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Sphingomyelin of Red Blood Cells in Lipidosis and in Dementia of Unknown Origin in Children

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Sphingomyelin of Red Blood Cells in Lipidosis and in Dementia of Unknown Origin in Children Arch Dis Child: first published as 10.1136/adc.44.234.197 on 1 April 1969. Downloaded from Arch. Dis. Childh., 1969, 44, 197. Sphingomyelin of Red Blood Cells in Lipidosis and in Dementia of Unknown Origin in Children G. J. M. HOOGHWINKEL, H. H. VAN GELDEREN, and A. STAAL From the Laboratory of Medical Chemistry and the Departments of Paediatrics and Neurology, University of Leiden, The Netherlands Histological and chemical examinations of biopsy no diagnosis could be made, are briefly described in specimens from cerebral tissue of children suffering Table I. Incomplete investigation made it impossible to from undiagnosed progressive brain disease are reach a diagnosis in Cases 7 and 8. The molar con- performed increasingly. Important information centrations of phospholipids in the red blood cells therapeutic have been determined as described by Hooghwinkel is provided, which, though rarely of and Niekerk (1960), Hooghwinkel and Borri (1964), value, does increase precision of diagnosis, and Hooghwinkel, Borri, and Bruyn (1966). The prognosis, and genetic advice (Cumings, 1965a, amounts of the various phospholipids of red blood b, c; Poser, 1962; Adams, 1965). This is especially cells have been expressed as molar percentages of true of the chemical investigations, and it is likely total phospholipids. Absolute values of phospho- that chernical analyses will challenge the current lipids depend a good deal on size and shape of the classifications of progressive brain disease. Amaur- otic idiocy has already proved to be more hetero- 36 copyright. 0 geneous than was thought hitherto, while supposedly -a .A a different diseases, such as Niemann-Pick's and 0 34 . -0 - - - - - +- gargoylism, have more in common than earlier ..10- classifications suggested. 0- 5 ~~~~~~~~~0 However, brain biopsy is still a procedure not q~ - to be undertaken lightly, and it would be an advan- 32 tage if comparable information could be gained by 0 .0 a less drastic method. We have been interested -C 30- --§-------I-------.--- http://adc.bmj.com/ in the possibility of finding abnormalities in easily °°O + 'accessible tissue, such as red blood cells, which 0~ I might correlate with abnormalities in the constitu- 28 . tion of the brain. In this paper we give the results 0 of a study of the sphingomyelin content of ery- x E throcytes in children with various types of pro- 0 26- gressive brain disease. cr <C I0IIIII IV V VI on October 2, 2021 by guest. Protected 24 Material and Methods I II ~III IV V VI The patients included in this study are enumerated in the legend to the Fig. Nearly all were more than FIG.-Sphingomyelin of red blood cells, as a percentage 2 years old. The group of children with juvenile ofphospholipids, in six groups of cases. amaurotic idiocy came from different hospitals; in only was histo- I: normal values, 17 cases ( 0: < 8 years; *: > 10 some of these cases the diagnosis verified by years), mean ±2SD; II:juvenile amaurotic idiocy, 12 cases; logical and biochemical investigation of brain tissue. III: mucopolysaccharidosis, 7 cases; IV: other diagnoses All the other patients were under our care, the diagnosis Gaucher's 3 being verified in nearly all by means of biopsies. (o, disease, cases; x, Niemann-Pick's The 10 patients with progressive brain disease disease, 2 cases; o, sudanophilic leucodystrophy, 1 case; in which *, metachromatic leucodystrophy, 1 case); V: dementia (dementia and neurological abnormalities), of unknown cause, 10 cases; VI: controls with severe Received August 26, 1968. cerebral atrophy after brain damage in early life. 197 5 Hooghwinkel, van Gelderen, and Staal Arch Dis Child: first published as 10.1136/adc.44.234.197 on 1 April 1969. Downloaded from TABLE Details of Patients with Age at Time of Physical and Case Sex Development and Investi- Family History Neurological Symptoms Ocular Symptoms No. ProgressionParny of Disease gation and Signs* (yr.) ,. ,~- 1 I F Normal till 11 yr.; then 3 Negative No recognition; severely Vision uncertain; otherwise gradual dementia mentally retarded, normal spastic tetraplegia, irregular myoclonic jerks, fine head tremor 2 M Slow till 5 yr.; then gradual 10 Negative Functioning at IQ 30 Bilateral cataract; fundus but progressive dementia (2 yr. later completely probably normal IM demented); coarse features but neither hepatomegaly nor bone abnormalities; myoclonic jerks; spastic tetraplegia; PEG, diffusely enlarged ventricles 3 F Normal till 4 mth.; then 6 Brother died from similar Completely demented; Bilateral cataract, probably rapid dementia illness, no diagnosis spastic legs; PEG, blind made synmmetrically enlarged ventricles 4 F