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Trichothiodystrophy
Trichothiodystrophy or TTD,
as it is concisely mentioned, is a heterogeneous group of autosomal
recessive disorders, characterized by abnormally sulfur deficient brittle
hair and accompanied by ichthyosis and other manifestations. In TTD
patients, the hair appear dry, short and sparse, and the ones already
existing splits longitudinally in to small fibers, the viscoelastic
parameters of hair being compromised compared to controls.
Inside the range of TTD syndrome
are numerous interrelated neuroectodermal disorders. The Trichothiodystrophy
syndromes are invariably characterized by the defective synthesis of
high-sulfur matrix proteins. Half of the patients show abnormalities
in nucleotide excision repair (NER) of ultraviolet damaged DNA.
In fact, three categories are
recognized on the basis of cellular responses to UV damage and the affected
gene. Most patients show mutations on the two alleles of the XPD gene.
In UV-sensitive TTD patients, the TFIIH transcription factor containing
XPB and XPD helicase activities necessary for both transcription initiation
and DNA repair are found to be damaged. Beyond deficiency in the NER
pathway, basal transcription is altered leading to decreased transcription
of specific genes.
TTD patients generally have
an unusual facial appearance, marked by protruding ears and receding
chin, and retarded overall growth. The growth retardation, neurological
abnormalities and brittle hair and nails are attributed to the depressed
RNA synthesis in TTD patients.
Light microscopy on TTD patients reveals trichosis of hair and an irregular hair surface and diameter. But a nodal appearance and decreased cuticular layer with twisting may be misleading and may closely mimic trichorrhexis nodosa. Also, when the patient’s hair is viewed under polarized light, it shows alternate light and dark bands giving a strand a ‘tiger-tail’ appearance. But it has been noticed recently that such ‘tiger-tail’ patterns are also found in healthy infants. Hence the amino acid analysis quantitating sulfur levels remains a reliable test for TTD.