Search

Multiple carboxylase deficiency (MCD) is an autosomal recessive metabolic disorder caused by defective activity of biotinidase or holocarboxylase synthetase (HLCS) in the biotin cycle. Clinical symptoms include skin lesions and severe metabolic acidosis. Here, we reported four unrelated Thai patients with MCD, diagnosed by urine organic acid analysis. Unlike Caucasians, which biotinidase deficiency has been found to be more common, all of our four Thai patients were affected by HLCS deficiency. Instead of the generally recommended high dose of biotin, our patients were given biotin at 1.2 mg/day. This low-dose biotin significantly improved their clinical symptoms and stabilized the metabolic state on long-term follow-up. Mutation analysis by polymerase chain reaction-sequencing of the entire coding region of the HLCS gene revealed the c.1522C>T (p.R508W) mutation in six of the eight mutant alleles. This suggests it as the most common mutation in the Thai population, which paves the way for a rapid and unsophisticated diagnostic method for the ethnic Thai. Haplotype analysis revealed that the c.1522C>T was on three different haplotypes suggesting that it was recurrent, not caused by a founder effect. In addition, a novel mutation, c.1513G>C (p.G505R), was identified, expanding the mutational spectrum of this gene.

Mutations in the TBX22 gene underlie an X-linked malformation syndrome with cleft palate (CP) and ankyloglossia. Its mutations also result in non-syndromic CP in some populations. To investigate whether mutations in TBX22 play a part in the formation of non-syndromic CP in the Thai population, we performed mutation analysis covering all the coding regions of the TBX22 gene in 53 unrelated Thai patients with non-syndromic CP. We identified four potentially pathogenic mutations, 359G-->A (R120Q), 452G-->T (R151L), 1166C-->A (P389Q), and 1252delG in four different patients. All mutations were not detected in at least 112 unaffected ethnic-matched control chromosomes and had never been previously reported. R120Q and R151L, found in two sporadic cases, were located in the DNA binding T-box domain. P389Q and 1252delG, found in two familial cases, were at the carboxy-terminal region, which has never been described. Our study indicates that TBX22 mutations are responsible for a significant proportion of Thai non-syndromic CP cases confirming its importance as a frequent cause of non-syndromic CP across different populations.

Infantile cortical hyperostosis (ICH) is an inherited disorder characterized by hyperirritability, acute inflammation of soft tissues, and massive subperiosteal new bone formation. It typically appears in early infancy and is considered a benign self-limiting disease. We report a three-generation Thai family with ICH, the oldest being a 75-year-old man. A heterozygous mutation for a 3040C-->T in exon 41 of COL1A1 was found in affected individuals, further confirming the autosomal dominance of Caffey disease that is caused by this particular mutation. The novel findings in our studies include short stature and persistent bony deformities in the elderly. The height mean Z-score of the five affected individuals was -1.75, compared to 0.53 of the other seven unaffected individuals giving a p-value of 0.008. Short stature may be partly due to progressive height loss from scoliosis, compression fractures of the spine and genu varus. These features, which have not previously been described, expand the phenotypic spectrum of the Caffey disease.