"Congruency the ART of Being Real" - 46XY DSD Due to 5 α Reductase Deficiency - Challenges in Decision Making.

Disorders of sexual development (DSDs) are heterogenous group of disorders characterized by discrepancy in chromosomal, gonadal, and phenotypic sex. DSD is a Medico-Social Emergency. 5 α reductase type 2 deficiency is one of the rare causes of 46 XY DSD. The degree of under virilization varies from clinically female to a near male phenotype. Müllerian structures were absent. At puberty, there might be features of virilization. Gender incongruence or dysphoria occurs frequently during puberty. An important marker for diagnosis is an elevated testosterone to dihydrotestosterone ratio in the basal state or following HCG stimulation. All 46 XY DSD require an appropriate molecular diagnosis prior to gender assignment and gender reassignment surgery. Gender reassignment surgery and/or Gonadectomy should be performed only after 18 years if there are compelling indications like suspicion of malignancy or presence of gender dysphoria or gender incongruence.

The Spectrum of CYP21A2 Gene Mutations from 16 Families of Congenital Adrenal Hyperplasia: Genotype-Phenotype Correlation.

Aim: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder of the adrenal steroidogenic pathway. The most common form of CAH is due to 21-hydroxylase deficiency resulting from mutations in CYP21A2 gene. The present study aimed to identify CYP21A2 common gene mutations, phenotype correlation, and to analyze the segregation pattern in CAH patients, parents, and siblings. Materials and Methods: Sixteen families having at least one classic CAH child in each family, a total of 58 subjects were recruited. The presence of six most common gene mutations, namely, Intron 2 (c.293-13A/C>G), c.844G>T (p.Val282Leu), c.1019G>A (p.Arg340His), c.92C>T (p.Pro31Leu), c.955C>T (p.Gln319*), and c.518T>A (p.Ile173Asn) in CYP21A2 gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using specific primers. Results: Out of 16 classic CAH females analyzed, salt-wasting (SW) form was present in 12 (75%) and simple virilizing form in four (25%) children. Isolated clitoromegaly was the most common clinical presentation followed by ambiguous genitalia. The most common mutation observed in CAH patient population was Intron 2 (c.293-13A/C>G) (100%) followed by p.Pro31Leu (98%), p.Gln319* (93%), p.Val282Leu (91.4%), and p.Ile173Asn (19%). Although p.Arg340His mutation was not observed in this study. Interestingly, Intron 2 (c.293-13A/C>G) homozygous was observed in 31.3% of the entire study cohort and p.Ile173Asn mutation was found to be associated with SW form. Conclusions: Our results suggested a high prevalence of CYP21A2 gene mutations among CAH patients and heterogeneous mutation spectrum in their families of south Indian cohort. The outcomes afford valuable evidence for premarital and prenatal screening as well as planning suitable programs to prevent the development of CAH in Indian population.

HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA: A NOVEL HOMOZYGOUS MUTATION IN SLC34A3 AND LITERATURE REVIEW.

OBJECTIVE: Hypophosphatemic rickets with hypercalciuria (HHRH) is a rare, recessively-inherited form of rickets caused by homozygous or compound heterozygous mutations in the SLC34A3 gene that encodes the renal tubular phosphate transporter protein NaPi2c. The bone phenotype varies from severe rickets to no disease. Accurate diagnosis is important as the treatment differs from other forms of rickets. METHODS: The patient was a 12-year-old boy from the Indian subcontinent with florid hypophosphatemic rickets. A targeted gene panel to search for mutations in genes associated with inherited forms of rickets was performed. We also completed a literature search of published cases of HHRH. RESULTS: The targeted gene panel demonstrated a novel homozygous SLC34A3 mutation: c.1339 G>A (p.Ala447Thr). His parents were heterozygous for the mutation. In our literature review we found that people with homozygous SLC34A3 mutations were more likely to have rickets than those with compound heterozygous mutations (85% versus 45%, p<0.002) and that serum phosphate z scores were lower in those with rickets than those without (-3.3 with a standard deviation of 1.5 versus -2.1 with a standard deviation of 1.5, p<0.005). CONCLUSION: The bone phenotype of HHRH is related to the nature of the mutation and serum phosphate levels. Targeted gene panels can aid in the accurate diagnosis of inherited forms of rickets, and facilitate correct treatment.