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MENTAL RETARDATION AND SPASTIC PARAPARESIS IN FOUR OF EIGHT SIBLINGS
1089 course and absence of similar impairment of renal function in the other A.M.P.S. disorders weighs against this possibility. Other potential causes of the nephrotic syndrome such as lupus erythematosus, lymphoma, or amyloidosis are rare in children, and other symptoms of these diseases undoubtedly would have occurred over the intervening years. Moreover, the nephrotic syndrome is not a complication of the immunodeficiency diseases. It is likely that the unusual and excessive A.M.P.s. excretion, the immune deficit, and the nephrotic syndrome are related in some fundamental way, but the nature of this relationship, and thus the aetiology of this unique syndrome remains obscure.
This work was supported in part by General Clinical Research Centers Program RR-67 and Clinical Pharmacology-Toxicology grant GM-15956.
R. NEIL SCHIMKE
Departments of Medicine and Pediatrics, WILLIAM A. HORTON Kansas University Medical School, Kansas City, Kansas 66103, U.S.A. CHARLES R. KING.
LOW X-CHROMATIN FREQUENCY IN CONGENITAL ADRENAL HYPERPLASIA
SIR,-Dr. Gareis and his colleagues (Aug. 14, p. 373) report low X-chromatin frequency in untreated congenital adrenal hyperplasia. We wish to report another cause of low Barr-body frequency in children with congenital adrenal hyperplasia. In a girl with ambiguous genitalia, the buccal smear stained with aceto-orcein revealed, at 7 days of age, 46% chromatin-positive nuclei. At 10 days of age she began to have vomiting episodes which rapidly led to shock and dehydration. Laboratory investigations confirmed the diagnosis of salt-losing congenital adrenal hyperplasiaserum sodium 127 meq. per litre and potassium 6-4 meq. per litre; urinary 17-ketosteroid excretion 4-2 mg. per 24 hours. At this point the frequency of X-chromatinpositive cells fell to 4-37%. After 4 days of water and electrolyte therapy the Barr-body score was 20%. Karyotyping disclosed a normal 44XX chromosome complement. This observation may be coupled with our previous workdemonstrating a low frequency of X-chromatinpositive cells in serious illnesses of children (involving shock), with return to normal Barr-body scores after improvement of the stress condition. Department of Pædiatrics, University Institute of Medicine, Iasi, Romania.
J. H. SCHNEER AL. NAGHI.
MENTAL RETARDATION AND SPASTIC PARAPARESIS IN FOUR OF EIGHT SIBLINGS
SiR,ŇThis is a brief report of a family in which 4 of 8 siblings exhibit mental retardation and spastic paraparesis. Sibling 2.-A boy, born in 1953. Severe mental retardationStanford-Binet (L.M.) I.Q. 33. Spastic paraparesis (brace on left leg). Had heel-cord lengthening in 1964. Splenectomy for congenital spherocytosis in 1964; no other family members known to have spherocytosis (or histories of early cholelithiasis/ splenectomy). Sibling 5.-A girl, born in 1958. Moderate mental retardation - Stanford-Binet (L.M.) l.Q. 48. Spastic paraparesis. History of seizures in infancy. Bilateral Egger’s procedure, 1968. Partial thyroidectomy for toxic goitre, 1967. Red-blood-cell osmotic fragility normal (1971). Sibling 6.-A boy, born in 1961. Moderate mental retardation Stanford-Binet (L.M.) 1.0. 37. Spastic paraparesis. Heel-cord lengthening, 1969. Red-blood-cell osmotic fragility normal (1971). Sibling 8.-A boy, born in 1964. Mild mental retardationStanford-Binet (L.M.) I.Q. 57. Tight heel cords and hamstrings; 1. 2.
Sanderson, A. R., Stewart, J. L. Br. med. J. 1961, ii, 1065. Schneer, J. H., Naghi, Al. Proc. Pœdiat. Soc. Iasi, February 26, 1971.
stand with heels on floor without flexing and coordination fair. Strabismus. cannot
hips. Balance
All had unremarkable birth histories except sibling 6. The mother was ill for several days in the third month of her pregnancy with him. The father and mother are of normal intelligence, and the academic record of the remaining 4 siblings, 3 girls and a boy, is average or above average. None of the family members with normal intelligence has evidence of neuromuscular disease, nor is there any family history of such conditions. Pineland Hospital and Training Center, Pownal, ROBERT B. ALLPORT. Maine 04069, U.S.A.
IS MENKES’ SYNDROME A HERITABLE DISORDER OF CONNECTIVE TISSUE ?