Normal till 6 mth.; then 21 Negative Severely demented, None severe regression hyperkinesis, convulsions, abnormal copyright. postures; PEG, cortical atrophy rt. frontal area 5 F Normal till 9 mth.; then Nearly Negative Severely demented, None rapid regression 2 primitive reflexes, spastic tetraplegia; fever of unknown cause 6 M Normal in first few mth.; 4 3 of 5 sibs mentally Severely retarded but Pigment increase then slow development retarded, with retinal motor development abnormalities and reasonable; nystagmus, liver enlargement liver much enlarged; http://adc.bmj.com/ PEG, slight increase of ventricle size 7 F Normal till 3 mth.; then 1 .1 Negative Completely demented, None rapid dementia with spastic tetraplegia, epilepsy probably blind, frequent convulsions 8 M Normal till 6 mth.; then 1 Consanguineous parents; Retarded, loss ofcontact; Tapetoretinal rapid regression maternal brother died vision reduced, degeneration in infancy from stereotypic aimless convulsions and head movements; PEG, on October 2, 2021 by guest. Protected enlargement cerebral atrophy 9 M Normal till 7 yr.; failing 14 Insufficient data; ataxiain Ataxy, loss of co-ordina- None at school; from 9 yr. paternal family ? tion; enlargedliver increasingly atactic with and spleen; normal acid petit-mal epilepsy; phosphatase intellectual functions declined; IQ 100 at 7yr.;49at 14yr. M Normal till 5 yr.; then 8 Negative Physical and neurological Except for myopia no decline ofmental examination normal; abnormalities functions without other PEG, slightly enlarged serious signs ventricles; psychologist, dementing, organic l- picture, IQ 55 (88 2 yr. before) t TLC = thin-layer * * PEG-pneumoencephalogram. PEG = pneumoencephalogram. t TLC = thin-layer chromatography.~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~chromatography. Arch Dis Child: first published as 10.1136/adc.44.234.197 on 1 April 1969. Downloaded from Sphingomyelin of Red Blood Cells in Lipidosis and in Dementia of Unknown Origin 199 I 'Dementia of Unknown Origin I Biopsy Sphingomyelin EEG (i% of P-lipids Diagnosis in erythrocyte) Tissue Histology Chemistry No normal background 29-4 Brain No abnormalities Moderate decrease of Dementia ofunknown activity, periodic bursts myelinlipids in origin, with spastic ofhigh-voltage delta white matter, paraplegia and waves sphingomyelin myoclonic jerks moderately decreased in white matter, strongly decreased in grey matter Almost continuously 28 0 Brain Typical picture of Decrease ofmyelin Dementia ofunknown spike-and-wave activity amauroticidiocy; lipids; decrease of cause; probably many neuronal cells sphingomyelin agangliosidosis; and a number of content ofwhite much increased glia cells swollen matter; marked urinary excretion withPAS +ve increase of ofacid mucopoly- material gangliosides (G5 saccharides and G6) on chromatography Severe diffuse abnormalities 29-7 Brain Focal perivascular Slight decrease of Familial dementia of most prominent in rt. necrosis with myelinlipids and unknown origin hemisphere gliosis around moderate decrease these areas ofsphingomyclin Bilateral spikes and 30-1 Brain No abnormalities Decrease of Dementia ofunknown waves, sometimes sphinogomyelinin origin synchronous grey and white copyright. matter; generalized decrease ofmyelin lipids No abnormalities, but at 31-4 Rectal mucosa; No abnormalities Not done Dementia of unknown age 4 yr. cerebral activity suralis nerve origin; normal much diminished brain one Hortega glia sphingomyelin in cellinfiltration red cells Isolated theta and delta 26-3 Liver Specimen lost Almost complete Familial oculo- waves ofspikey character absence of cerebral syndrome, in rt. temporal area sphingomyelin with with visceral long fatty acid involvement; chains investigations of http://adc.bmj.com/ patient and sibs incomplete Severe generalized 29 9 Dementia ofunknown epileptic activity origin; cerebral biopsy planned Normal 26-8 Oculo-cerebral syndrome of unknown origin, low sphingomyelin in RBC, hence on October 2, 2021 by guest. Protected amauroticidiocy unlikely Slow background activity; 29-1 Lymph-node; Foam cells Cholesterol much Clinically no specific abnormalities bone-marrow; Foam cells increased; suggestive of liver Foam cells sphingomyelin only Niemann-Pick's slightly increased; disease, but normallipid chemical analysis hexose content; ofliver specimen TLCt did not against this show increase of glycolipid Diffusely abnormal; 29-7 Sural nerve Normal Dementia of unknown paroxysmal activity origin, too well to on photo-stimulation justify brain biopsy Arch Dis Child: first published as 10.1136/adc.44.234.197 on 1 April 1969. Downloaded from 200 Hooghwinkel, van Gelderen, and Staal TABLE II Molar Distribution of Phospholipids, Expressed as Percentage of Total Phospholipid, in Red Blood Cells (mean and range) Lysophosphatidylcholine Sphingomyelin plus Phosphatidylethanolamine
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