Complex Glycerol Kinase Deficiency and Adrenocortical Insufficiency in Two Neonates

Abstract

Contiguous gene deletions of chromosome Xp21 can lead to glycerol kinase deficiency and severe adrenocortical insufficiency (AI) in a male newborn among other problems. We describe our experience with two such patients who presented with dysmorphic facies, AI, and pseudo-hypertriglyceridemia. Both infants had normal serum 17-hidroxyprogesterone levels, and adrenal glands could not be observed with ultrasonography. Creatine kinase and triglyceride levels were measured to elucidate the etiology of adrenal hypoplasia and were above normal limits in both cases. Both patients required steroid and salt supplementation. They were both found to have Xp21.2 deletions (DMD, NR0B1, GK, IL1RAPL1). We conclude that AI in the context of other genetic abnormalities should prompt chromosomal investigations in the absence of another unifying explanation.

Diagnosis of Hypoaldosteronism in Infancy

“…CGKD develops from partial deletion of the Xp21 chromosomal locus involving all or part of the gene for glycerol kinase deficiency (GKD) together with that for AHC and/or Duchenne muscular dystrophy (DMD). Much larger deletions including the ornithine transcarbamylase locus have also been described [86][87][88]. The syndrome can be both sporadic and familial, and the phenotype varies according to the extension of deleted DNA [89].…”

“…The syndrome can be both sporadic and familial, and the phenotype varies according to the extension of deleted DNA [89]. Patients with CGKD may show dysmorphic features including prominent eyebrows and forehead and depressed nasal root giving the face an hourglass appearance [86]. Mental impairment is also described, but specific causes have not been clearly defined.…”

IL1RAPL1 Gene Deletion in a Female Patient with Developmental Delay and Continuous Spike-Wave during Sleep

“…7 In some cases, IL1RAPL1 is deleted as a part of larger chromosomal deletion that often involves neighboring genes on the X-chromosome including dystrophin (DMD), glycerol kinase (GK), and DAX-1 (also known as NR0B1 , nuclear receptor subfamily 0, group B, member 1). 8 9 10 11 12 Thus, the features associated with deletions that include part or all of IL1RAPL1 may present with clinical signs of muscular dystrophy, glycerol kinase deficiency, and/or adrenal hypoplasia congenita. Hence, the clinical spectrum associated with pathogenic deletions that include IL1RAPL1 is diverse.…”

Deficiencia de glicerolcinasa: una causa metabólica de retraso global del desarrollo

“…Puede clasificarse como GKD aislada o compleja. En la forma aislada, solo se afecta el gen GK, mientras que la forma infantil compleja resulta de un síndrome de deleción del gen contiguo Xp21 de tamaño variable, que incluye el locus GK de hipoplasia suprarrenal congénita, los loci de distrofia muscular de Duchenne, o ambos [4,5]. Las características clínicas de un paciente con GKD compleja dependen de los loci involucrados y generalmente se asocian con una mayor morbilidad y mortalidad que la forma aislada [1].…”

“…El diagnóstico de GKD debe sospecharse ante una hipertrigliceridemia inexplicable [6]. Esta 'pseudohipertrigliceridemia' representa un artefacto en la prueba de triglicéridos, que se basa en la medición de glicerol libre, el componente acumulado en la GKD [4,10]. La determinación de los niveles de glicerol en la orina (gliceroluria) es un método simple para identificar la GKD y se puede detectar con mediciones de ácido orgánico en la orina mediante cromatografía de gases-espectrometría de masas [15].…”