K S H de Silva

Growth hormone releasing hormone receptor codon 72 mutation in a cohort of Sri Lankan patients with growth hormone deficiency.

INTRODUCTION Growth hormone releasing hormone receptor (GHRH-R) codon 72 mutation is recognised as a common genetic cause of growth hormone deficiency (GHD) in the Indian subcontinent resulting in a characteristic lean phenotype. Genetic studies have not been previously carried out in Sri Lankans with GHD. METHODS Patients with GHD presenting to a tertiary care referral centre were studied for GHRH-R codon 72 mutation by PCR amplification and sequencing. The phenotype of the cohort was described as the BMI SDS (Body mass index standard deviation score) based on the anthropometric data at the time of diagnosis. RESULTS Among 91 patients from 88 families studied, eight (6 boys) carried the codon 72 mutation. The presence of this mutation was low among the Sinhalese ethnicity (3 out of 68) than among Tamil and Moor ethnicities. BMI SDS of <-2 was seen in 71% of mutation positive and 45.8% of mutation negative patients. CONCLUSIONS Prevalence of GHRH-R codon 72 mutation in this group of GH deficient patients was 8.8%. The lean phenotype observed in 71% of the mutation positive patients was not a significant association when compared to a similar phenotype in 45.8% of the mutation negative patients.

Androgen insensitivity syndrome in a cohort of Sri Lankan children with 46, XY disorders of sex development (46, XY DSD).

INTRODUCTION There are several conditions giving rise to 46, XY disorders of sex development (DSD) with different modes of inheritance. Therefore definitive diagnosis based on molecular genetic confirmation would be the ideal to counsel parents regarding the future implications of the condition affecting their baby. This is the first report from Sri Lanka documenting the presence of mutations in the androgen receptor (AR) gene in a cohort of children with 46, XY DSD. OBJECTIVES To describe the socio-demographic and clinical features and document the presence of mutations in the androgen receptor (AR) gene in a cohort of children with 46, XY DSD. METHODS 46, XY patients with ambiguous genitalia followed up in the University Unit at the Lady Ridgeway Hospital, Colombo, and clinically identified as having androgen insensitivity syndrome (AIS) or a testosterone biosynthetic defect were recruited for the study. Their socio-demographic details and clinical features were documented. Exons 1 to 8 of the AR gene were screened for mutations by DNA sequencing on a venous blood sample. SRY gene mutations were also assayed. RESULTS Thirty-four patients were studied, 3 of whom were clinically diagnosed as having complete androgen insensitivity syndrome (CAIS). Sex of rearing was female and male in 4 and 30 respectively. AR gene mutations were detected in 6 patients (17.6%). None of the patients had SRY gene mutations. CONCLUSIONS Majority (88%) of the patients were raised as males. Six patients (17.6%) including the 3 with CAIS, had genetically confirmed AIS with the detection of AR gene mutations.

Multiple subcutaneous folds in oculocerebrorenal syndrome of Lowe

A 3-months old infant born to non-consanguineous parents was evaluated for hypotonia and developmental delay. He had a cataract in left eye, congenital glaucoma and megalocornea in right eye with no other dysmorphism. Anterior fontanelle was widely open. He was hypotonic with diminished tendon reflexes. Hypermobility was noted around both elbows and knees. There were unusual multiple skin folds with generalised increase in subcutaneous tissue noted in the limbs (Figure 1). His weight was between mean and -1SD.

Auxological outcome of growth hormone therapy at cessation of treatment in a cohort of growth hormone deficient Sri Lankan patients

INTRODUCTION Recombinant human growth hormone (r-hGH) for growth hormone deficiency (GHD) has been available free in the state hospitals of Sri Lanka since 2009. OBJECTIVES The aims were to compare height standard deviation scores (SDS) before and after treatment and compare heights at final assessment in relation to the target height (TH) and TH range. METHODS Patients with confirmed GHD followed up at the University Unit of the Lady Ridgeway Hospital, Colombo were studied. Anthropometric data were prospectively recorded from presentation to cessation of therapy. The height SDS before and after treatment were calculated and the heights at final assessment were compared with the TH and TH range. RESULTS Sixteen patients (15 boys) had completed treatment. The mean age at diagnosis was 145.38 (SD=34.28) months with a mean skeletal age of 97.5 (SD=42.85) months. Mean ages at commencement was 164.75 (SD=36.81) months and at cessation of therapy 212.06 (SD=30.12) months duration of therapy was 47.31 (SD=23.99) months.Majority had isolated GHD and 8 patients had pituitary hypoplasia on neuro-imaging. The height SDS improved significantly with treatment from -4.438 (1.18) to -3.37 (0.81), p<0.001. When finally assessed at ages ranging from 15 years 10 months to 26 years 9 months, one patient had reached the TH while six were in the TH range. CONCLUSIONS Auxological response to therapy was significant although treatment was started late due to financial constraints.