H. D. Bakker - M. Westra - W. C. G. Overweg-Plandsoen - G. van Waveren - J. H. Sillevis Smitt - N. G. G. M. Abeling - R. J. A. Wanders - R. B. H. Schutgens - A. H. van Gennip.
Received: 10 February 1993
Accepted: 21 January 1994
Normalisation
of severe cranial CT scan abnormalities
after biotin in a case of biotinidase deficiency
Sir: Cranial CT scan abnormalities in biotinidase deficiency
include cerebral oedema, atrophy and basal ganglia calcifications [4]. We present
a case with early onset of the symptoms of biotinidase deficiency and distinct
cranial CT scan abnormalities at the age of 5 weeks.
The patient, a boy, was born after an uneventful pregnancy and delivery, as
the second child of healthy unrelated parents. Birth weight 3800 g, length 53
cm.
He was breast-fed and had no problems until 2.5 weeks of age. Subsequently he
gradually developed alopecia, desquamation of the skin, lethargy and tremors.
At the age of 5 weeks he was admitted to the Children' 5 Academic Hospital with
hypothermia (340 C), lethargy, muscular hypotonia, convulsions with athetoid
movements, diffuse thinning of the scalp hair and lamellar scaling of the skin,
in particular on the scalp and in the axillary and inguinal areas. EEG was normal,
but the CT scan of the brain showed severe hypodensity of the white matter (Fig.
la). The urinary organic acid profile was characteristic of multiple carboxylase
deficiency, except for an unexplained moderate amount of 2-hydroxyglutaric acid.
Serum biotinidase activity was virtually undetectable in the patient, while
his parents had activities in the heterozygous range. Medication with biotin
(10 mg/day) resulted in a dramatic improvement. No further convulsions occurred
and the neurological abnormalities disappeared within I week. The skin lesions
recovered gradually and became undetectable within 3 weeks. After 6 weeks of
treatment the CT scan of the brain was nearly normal with only slight signs
of atrophy. Six months thereafter and at the age of 14 months the CT scans of
the brain appeared to be normal, except for slightly enlarged frontal horns
of the ventricles (Fig. lb). On clinical examination at that time mental development,
acoustic brainstem evoked response and visual evoked response were normal but
signs of spastic diplegia had not completely disappeared. At the age of 32 months
he is a normal, healthy boy with only walking problems by an endorotation position
of both lower legs. There is no clear relationship between the severity of CT
scan abnormalities and clinical symptoms in patients with biotinidase deficiency
[3, 6]. Biotinidase activity is needed to liberate biotin from biocytin and
biotinyl peptides. The cerebral nervous system pathology in biotinidase deficiency
may result from the toxic effect of accumulation in the cerebrospinal fluid
of biocytin [1, 6] and biotinyl peptides, and/or lactate [5].
Previous report of cranial CTs in patients with biotinidase deficiency did not
mention abnormalities in all cases [3, 6, 7]. As far as we know there is only
one case with cerebral oedema at the age of 4 weeks [2]. We report the first
case with diffuse hypodensity of the white matter as an early lesion. This finding
and the prompt recovery early on biotin treatment illustrate the importance
of rapid diagnosis and treatment of patients with biotinidase deficiency.
Fig. 1 a, b CT scans of the brain at different ages.a. CT scan performed at the time of diagnosis (6 weeks of age). Note the hypodensity of the white matter. b. CT scan performed at the age of 14 months (more than 1 year of treatment with biotin). No hypodensity of the white matter; slightly enlarged frontal horns of the ventricles
References
1) Daimantopoulos N, Painter MJ,
Wolf B, et al (1986) Biotinidase deficiency: accumulation of lactate
in the brain and re sponse to physiologic doses of biotin. Neurology 36:1107-1109
2) Ureter J, Holme E, Lindstedt S, et al (1985) Biotin-responsive
methyl-crotonyl-glycinuria with biotinidase deficiency. J Inherited Metab Dis
8 [Suppl 2]: 103-104
3) Mitchel G, Ogier H, Munnich A, et al (1986) Neurological deterioration
and lactic acidemia in biotinidase deficiency Neuropediatrics 17:129-131
4) Schulz PE, Weiner SP, Belmont JW, et al (1988) Basal ganglia
calcifications in a case of biotinidase deficiency. Neurology 38:1326-1328
5) Suchy SF, Secor-McVoy J, Wolf B (1985) Neurologic symptoms
of biotinidase deficiency: possible explanation. Neurology 35:1510-1511
6) Wolf B, Grier RE, Allen RJ, et al (1983) Phenotypic variation in biotinidase
deficiency. J Pediatr 103 :233-237
7) Wolf B, Heard US, Weissbecker KA, et al (1985) Biotinidase deficiency:
initial clinical features and rapid diagnosis. Ann Neurol 18:61-617
ADRES :
H. D. Bakker. M. Westra W. C.G. Overweg-Plandsoen
J. H. Sillevis Smitt N. G. G.M. Abeling R. J. A. Wanders . R. B. H. Schutgens
A. H. van Gennip :
Academic Medical Centre,
Divisions of "Emma Kinderziekenhuis",
Children's AMC and Clinical Chemistry,
Meibergdreef 9, NL-l 105 AZ Amsterdam
The Netherlands
G. van Waveren
Boven IJ Ziekenhuis,
Department of Paediatrics,
Amsterdam, The Netherland