of glycosylation, and syndromic channelopathies (e.g. Timothy syndrome). This article reviews syndromic conditions that have been asserted by the literature to be associated with CHI. We assess the evidence of the association, as well as the prevalence of CHI, its possible pathophysiology and its natural course in the respective conditions. In many of the CHI-associated syndromic conditions, the mechanism of dysregulation of glucose-sensing and insulin secretion is not completely understood and not directly related to known CHI genes. Moreover, in most of those syndromes the association seems to be inconsistent and the metabolic disturbance is transient. However, since neonatal hypoglycemia is an early sign of possible compromise in the newborn, which requires immediate diagnostic efforts and intervention, this symptom may be the first to bring a patient to medical attention. As a consequence, HH in a newborn or infant with associated congenital anomalies or additional medical issues remains a differential diagnostic challenge and may require a broad genetic workup.

show abstract

“…The former may be possible since HIPKD is a newly reported disease and more individuals with HIPKD may be diagnosed as the disease becomes more recognised in the scientific and medical community. Indeed, subsequent families have been described and it is possible that some patients previously considered to have ARPKD but without genetic confirmation may now have their diagnosis corrected to HIPKD (Moreno Macián F et al, 2020;Soares et al, 2020). In fact, the phenotypic range associated with these promoter mutations may extend beyond HIPKD (Dorval et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD)

Islam

Tekman

Flanagan

et al. 2021

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background: Polycystic kidney disease with hyperinsulinaemic hypoglycaemia (HIPKD) is a recently described disease caused by a single nucleotide variant, c.-167G>T, in the promoter region of PMM2 (encoding phosphomannomutase 2), either in homozygosity or compound heterozygosity with a pathogenic coding variant in trans. All patients identified so far are of European descent, suggesting a possible founder effect. Methods: We generated high density genotyping data from 11 patients from seven unrelated families, and used this information to identify a common haplotype that included the promoter variant. We estimated the age of the promoter mutation with DMLE+ software, using demographic parameters corresponding to the European population. Results: All patients shared a 0.312 Mb haplotype which was absent in 503 European controls available in the 1000 Genomes Project. The age of this mutation was estimated as 105-110 generations, indicating its occurrence around 600 BC, a time of intense migration, which might explain the presence of the same mutations in Europeans around the globe. Conclusion:The shared unique haplotype among seemingly unrelated patients is consistent with a founder effect in Europeans.

show abstract

Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease – A Rare Case Concerning PMM2 Gene Pleiotropy

Cited by 7 publications

References 7 publications

Hyperinsulinemic Hypoglycemia Due to PMM2 Mutation in Two Siblings with Autosomal Recessive Polycystic Kidney Disease

Hyperinsulinemic Hypoglycemia Due to PMM2 Mutation in Two Siblings with Autosomal Recessive Polycystic Kidney Disease

Syndromic forms of congenital hyperinsulinism

Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD)

Contact Info

Product

Resources

About