Cholestasis and Hepatic Iron Deposition in An Infant With Complex Glycerol Kinase Deficiency
Cholestasis and Hepatic Iron Deposition in An Infant With Complex Glycerol Kinase Deficiency
Cholestasis and Hepatic Iron Deposition in An Infant With Complex Glycerol Kinase Deficiency
TABLE 2 Results of the Comparative Genomic Hybridization Microarray Study for Our Patient
Chromosomal Region Minimum Size of Maximum Size of Maximum Boundaries (Base Pair Potential Disease(s) or Gene(s) That May Be
Affected Lossa Lossa Coordinates) Associated With This Region
Xp21.3p21.1 ∼7683.0 kb ∼77347.7 kb chrX:25800484–33535137 DMD, GK, IL1RAPL1, NR0B1
Chromosome Xp21 deletion syndrome
Online Mendelian Inheritance in Man: 300679
a A minimum size value represents the actual base pair coordinates of the probes detected as a copy number change, whereas a maximum size value includes the gap distances to
bordering unaffected probes that may potentially include additional materials involved in the change detected.
kinase levels were confirmed to be indirectly by measuring serum the first week of life was likely his
elevated at 4384 μmol/L (normal glycerol levels.3,7 When patients first manifestation of his AHC. When
13–66 μmol/L). are also missing either of both an infant presents with symptoms
the dystrophin gene and/or the of adrenal insufficiency, clinicians
Ultimately, a comparative genomic
Nuclear Receptor Subfamily 0, must rightly consider congenital
hybridization microarray study was
Group B, Member 1 (NR0B1) gene, adrenal hyperplasia, as it has a
done, which confirmed an Xp21
the condition is known as complex much higher incidence of 1:5000 to
deletion (Table 2). His mother was
GKD or Chromosome Xp21 deletion 1:15 000 compared with 1:140 000 to
also found to be a carrier of this
syndrome due to the contiguous 1:1 200 000 for AHC.8,9 Importantly,
deletion by fluorescence in situ
position of all 3 loci on the short AHC usually presents with normal
hybridization study.
arm of the X chromosome.2 Each 17-hydroxyprogesterone levels,
Our patient was started on gene deletion contributes to the excluding the most common cause of
replacement fludrocortisone phenotype, with the deletion of the congenital adrenal hyperplasia.10–12
and hydrocortisone; within 4 dystrophin gene causing weakness In addition, given AHC’s involvement
days, his plasma renin activity and muscle breakdown consistent of the entire adrenal gland, it has
levels normalized. Over the with DMD, the deletion of the NR0B1 the potential for an Addisonian-like
course of the next few weeks, his gene causing AHC due to a deficiency presentation of hyperpigmentation,
hyperpigmentation, feeding skills, of the DAX-1 protein and finally, which can help differentiate it from
and weight gain also improved and the deletion of the glycerol kinase other forms of adrenal insufficiency.
he was discharged from the hospital. gene causing elevated glycerol Our patient was born with light
levels.8 When all 3 genes are deleted, brown skin (Fig 1), which darkened
the presentation of this recessive significantly in the first week of life
DISCUSSION X-linked condition is more severe and (Fig 2).
occurs in the infantile period. Due to
GKD can exist alone as an isolated We believe our patient’s persistent
the involvement of NR0B1 in gonadal
deficiency and may cause a Reye-like direct hyperbilirubinemia with
development, cryptorchidism may be
syndrome of vomiting, metabolic biopsy-confirmed cholestasis was
present, as in our patient, and there is
acidosis, and ketotic hypoglycemia also likely related to his AHC. The
potential for later hypogonadotropic
due to hyperglycerolemia and relationship between cortisol
hypogonadism during puberty.8
glyceroluria.2 However, it is often deficiency and cholestasis has been
asymptomatic and discovered Most patients with complex GKD well-described.13 Although the
incidentally later in life through involving the AHC loci will present mechanism is not well understood,
hyperlipidemia testing, given many with an acute adrenal crisis in the it may be related to cortisol’s effect
laboratories’ standard methodology first few weeks to months of life. Our on bile formation. In 1 case series
of reporting serum triglycerides patient’s presumed septic crisis in of 4 neonates with severe cortisol
ABBREVIATIONS
AHC: adrenal hypoplasia
congenita
CK: creatine kinase
DMD: Duchenne muscular
dystrophy
FIGURE 2 GKD: glycerol kinase deficiency
Our patient’s pigmentation at the time of NR0B1: Nuclear Receptor
presentation to our institution at 6 weeks of
FIGURE 1 Subfamily 0, Group B,
age.
Our patient’s skin pigmentation immediately Member 1
after birth.
There have, however, been several
deficiency, cholestasis resolved case reports of patients with
with hydrocortisone replacement.13 adrenal insufficiency who were
found to have increased hepatic REFERENCES
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CONCLUSIONS
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