<scp><i>PHKA2</i></scp> variants expand the phenotype of phosphorylase B kinase deficiency to include patients with ketotic hypoglycemia only

Benner, Anne; Alhaidan, Yazeid; Lines, Matthew A.; Brusgaard, Klaus; León, Diva D. De; Sparkes, Rebecca; Frederiksen, Anja Lisbeth; Christesen, Henrik Thybo

doi:10.1002/ajmg.a.62383

Cited by 3 publications

(4 citation statements)

References 29 publications

(60 reference statements)

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“…Boys are more likely to carry mutations in the PHKA2 gene, which is known to be connected with IKH [11]. Furthermore, it was claimed that IKH is common in African children with chronic malnutrition or severe malaria [12,13].…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

“…Genetic analysis: Mutations in PHKA2 have been detected in a number of children with IKH [11]. Moreover , trio exome sequencing has discovered mutations including SLC16A1 (MCT1), NCOR1, IGF2BP1, SGLT2 and NEK11 as potential novel causes in children with otherwise unexplained KH [5].…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

“…Data on the incidence and prevalence of IKH are sparse; however, IKH is the most common diagnosis assigned to episodes of hypoglycemia in children in emergency departments in the United States [ 9 ]. According to literature reviews, IKH has been observed to be more prevalent in boys [ 2 , 10 ], who are more likely to carry mutations in the PHKA2 gene known to be connected with IKH [ 11 ]. Furthermore, it was claimed that IKH is common in African children with chronic malnutrition or severe malaria [ 12 , 13 ].…”

Section: Epidemiologymentioning

confidence: 99%

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Idiopathic ketotic hypoglycemia in children: an update

Metwalley,

Farghaly

2024

Ann Pediatr Endocrinol Metab

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Idiopathic ketotic hypoglycemia (IKH ) is defined as bouts of hypoglycemia with increased blood or urine ketones that occur in certain children after prolonged fasting or during illness .IKH is divided into physiological IKH which most frequently observed in normal children with inter current acute illness and pathological IKH which are seen in children who lack counter-regulatory hormones or in children with some metabolic disease or Silver-Russell syndrome .The typical patient is a young child between the ages of 10 months and 6 years.Episodes nearly always occur in the morning after an overnight. Symptoms include those of neuroglycopenia, ketosis, or both. IKH may be diagnosed after the ruling out various metabolic and hormonal condition associated with KH . Providing sufficient amounts of carbohydrates and protein, avoidance of prolonged fasting, increased frequency of feedings are main lines of treatment of IKH . It is crucial to understand the pathogenesis of IKH and to distinguish physiological IKH from pathological IKH . In this mini-review, we present a brief review of IKH as regard definition, types , clinical presentation, , diagnosis and therapeutic approach of IKH in children.

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Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

Section: Epidemiologymentioning

confidence: 99%

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Idiopathic ketotic hypoglycemia in children: an update

Metwalley,

Farghaly

2024

Ann Pediatr Endocrinol Metab

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“…Ketotic hypoglycemia (KH) can be caused by a range of metabolic and hormonal diseases, including glycogen storage disease (GSD) type 0, III, VI and IX, and growth hormone or cortisol deficiency. 1,2 A larger part of KH patients have idiopathic KH, a diagnosis of exclusion believed to represent a genetic and clinical heterogeneous disease entity. 3,4 Idiopathic KH can be divided into physiological KH and pathological KH, the latter often being under-diagnosed and under-treated due to the widespread misconception that all idiopathic KH represents normal variation.…”

Section: Introductionmentioning

confidence: 99%

Ketotic hypoglycemia in patients with Down syndrome

Drachmann

Carrigg²,

Weinstein

et al. 2021

JIMD Reports

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Background: Ketotic hypoglycemia (KH) without an identifiable underlying metabolic or hormonal disease is historically named idiopathic KH. The prevalence is unknown, but idiopathic KH is considered the most frequent cause of hypoglycemia beyond the neonatal period. KH in Down syndrome (DS) has not been reported. Methods:We conducted a web-based survey on KH in DS through the nonprofit patient organization Ketotic Hypoglycemia International. The responses were evaluated for consistency with KH by two authors. Two DS patient histories with documented KH were shared in more details. Results: Survey data on 139 DS patients were obtained. After validation, 10 patients (7.2%) had reported episodes of documented hypoglycemia, ketosis, and/or symptoms compatible with KH beyond the neonatal period. Glucose concentrations ranged 1.2-2.9 mmol/L; betahydroxybutyrate was up to 5.5 mmol/L during hypoglycemia. One girl had trisomy 21 with no response to i.m. glucagon also had a heterozygous Xp22.23 deletion including GYG2, which protein, glycogenin 2, is a substrate for glycogen synthase. Treatment with extended release cornstarch was effective.Conclusion: This is the first demonstration of a possible high prevalence of KH in DS. Even though this finding needs to be confirmed in other research settings, identification of KH in DS could have a dramatic impact, as simple treatments with cornstarch, protein and frequent meals may prevent KH attacks and, analogous to other conditions with KH, improve growth, stamina and prevent overeating and obesity. GYG2 deletion may contribute to KH in DS, resembling glycogen storage disease type 0.

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Glycogen storage disorder types IX: the mutation spectrum and ethnic distribution

Geramizadeh,

Ezgu,

Beyzaei

2024

Orphanet J Rare Dis

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Glycogen storage disorders (GSD) GSD-IX are characterized by deficiencies in muscular and/or hepatic phosphorylase enzymes. GSD type IX za is an X-linked disorder, while IXb and IXc are autosomal recessive disorders resulting from pathogenic variants in the genes encoding the Phosphorylase b Kinase regulatory subunit alpha (PHKA), beta (PHKB), and gamma (PHKG), respectively. Despite progress in understanding these diseases, there are still unclear questions regarding their clinical manifestations, genetic variations, and the relationship between genotype and phenotype. Therefore, this review focuses on variants of GSD IX subtypes and all clinical findings to establish a genotype–phenotype relationship as well as highlighting the wide spectrum of disease-causing variants. Such information is beneficial for the establishment of a privileged mutation screening process in a specific region or ethnic group. Diagnosis is based on clinical manifestations and laboratory test results, but molecular analysis is often necessary to distinguish the various forms with similar presentations.

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PHKA2 variants expand the phenotype of phosphorylase B kinase deficiency to include patients with ketotic hypoglycemia only

Cited by 3 publications

References 29 publications

Idiopathic ketotic hypoglycemia in children: an update

Idiopathic ketotic hypoglycemia in children: an update

Ketotic hypoglycemia in patients with Down syndrome

Glycogen storage disorder types IX: the mutation spectrum and ethnic distribution

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