Sibs with Mental and Physical Retardation and Trichorrhexis Nodosa with Abnormal Amino Acid Composition of the Hair
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Arch Dis Child: first published as 10.1136/adc.43.228.211 on 1 April 1968. Downloaded from Arch. Dis. Childh., 1968, 43, 211. Sibs with Mental and Physical Retardation and Trichorrhexis Nodosa with Abnormal Amino Acid Composition of the Hair R. J. POLLITT,* F. A. JENNER,* and MARGARET DAVIES From Medical Research Council Unit for Research on the Chemical Pathology of Mental Disorders, Medical School, Birmingham 15; Hollymoor Hospital, Birmingham 31; and Lea Castle Hospital, Wolverley, Nr. Kidderminster, Worcestershire Trichorrhexis nodosa is a condition in which Her tongue was reported to have white plaques. She individual hairs develop areas where the shaft has was at first thought to be suffering from the effects of split longitudinally into numerous small fibres. cerebral anoxia at birth, which had caused brain damage, The hairs eventually break at these points leaving and the mother was therefore reassured about further pregnancies. brush-like ends. Usually trichorrhexis nodosa The patient was admitted for special studies in May results from mechanical trauma or harsh chemical 1966 aged 5 years. She was now a simple, fairly good- treatment (Chernosky and Owens, 1966), but two natured child, with an obviously vacant expression. inherited disorders, argininosuccinic aciduria (Allan She looked perhaps three years younger than her age. et al., 1958; Levin, Mackay, and Oberholzer, 1961; She was affectionate, was walking, and was feeding copyright. Westall, 1960) and a type of sex-linked neuro- herself, but remained incontinent. She weighed 15-5 degeneration (Menkes et al., 1962), areoftenassociated kg., her head circumference was 47 cm., and her body with a very marked degree of trichorrhexis nodosa. length was 91 cm. This is a report of a brother and sister with another No formal psychological testing was possible because of the short attention span. Her motor development syndrome, showing mental and physical retardation, was within the range of 18 months to 2 years. She had trichorrhexis nodosa, and other hair defects. a wide-stanced gait, but could climb on to a chair. She could hold two cubes in one hand and return them to a Case Reports container but not build with them. She could extend http://adc.bmj.com/ her arm to help when being dressed. The two children are the second and third of a family Her speech and understanding were at a level below of three. The parents were unrelated, and appear that expected of a child aged 1 year. There was no normal. The father, a farm worker, was born in 1936, recognizable speech. and the mother in 1938. The mother's brother had She had short sparse eyebrows, and the scalp hair was Down's syndrome, but he died suddenly in 1965; no 1-2 cm. long, except for areas cf alopecia caused by chromosome studies had been performed. The first rubbing (Fig. la). Apparently the hair condition had child is a normal intelligent boy (N.C.) born in 1959. been progressively deteriorating, though with short remissions, since she was about 1 year old. The hair had on October 2, 2021 by guest. Protected Case 1. The second child (L.C.) was born in May a matted appearance and there was a follicular hyper- 1961; her birthweight was 3 0 kg., body length 48 cm., keratosis of the scalp and forehead. and head circumference 33 cm. The mother had The hair itself could easily be broken and showed toxaemia ofpregnancy, a severe antepartum haemorrhage, classical trichorrhexis nodosa (Fig. 2a). In addition the and the labour and delivery were long and difficult; in shaft was often flattened in cross-section and sometimes addition the child is reported to have been severely twisted slightly in the long axis (pili torti). The hair jaundiced for 10 days after her birth. She was not surface was irregular, and scanning electron micrographs noted to be abnormal until 1 year old, when she showed showed that the normal pattern of scales was almost no signs ofwanting to stand or walk. She was obviously completely absent (Fig. 3). The high-angle x-ray retarded, and in addition her hair was sparse, stubbly, diffraction pattern was normal, but electron-microsco- and brittle. Her nails were ill-shapen and spoon-like. pical examination of stained sections has shown several Received August 7, 1967. abnormalities (Sikorski and Robson, 1968). * Present address: The University Department of Psychiatry, She had cold blue extremities indicating a defective Whiteley Wood Clinic, Shefficld S10 3TL. peripheral circulation, but examination, including ECG, 211 Arch Dis Child: first published as 10.1136/adc.43.228.211 on 1 April 1968. Downloaded from 212 Pollitt, Jenner, and Davies * 1; . (a) (b) FIG. 1.