Trichothiodystrophy: quantification of cysteine in human hair and nails by application of sodium azide-dependent oxidation to cysteic acid

Abstract

The term "trichothiodystrophy" (TTD) covers several autosomal recessive diseases whose diagnostic hallmark is short, brittle hair low in sulfur and cystine because of impaired synthesis of high-sulfur matrix protein. Clinical symptoms associated with TTD represent a variable range of abnormalities in organs derived from ectoderm and neuroectoderm. Important laboratory tests of the hair for the diagnosis of TTD comprise polarizing microscopy ("tiger-tail" pattern), electron microscopy, and amino acids analysis of hydrolyzed hair with a special focus on cystine. However, only very few institutions determine the amino acid composition of human hair and nail clippings, which requires special sample preparation including hydrolysis. If no special precautions are taken, quantification of cysteine and cystine becomes inaccurate because of decomposition of these residues during hydrolysis. We therefore performed the sample work-up with azide-dependent oxidation which we have for the first time adapted for analysis of hair and nail clippings. With our control and parent data resembling published data on hair and nail samples, we obtained a decreased proportion of cysteine (half cystine, determined as cysteic acid) in materials obtained from a boy with TTD. Clearly, the method for the quantification of cysteine following sodium azide-dependent oxidation is a suitable and rather convenient approach to the quantification of cyst(e)ine and other amino acids in hair and nail proteins, and is a valuable contribution to the diagnosis of TTD.

Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations

“…The cause of death was pneumonia or other infection (especially sepsis) for 13 of these patients (fig 3). 40 41 63 74 85 90 91 94 98 99 107 One additional patient85 died at 12 months after developing a fever, despite antibiotic use. The remaining patients died of drowning,62 cachexia and dehydration,98 respiratory failure,46 or a sudden or unexpected death 32 68.…”

“…Thirteen patients had brittle or abnormal hair. There were 14 patients (13%) reported to have short birth length22 34 40 45 68 70 81 85 98 99 106 and eight patients (7%) to have small birth head circumference 40 85 98 99 106. Values for birth length were given for 18 patients, ranging from 36–51 cm, with a median of 46 cm.…”

“…In addition, one pregnancy85 was reported as having an abnormal prenatal screening test (elevated maternal serum α-fetoprotein). There were 13 cases of caesarean section and four cases of breech presentation 57 73 99 108. The caesarean sections were performed secondary to both maternal indications (five cases) and fetal indications (eight cases).…”

Inherited ichthyoses/generalized Mendelian disorders of cornification

“…[45][46][47] In addition, light microscopy of hair shafts demonstrates 'bamboo hairs' (trichorrhexis invaginata) in NS (Figure 1j) 48 and polarization microscopy of TTD patient hairs reveals a tiger-tail pattern that corresponds to the diagnostic low sulfur protein content (Figure 1i). 49,50 Electron microscopy. Electron microscopy helps to narrow down the list of differential diagnoses or even rules out certain types of MeDOC.…”

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

“…Methionine: Precursor of glutathione (200) ; precursor of S-adenosyl methionine (653) ; neural tube defects (654) ; colon cancer (410) ; cognitive impairment in situation of folate deficiency (653) ; antioxidant activity (655) ; lipotrope (239) Cystine: Hair and nail development (656,657) ; muscle wasting (658) ; antioxidant and cell signalling through reactive cysteine residues in proteins (659) Total fibre (18,46,58,266,660,661) :…”