Diabetes mellitus and insulin resistance associated with Kabuki syndrome—A case report and literature review

Thewjitcharoen, Yotsapon; Wanothayaroj, Ekgaluck; Nakasatien, Soontaree; Krittiyawong, Sirinate; Khurana, Ishant; El‐Osta, Assam; Himathongkam, Thep

doi:10.1002/ccr3.5736

Cited by 4 publications

(5 citation statements)

References 17 publications

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“…While other medications (eg, glucocorticoids, atypical antipsychotics, calcineurin inhibitors, and thiazide diuretics) could promote hyperglycemia ( 14 ), this patient was importantly not taking other predisposing medications. Additionally, although case reports describe an association of diabetes with Kabuki syndrome in adulthood ( 15 ), to our knowledge, no prior literature describes this association in children or the association of Kabuki syndrome and HHS in children or adults. Lastly, her history of chronic hypernatremia, which may be multifactorial in the context of chronic renal disease as well as potential chronic volume contraction, may have exacerbated her clinical presentation.…”

Section: Discussionmentioning

confidence: 97%

Diazoxide-related Hyperglycemic Hyperosmolar State in a Child With Kabuki Syndrome

Kahlon,

Stanley,

Lineen

et al. 2024

JCEM Case Reports

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Diazoxide is a commonly used first-line medication for the treatment of hyperinsulinism. Hyperglycemia may occur with diazoxide use. However, hyperglycemic hyperosmolar state (HHS) secondary to diazoxide is an exceedingly rare but potentially life-threatening adverse effect. We present a case of a 2-year-old with Kabuki syndrome and hyperinsulinism on diazoxide. She presented with 4 days of fever, respiratory symptoms, and lethargy. She was influenza B positive. Initial workup indicated HHS, with an elevated serum glucose (47.1 mmol/L [847.8 mg/dL]; reference range 3.9-6.0 mmol/L; 70-108 mg/dL), serum osmolality (357 mmol/kg H2O; reference 282-300 mmol/kg H2O) but absent urine ketones and no metabolic acidosis (venous pH 7.34). Her course was complicated by an acute kidney injury. Management in the hospital included discontinuation of diazoxide and intravenous fluid resuscitation, following which hyperglycemia and hyperosmolarity resolved. No insulin therapy was required. She remained normoglycemic without diazoxide for 2 weeks but subsequently required restarting of diazoxide for hypoglycemia. This case highlights the need for early recognition and prompt management of diazoxide-related HHS to reduce negative outcomes. We present the first case report of a child with Kabuki syndrome and hyperinsulinism with diazoxide-induced HHS.

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Section: Discussionmentioning

confidence: 97%

Diazoxide-related Hyperglycemic Hyperosmolar State in a Child With Kabuki Syndrome

Kahlon,

Stanley,

Lineen

et al. 2024

JCEM Case Reports

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“…Early molecular diagnoses help patients receive timely, targeted multidisciplinary care. They also allow families to understand the risks when choosing to expand their family and have access to appropriate reproductive options ( 2 , 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…The occurrence of T1DM in the absence of KS is usually sporadic in 90% of cases but may occurin patients with a family history of T1DM and HLA risk genotypes DR3/4-DQ8 or DR4/DR4 ( 6 ). Insulin-dependent diabetes secondary to pancreatic hypoplasia was diagnosed in another Japanese patient with the KMT2D mutation ( 4 ). In contrast, hyperinsulinaemic hypoglycaemia has been reported in cases of KS with KDM6A mutations ( 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…In a case series of 21 Chinese patients in Hong Kong with KS, the risk of T2DM was reported to be 20% (4/21) in early adulthood; all patients with T2DM had the KMT2D gene and 28.6% (6/21) of these patients were obese ( 8 ). In addition, a case report described a possible association between low birth weight and an increased risk of T2DM in KMT2D KS patients, hypothesised to be because of reduced pancreatic beta cell mass and insulin resistance from obesity in late childhood ( 4 ).…”

Section: Discussionmentioning

confidence: 99%

“…While neonatal hypoglycaemia from congenital hyperinsulinism is an established feature of KS, DM is an infrequently reported endocrine complication ( 4 ). It has been reported in obese patients and those with autoimmune DM ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

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Diabetes mellitus in Kabuki syndrome 1 on a background of post-transplant diabetes mellitus

Chew Sue Mei,

Pritchard,

Grayton

et al. 2024

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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Summary Kabuki syndrome is a genetic disorder characterised by distinctive facial features, developmental delays, and multisystem congenital anomalies. Endocrine complications such as premature thelarche and short stature are common, whereas disorders of glycaemic control are less frequent. We describe a 23-year-old white female referred to the diabetes clinic for hyperglycaemia during haemodialysis. She was subsequently diagnosed with Kabuki syndrome based on characteristic clinical features, confirmed by detecting a heterozygous pathogenic variant in KMT2D. She was known to have had multiple congenital anomalies at birth, including complex congenital heart disease and a single dysplastic ectopic kidney, and received a cadaveric transplanted kidney at the age of 13. She had hyperglycaemia consistent with post-transplant diabetes mellitus (DM) and was started on insulin. Examination at the time revealed truncal obesity. She developed acute graft rejection and graft failure 14 months post-transplant and she was started on haemodialysis. Her blood glucose levels normalised post-graft explant, but she was hyperglycaemic again during haemodialysis at the age of 23. Given her clinical phenotype, negative diabetes antibodies and normal pancreas on ultrasound, she was assumed to have type 2 DM and achieved good glycaemic control with gliclazide. Learning points Involve clinical genetics early in the investigative pathway of sick neonates born with multiple congenital anomalies to establish a diagnosis to direct medical care. Consider the possibility of Kabuki syndrome (KS) in the differential diagnoses in any neonate with normal karyotyping or microarray analysis and with multiple congenital anomalies (especially cardiac, renal, or skeletal), dysmorphic facial features, transient neonatal hypoglycaemia and failure to thrive. Consider the possibility of diabetes as an endocrine complication in KS patients who are obese or who have autoimmune disorders.

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