Vol 44 # 2 June 2012 - Kma.org.kw

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Spinal Cord Demyelination in Biotinidase Deficiency: A Case Report
June 2012
Table 1: Biotinidase deficiency myopathy or spinal cord lesion [7,12,13]
Index patient
Ref [12]
Ref [13]
Case 1 [7]
Case 2 [7]
Clinical presentation
Age of onset
Ataxia
Dysathria
Seizure
Skin rash
Alopecia
Weakness
Laboratory Findings
Abnormal urine for
organic acids
Lactic acidosis
S. Ammonia
MRI Spinal cord
Nerve conduction, EMG
26 months
+
-
-
+
+
+
-
+
Normal
Abnormal signal of
spinal cord white
matter
ND
18 months
+
+
-
+
+
-
+
-
NA
Abnormal signal of
spinal cord white
matter
N
36 months
+
NA
-
-
+
+
+
+
Elevated
Abnormal signal of
spinal cord white
matter
NA
7 1 ⁄ 2
yrs
-
-
-
+
-
+
+
+
NA
Abnormal signal of
spinal cord white
matter
Abnormal(↓ motor
conduction velocity)
5 yrs
+
NA
-
+
+
+
+
+
Normal
Abnormal signal
of spinal cord
white matter
NA
+: present, -: absent, NA: not available, ND: not done, NCV: nerve conduction velocity, ↓: decreased
Biochemical finding are variable and often reveal
hyperammonemia, raised lactic acid concentrations
in blood or cerebrospinal fluid and abnormal urinary
organic acid excretion, especially, increase in 3-
hydroxyisovaleric acid, B-methylcrontonylglycine, B-
hydroxypropionate and methyl citrate.
There are two enzyme deficiencies that cause
multiple carboxylase deficiencies.Theoneisbiotinidase
which is responsible for recycling of endogenous
biotin [1,8] and the other is holocarboxylase synthetase
deficiency which prevents the attachment of biotin to
apocarboxylase [1,9] .
The disease can be diagnosed by a flourimetric or
colorimetric enzyme assay in serum. The locus of the
biotinidase gene has been mapped to chromosome
3 in band p25. First trimester prenatal diagnosis for
biotinidase deficiency has also been performed [10] .
Neurological dysfunction in children with
biotinidase deficiency manifests in the first few years
of life and typically presents with seizures, ataxia that
is associated with, skin rash and alopecia [11] . Children
with delayed clinical onset have optic atrophy, spastic
paraparesis and electromyographic evidence of
neuropathy as their presenting feature [11] . Our patient
had onset at 28 months. He had features seen in children
with early onset biotinidase deficiency but they were
mild including episodic ataxia, mild alopecia and
minimal skin lesion. Unlike many of those with early
onset, he had normal brain CT and MRI. Furthermore,
he had evidence of myelopathy on MRI spinal cord, a
finding rarely reported in children with onset after five
years [11] . Spinal cord involvement is rare in biotinidase
deficiency and is often difficult to recognize. In 1992,
Honavar et al [7,11] reported a patient with biotinidase
deficiency and a progressive neurological disorder
who died just before the biochemical diagnosis was
established. Postmortem examination of the brain, and
spinal cord revealed necrotizing lesions similar to those
seen in Leigh’s disease and Wernicke encephalopathy.
In addition, there was severe focal edema in deep
cerebral grey matter, brainstem and spinal cord [7,11] .
In our patient, MRI T2 weighted sequence revealed
an extensive hyper-intense lesion involving the
cervical spinal cord down to the dorsal segment with
inflammatory myelitis as a possibility; this suggest that
the differential diagnosis of unexplained spinal cord
demyelination should include biotinidase deficiency.
Dermatological lesions are a major feature of
biotinidase deficiency [7] . Our patient had mild perioral
lesions and mild alopecia. These could be mistaken for
nutritional problems. However, after treatment with
biotin dramatic improvement was observed.
Several studies have described patients with spinal
cord involvement in biotinidase difficiency. Table 1
compares such patients with our patient [7,12,13] .
Treatment with oral biotin (5 - 20 mg/day) is
both cheap and rewarding especially if started
early. The clinical symptoms, neurological and
neurophysiological findings as well as biochemical
findings will normalize after biotin therapy, whereas
delay in treatment leads to severe intellectual,
neurological, visual and hearing impairment.
CONCLUSION
In our culture, with high rates of consanguineous
marriages, one should always suspect inherited
metabolic disease. Biotinidase deficiency is one of them.
The disease is variable in its clinical, laboratory, and