This case, presenting with bilateral impalpable testes, illustrates the relevance of a broad differential
disorders of sex development case management. It provides new insights on hypothalamic-pituitary-gonadal (HPG) axis and testicular function abnormalities in the multisystem disorder of
Lowe syndrome.
Lowe syndrome, also known as
oculocerebrorenal syndrome, is a rare disorder characterised by
eye abnormalities, central nervous system involvement and
proximal renal tubular acidosis. There are a handful of reports of pubertal delay,
infertility and
cryptorchidism in
Lowe syndrome. Biochemistry aged 72 h:
testosterone 6.4 nmol/L, LH <0.5 IU/L and FSH <0.5 IU/L.
Gonadotropin-releasing hormone stimulation test identified significantly raised baseline LH = 45.4 IU/L (contrasts with earlier undetectable LH), with a 20% increase on stimulation, while baseline FSH = 4.3 IU/L with no increase on stimulation. Day 14 HCG stimulation test produced an acceptable 50% increase in
testosterone. The constellation of further abnormalities suggested
Lowe syndrome:
hypotonia, bilateral
cataracts (surgical extraction and
intraocular lens implantation) and
renal tubular acidosis (microscopic haematuria,
hypercalciuria,
proteinuria, generalised aminoaciduria, hypophosphataemia and
metabolic acidosis).
DNA sequencing identified de novo hemizygous frameshift mutation OCRL c.2409_2410delCT in exon 22. Interpretation of initial and repeat
GnRH and HCG testing indicates the likelihood of testicular failure. Partial testicular descent occurred but left
orchidopexy was required. Improving long-term gonadal function in
Lowe syndrome assumes increased importance for current cohorts as advances in
renal replacement therapy have greatly improved life expectancy. Noting HPG axis abnormalities in
Lowe syndrome in infancy can identify cases requiring increased surveillance of pubertal progress for earlier detection and management.
LEARNING POINTS: Clinical endocrine problems in
Lowe syndrome has been reported, but has focused on abnormalities in adolescence and young adulthood: pubertal delay and
infertility.We present an infant with isolated LH elevation at baseline and on
GnRH stimulation testing who also had bilateral impalpable testes.Early testing of the HPG axis in patients with
Lowe syndrome may help predict gonadal abnormalities from a younger age, which will enhance the overall case management into adolescence.