Hypercalcemia in an Infant with Primary Hyperoxaluria Type 2: A Novel Association.

Hypercalcemia in infants presents with a variety of clinical features and the etiology of hypercalcemia varies with age. Here we present a case of hypercalcemia in an infant presenting with nephrocalcinosis and nephrolithiasis. Our investigations led us to a diagnosis of primary hyperoxaluria (PH) type 2, a rare metabolic disorder, along with hypercalcemia, a never before reported association. A 9-month-old female presented with urinary tract infection and systemic features requiring hospitalization and parenteral antibiotics. Investigations revealed bilateral medullary nephrocalcinosis. Genetic testing revealed a diagnosis of Primary hyperoxaluria type 2 with two possible mutations. Sanger sequencing of the parents identified the pathogenic mutation in the mother. This is the first report of a genetically proven case of primary hyperoxaluria type 2 associated with hypercalcemia.

A Rare Differences of Sex Development: Male Sex Reversal Syndrome (NonSyndromic 46, XX with Negative Sex-Determining Region of Y Chromosome Gene).

46, XX testicular differences of sex development (DSD) is a rare cause of DSD presenting as a phenotypical male with chromosomal sex of 46, XX. Sex-determining region of the Y chromosome (SRY)-positive 46, XX DSDs have a well-characterized pathogenetic mechanism, whereas in SRY-negative 46, XX DSDs, the pathogenesis is not clearly delineated. Herein, we present a case of a 3½-year-old child who presented with ambiguous genitalia and bilateral palpable gonads. On the basis of a karyotype and fluorescent in situ hybridization, we arrived at a diagnosis of SRY-negative 46, XX testicular DSD. Basal serum estradiol and human menopausal gonadotrophin stimulated estradiol levels and inhibin A blood levels were against the presence of any ovarian tissue. Imaging of the gonads showed bilateral normal-looking testis. A clinical exome sequencing revealed a heterozygous missense variant NR5A1:c275G>A (p. Arg92gln) located at exon 4 in the affected child. Protein structure analysis was further performed, and the variant was found to be highly conserved. Sanger's sequencing showed that the mother was heterozygous for the variant detected in the child. This case highlights the rarity of SRY-negative 46, XX testicular DSD with a unique variant. Largely under characterized, this group of DSDs needs to be reported and analyzed to add to the spectrum of presentation and genetic characteristics. Our case is expected to add to the database, knowledge, and approach to cases of 46, XX testicular DSD.

Aromatase deficiency in a tall man: Case report of two novel mutations and review of literature.

Aromatase (CYP19A1) is the only enzyme known to catalyse the conversion of androgen to estrogen. Aromatase deficiency occurs due to mutation in CYP19A1gene which has an autosomal recessive inheritance pattern. It leads to decrease in estrogen synthesis and delayed epiphyseal closure, eunuchoid habitus and osteopenia. We are presenting here, a 24 years old male, with history of progressive increase in height and knock knees. X-ray showed open wrist and knee epiphysis. The serum testosterone level was normal and serum estradiol level was undetectable. Semen analysis showed azoospermia. Clinical exome sequencing gave two novel mutations in CYP19A1. The first variant was a novel single nucleotide deletion of thiamine at 570th base of the cDNA (c.570delT) of CYP19A1 gene. The second variant detected was again a novel one in the same gene in Exon 5 corresponding 344th base of the cDNA (c344G>A) resulting in a missense mutation of 115th arginine to glutamine in the protein. Sanger sequencing showed that the later mutation was inherited from the father. The patient was started on oral estradiol valerate for epiphyseal closure to prevent further increase in height. Only 15 mutations have been reported in the aromatase gene in males till date, our report of these novel mutations will be an add-on to the literature.