Does GnRH analog improve the final height in Thai girls with idiopathic central precocious puberty?

Ten Thai girls with idiopathic central precocious puberty (ICPP) were treated with gonadotrophin releasing hormone (GnRH) analog for a mean period of 1.5+/-0.4 years. The predicted adult height at the end of treatment was significantly higher than that at the start of treatment (158.2+/-7.9 vs 153.0+/-8.7 cm, p=0.009). In addition, treatment with GnRH analog could significantly regress the breast staging from 3.4+/-0.8 to 2.6+/-1.0 (p=0.04),but not the pubic hair staging. Five of them reached a final height which was not significantly higher than the predicted adult height before treatment (153.1+/-4.8 vs 150.7+/-1.0 cm, p=0.5). In conclusion, treatment with GnRH analog in Thai girls with ICPP can improve the predicted adult height and regress the breast staging. However, the improvement of final height is not promising.

Clinical and molecular characteristics of Thai patients with achondroplasia.

Achondroplasia is an autosomal dominant disorder characterized by disproportionately short stature, frontal bossing, rhizomelia, and trident hands. Most patients appear sporadically resulting from a de novo mutation associated with advanced paternal age. A glycine to arginine mutation at codon 380 (G380R) of the fibroblast growth factor receptor 3 gene (FGFR3) was found to be the most common cause of achondroplasia in various populations. We identified and clinically characterized 3 Thai patients with achondroplasia. In all of them, we also successfully identified the G380R mutation supporting the observation that this is the most common mutation in achondroplasia across different ethnic groups including Thai.

A case of Pfeiffer syndrome type 1 with an A344P mutation in the FGFR2 gene.

Pfeiffer syndrome, an autosomal dominant disorder, consists of craniosynostosis, broadening of the thumbs and great toes, and partial soft tissue syndactyly of the hands and feet. Three clinical subtypes have been classified mainly for the purpose of genetic counseling. Mutations in FGFR1 and FGFR2 are known to be associated with the syndrome. However, the correlation between genotype and phenotype is not well defined. Only one patient with Pfeiffer syndrome with no other clinical information has been reported to have had an A344P mutation of the FGFR2. Here we report a Thai male patient with sporadic Pfeiffer syndrome type 1 with impaired intelligence (IQ = 77). Mutation analysis revealed A344P in FGFR2. Identification of the clinical features and molecular defects in more patients is required to better correlate the genotype and phenotype of this complex syndrome.

A cost-benefit of gnRH stimulation test in diagnosis of central precocious puberty (CPP).

The GnRH stimulation test is the gold standard to diagnose central precocious puberty (CPP). Conventionally, we need at least 2 hours to finish the test which seems to be costly and time consuming. In this study, we described the pattern of LH and FSH levels during the GnRH test in 27 girls who presented with various degrees of precocious puberty. We found that the blood samples at 90 and 120 min after GnRH were not necessary. To save the cost of diagnosis, the basal LH/FSH ratio > 0.2, the 30 min LH/FSH ratio after GnRH > 0.9 and the peak LH/FSH ratio > 1.0 can be used to diagnose CPP with positive predictive values (PPV) of 87.3, 89.4 and 93.8 per cent respectively.

Establishing gas chromatography-mass spectrometry to diagnose organic acidemias in Thailand.

Disorders of organic acid metabolism are a group of disorders which has long been ignored by majority of Thai physicians. Part of this is due to lack of laboratories in Thailand to verify the diagnosis of the disorders. We have recently developed a technique to qualitatively analyze organic acids utilizing Gas Chromatography-Mass Spectrometry (GC-MS). Eight patients in four families were successfully identified as having organic acidemias (OA) by this method. Two families had methylmalonic acidemia, one had propionic acidemia, and the other had 3-methylcrotonyl CoA carboxylase deficiency. To our knowledge, this is the first laboratory in Thailand being able to use GC-MS to diagnose OA. Availability of a laboratory in Thailand and affordability of the test are expected to result in earlier diagnosis and identification of more cases of OA in Southeast Asian countries. Consequently, prompt and proper treatment can be anticipated which should lead to better prognosis for patients with this group of disorder.

Neonatal screening for hypothyroidism at a university hospital in Thailand.

Neonatal screening is an essential program for early identification of congenital hypothyroidism. Between July 1991 and May 1998, 37, 262 infants born at Chulalongkorn Hospital were enrolled to the screening program. Blood TSH levels were determined on infants at > or = 48 hours after birth. They were performed in dried blood sample taken by heel prick on filter papers. TSH levels were measured by fluoroimmunoassay from July 1991 to December 1997 and by immunoradiometric assay from January to May 1998. Infants with TSH screening level higher than the cut off level (20 mu/l) were recalled for re-evaluation which consist of complete physical examination and blood test for serum T4 and TSH. Bone age determination and thyroid scan using technetium-pertechnetate were performed if the serum T4 and TSH levels were abnormal. The recall rate was 0.28% and response rate was only 69%. Primary congenital hypothyroidism was diagnosed in 15 infants. Prevalence was 1: 2,484. Among these infants, 8 had ectopic thyroid, 3 had normal glands and 3 were athyrotic. One infant died before the thyroid scan could be performed and did not receive treatment. The median age at initiation of thyroxin therapy was 29 days (range, 20-67 days). The follow up result was satisfactory. This study demonstrated the potential vulnerability of congenital hypothyroid screening program in Thailand. Improvement of parents' education, communication and monitoring should be emphasized for a large screening program.

Multiplex PCR to detect the dystrophin gene deletion in Thai patients.

We have demonstrated the usefulness of the multiplex PCR to directly detect the dystrophin gene mutation. Prenatal diagnosis and confirmation of clinical diagnosis of DMD/BMD via non invasive technique are now possible. Nine DMD and one BMD patients were tested. Five DMD patients demonstrated deletion. Thus, this multiplex PCR could detect deletion in approximately 50 per cent of DMD/BMD Thai patients. Eighty per cent of the deletions were in the distal part, whereas, 20 per cent were in the proximal part. We are planning to establish other molecular techniques such as linkage analysis, cDNA hybridization and immunostaining of dystrophin protein to improve a mode of diagnosis and management of DMD/BMD patients in the Thai community.