-(a) Case 1, aged 51 years and (b) Case 2, aged 3 years. failed to reveal any other cardiovascular defects. The the 5th centile (Gordon, 1966). The sella turcica was child was not hypotonic and examination of the central bridged and small in size, the lateral area 40 sq.cm., and copyright. nervous system was normal. the sella index 1-4. The long bones and the bones of the hands and feet showed ossification compatible with Radiological studies. Skull was short based, with a bone age of 1-1I years; there were a number ofdisturbed small vault (1175 ml. cranial capacity) approximately at growth lines in the metaphyses. http://adc.bmj.com/ on October 2, 2021 by guest. Protected (a) (D) FIG. 2.-Light microscope photographs of the untreated hair. (a) Case 1; (b) Case 2. Arch Dis Child: first published as 10.1136/adc.43.228.211 on 1 April 1968. Downloaded from Sibs with Mental and Physical Retardation and Trichorrhexis Nodosa 213 (aZ) (bhi FIG. 3.-Stereoscan electromicrographs of hair (a) from Case 1 and (b) from a control subject. Dental studies. The enamel of the teeth, though The amino acids were present in normal amounts; in intact, was thin. Aged 5 the deciduous teeth had particular, the level of glutamic acid was not raised, and completely erupted and permanent dentition was well cystine was present. advanced. She displayed marked bruxism. CSF was deproteinized with picric acid, desalted, and subjected to thin-layer chromatography as before. The Chromosome studies. Buccal smears were of normal following amino acids presented clearly defined spots in copyright. female type, and seven cells from a lymphocyte culture all descending order of intensity-glutamine, alanine, contained 46 chromosomes and a normal female karyo- glycine, serine, leucines, glutamic acid, aspartic acid, type. Dermatoglyphs were normal. lysine, phenylalanine, valine, histidine, threonine, arginine, cystine, and asparagine. Proline was also Electroencephalogram. Non-specific abnormalities, present but not easily compared with the other amino with a paucity of faster rhythmic activity and an excess acids. of slow components; there was no asymmetry. Faecal amino acids, examined by high-voltage electro- Urinanalysis, serum pro- phoresis, showed a normal pattern. Laboratory investigations. http://adc.bmj.com/ teins, and electrophoresis, serum cholesterol, electrolytes, Whole blood -SH group levels determined by Ellman's uric acid, bilirubin, alkaline phosphatase, zinc sulphate (1959) method were within the normal range. precipitation test, thymol turbidity, and flocculation Chemistry of hair. A specimen ofhair was hydrolysed tests, SGPT, calcium, fibrinogen, blood urea, blood in a sealed tube with 6N-hydrochloric acid and the caeruloplasmin, ESR, Hb, red cell count, white cell resultant amino acids examined by 2-dimensional count, platelet count, steroids, and pH were normal. and There was no CSF showed no abnormalities of cell content, glucose, electrophoresis chromatography. protein, chloride, or colloidal gold precipitation tests. trace of argininosuccinic acid or of its cyclic anhydrides (Westall, 1960; Ratner and Kunkemueller, 1966). It on October 2, 2021 by guest. Protected The serum inorganic phosphate was 4 * 8 and 5 25 mg./ was noticed, however, that the proportions of the amino 100 ml., outside the laboratory's range of2-4 mg./100 ml. acids were different from those from a sample of normal Urinary phenolic acids after a plant-free diet were hair so treated. The amino acid compositions of the normal. The urinary amino acids were examined by hydrolysates were determined quantitatively on an high-voltage electrophoresis at pH 2 * 0, followed by amino acid analyser (Table I). chromatography in the second dimension using butanol- The low cystine content was confirmed using the acetic acid-water (12: 3: 5). Argininosuccinic acid Shinohara (1936) method, and specific chromatographic (Koch-Light Laboratories Ltd.) was also run as a searches by Dr. D. J. Raven failed to reveal possible standard. The pattern was normal; in particular, the such as acid and lanthionine. cystine spot was of usual size and there was no trace of degradation products cysteic argininosuccinic acid. Plasma amino acids were exa- mined by 2-dimensional thin-layer chromatography Case 2. A.C. was born in Janualy 1964, weighed using systems I and II of von Arx and Neher (1963), 3 130 kg., his body length was 48 cm.; he was cyanosed after deproteinizing by picric acid or by gel filtration on at birth and had a considerable ventricular septal defect. Sephadex G25 and desalting on Dowex 50x8 resin. At 5 weeks, he had a folliculitis of his face and scalp: Arch Dis Child: first published as 10.1136/adc.43.228.211 on 1 April 1968. Downloaded from 214 Pollitt, Jenner, and Davies TABLE I tion. An amino acid analysis of his hair is given in Amino Acid Analyses of Hair and Hair Proteins: Table I. Results expressed as g. nitrogen per 100 g. nitrogen Table II gives the family blood groupings and recovered from column (ammonia excluded) confirms the reported relationships. Discussion Low- High- Case 1 Case 2 Control sulphur sulphur The only clear-cut biochemical abnormality Protein* Protein t demonstrated so far in these 2 patients is in the Asp .