SIR,-In 1962, Menkes et al.l described a disease characterised by progressive cerebral degeneration with characteristic brain pathology, growth failure, and pili torti (twisted hair) occurring in young boys and inherited as an X-linked recessive trait. The intervening years have produced reports of only 4 further families. 2-5 These reports have added changes in the metaphyses of the long bones and tortuosity of cerebral arteries as features of the syndrome. We have seen 7 boys with this syndrome from 5 families in Melbourne in the past 3 years. There were 7 other affected boys in previous generations of these families. The incidence in Melbourne is estimated to be 1 in 40,000 live births. Hypothermia was an important symptom in most patients, and several babies were acutely ill with septicxmia when they presented. The syndrome may be more frequent than the literature would suggest, because some patients may die undiagnosed. Arterial tortuosity was found radiologically in many major arteries in one patient, but the abnormal arteries were very patchy in distribution in another boy. Stenosis and even complete obliteration of some arteries was found. Microscopical examination of arteries at necropsy showed a very striking fragmentation and splitting of the internal elastic membrane and thickening of the intima in some arteries. Other arteries showed no
abnormality. There is clearly a widespread but patchy degenerative change in the arteries, and it seems reasonable to regard Menkes’ syndrome as another heritable disorder of connective tissue. In searching for the molecule which is basically at fault, the abnormality of the hair must be remembered. The sparing of the fetal hair observed by Wesenberg et al. and confirmed by us may provide a clue. Fibroblastic cells were cultured from 2 patients from different families. Both showed extensive metachromasia in the primary culture when stained with toluidine-blue. This finding lends some further support to the suggestion of a heritable connective-tissue disorder. These findings will be reported in detail elsewhere.
Department of Genetics, University of Melbourne, and Genetics Section, Royal Children’s Hospital Research Foundation, Royal Children’s Hospital. Departments of Pathology and Radiology, Royal Children’s Hospital, Parkville 3052, Australia.
DAVID M. DANKS ELIZABETH CARTWRIGHT.
PETER E. CAMPBELL VALERIE MAYNE.
Menkes, J. H., Alter, M., Steigleder, G. K., Weakley, D. R., Sung, J. H. Pediatrics, Springfield, 1962, 29, 764. 2. Bray, P. F. ibid. 1965, 36, 417. 3. Aguilar, M. J., Chadwick, D. L., Okuyama, K., Kamoshita, S. J. Neuropath, exp. Neurol. 1966, 25, 507. 4. Wesenberg, R. L., Gwinn, J. L., Barnes, G. R. Radiology, 1969, 92, 500. 5. Billings, D. M., Degnan, M. Am. J. Dis. Child. 1971, 121, 447. 1.
This work was supported in part by General Clinical Research Centers Program RR-67 and Clinical Pharmacology-Toxicology grant GM-15956.
R. NEIL SCHIMKE
Departments of Medicine and Pediatrics, WILLIAM A. HORTON Kansas University Medical School, Kansas City, Kansas 66103, U.S.A. CHARLES R. KING.
LOW X-CHROMATIN FREQUENCY IN CONGENITAL ADRENAL HYPERPLASIA
SIR,-Dr. Gareis and his colleagues (Aug. 14, p. 373) report low X-chromatin frequency in untreated congenital adrenal hyperplasia. We wish to report another cause of low Barr-body frequency in children with congenital adrenal hyperplasia. In a girl with ambiguous genitalia, the buccal smear stained with aceto-orcein revealed, at 7 days of age, 46% chromatin-positive nuclei. At 10 days of age she began to have vomiting episodes which rapidly led to shock and dehydration. Laboratory investigations confirmed the diagnosis of salt-losing congenital adrenal hyperplasiaserum sodium 127 meq. per litre and potassium 6-4 meq. per litre; urinary 17-ketosteroid excretion 4-2 mg. per 24 hours. At this point the frequency of X-chromatinpositive cells fell to 4-37%. After 4 days of water and electrolyte therapy the Barr-body score was 20%. Karyotyping disclosed a normal 44XX chromosome complement. This observation may be coupled with our previous workdemonstrating a low frequency of X-chromatinpositive cells in serious illnesses of children (involving shock), with return to normal Barr-body scores after improvement of the stress condition. Department of Pædiatrics, University Institute of Medicine, Iasi, Romania.
J. H. SCHNEER AL. NAGHI.
MENTAL RETARDATION AND SPASTIC PARAPARESIS IN FOUR OF EIGHT SIBLINGS
SiR,ŇThis is a brief report of a family in which 4 of 8 siblings exhibit mental retardation and spastic paraparesis. Sibling 2.-A boy, born in 1953. Severe mental retardationStanford-Binet (L.M.) I.Q. 33. Spastic paraparesis (brace on left leg). Had heel-cord lengthening in 1964. Splenectomy for congenital spherocytosis in 1964; no other family members known to have spherocytosis (or histories of early cholelithiasis/ splenectomy). Sibling 5.-A girl, born in 1958. Moderate mental retardation - Stanford-Binet (L.M.) l.Q. 48. Spastic paraparesis. History of seizures in infancy. Bilateral Egger’s procedure, 1968. Partial thyroidectomy for toxic goitre, 1967. Red-blood-cell osmotic fragility normal (1971). Sibling 6.-A boy, born in 1961. Moderate mental retardation Stanford-Binet (L.M.) 1.0. 37. Spastic paraparesis. Heel-cord lengthening, 1969. Red-blood-cell osmotic fragility normal (1971). Sibling 8.-A boy, born in 1964. Mild mental retardationStanford-Binet (L.M.) I.Q. 57. Tight heel cords and hamstrings; 1. 2.
Sanderson, A. R., Stewart, J. L. Br. med. J. 1961, ii, 1065. Schneer, J. H., Naghi, Al. Proc. Pœdiat. Soc. Iasi, February 26, 1971.
stand with heels on floor without flexing and coordination fair. Strabismus. cannot
hips. Balance
All had unremarkable birth histories except sibling 6. The mother was ill for several days in the third month of her pregnancy with him. The father and mother are of normal intelligence, and the academic record of the remaining 4 siblings, 3 girls and a boy, is average or above average. None of the family members with normal intelligence has evidence of neuromuscular disease, nor is there any family history of such conditions. Pineland Hospital and Training Center, Pownal, ROBERT B. ALLPORT. Maine 04069, U.S.A.
IS MENKES’ SYNDROME A HERITABLE DISORDER OF CONNECTIVE TISSUE ?
SIR,-In 1962, Menkes et al.l described a disease characterised by progressive cerebral degeneration with characteristic brain pathology, growth failure, and pili torti (twisted hair) occurring in young boys and inherited as an X-linked recessive trait. The intervening years have produced reports of only 4 further families. 2-5 These reports have added changes in the metaphyses of the long bones and tortuosity of cerebral arteries as features of the syndrome. We have seen 7 boys with this syndrome from 5 families in Melbourne in the past 3 years. There were 7 other affected boys in previous generations of these families. The incidence in Melbourne is estimated to be 1 in 40,000 live births. Hypothermia was an important symptom in most patients, and several babies were acutely ill with septicxmia when they presented. The syndrome may be more frequent than the literature would suggest, because some patients may die undiagnosed. Arterial tortuosity was found radiologically in many major arteries in one patient, but the abnormal arteries were very patchy in distribution in another boy. Stenosis and even complete obliteration of some arteries was found. Microscopical examination of arteries at necropsy showed a very striking fragmentation and splitting of the internal elastic membrane and thickening of the intima in some arteries. Other arteries showed no
abnormality. There is clearly a widespread but patchy degenerative change in the arteries, and it seems reasonable to regard Menkes’ syndrome as another heritable disorder of connective tissue. In searching for the molecule which is basically at fault, the abnormality of the hair must be remembered. The sparing of the fetal hair observed by Wesenberg et al. and confirmed by us may provide a clue. Fibroblastic cells were cultured from 2 patients from different families. Both showed extensive metachromasia in the primary culture when stained with toluidine-blue. This finding lends some further support to the suggestion of a heritable connective-tissue disorder. These findings will be reported in detail elsewhere.
Department of Genetics, University of Melbourne, and Genetics Section, Royal Children’s Hospital Research Foundation, Royal Children’s Hospital. Departments of Pathology and Radiology, Royal Children’s Hospital, Parkville 3052, Australia.
DAVID M. DANKS ELIZABETH CARTWRIGHT.
PETER E. CAMPBELL VALERIE MAYNE.
Menkes, J. H., Alter, M., Steigleder, G. K., Weakley, D. R., Sung, J. H. Pediatrics, Springfield, 1962, 29, 764. 2. Bray, P. F. ibid. 1965, 36, 417. 3. Aguilar, M. J., Chadwick, D. L., Okuyama, K., Kamoshita, S. J. Neuropath, exp. Neurol. 1966, 25, 507. 4. Wesenberg, R. L., Gwinn, J. L., Barnes, G. R. Radiology, 1969, 92, 500. 5. Billings, D. M., Degnan, M. Am. J. Dis. Child. 1971, 121, 447. 1.