Abstract
Introduction Neuronal ceroid lipofuscinosis-type 1 (NCL-1) is a neurodegenerative lysosomal storage
disorder. Vitamin D-dependent rickets type 1 (VDDR-1) is a rare cause of refractory
rickets. Here, we report an unusual association of NCL-1 with VDDR-1.
Case A 3-year-old boy presented with a history of seizures from 45 days of life, delayed
development, and loss of attained milestones at 20 months of age, along with progressive
vision impairment since 1 year. Examination showed a failure to thrive, microcephaly,
rachitic rosary, checkerboard and phylloid type of pigmentary mosaicism, fundus showed
disc pallor with generalized narrowing of arterioles, bilateral retinitis pigmentosa,
spasticity and dystonia, brisk reflexes, extensor plantar, and left choreoathetoid
movements. Investigations showed hypocalcemia (7.8 mg/dL), normal phosphorus (3.9 mg/dL),
elevated alkaline phosphatase (508.8 U/L), elevated parathyroid hormone (513.35 pg/mL),
low 1,25-dihydroxy-vitamin D (9.93 pg/mL), and normal renal function. The child had
metabolic acidosis, elevated ammonia (403.9 micromol/L), lactate (95 mg/dL, normal
range 4.5–19.8 mg/dL), and creatine phosphokinase (432 U/L) level, and normal tandem
mass spectroscopy. X-ray wrist showed healing vitamin deficiency rickets. Abnormal
electroencephalogram was suggestive of low voltage activity. Magnetic resonance imaging
brain showed gross cerebral and cerebellar atrophy. A muscle biopsy showed scattered
atrophic fibers and several ultrastructural granular osmiophilic deposits and some
mitochondrial aggregates of varying size were observed. Mitochondrial respiratory
chain enzyme assay exhibited complex-1 deficiency (activity < 30%). Genetic analysis
showed two pathogenic mutations: homozygous nonsynonymous variation c.674T > C in
exon 7 of the PPT1 gene and a homozygous frameshift variation c.1178_1179delAA in exon 7 of CYP27B1
confirming the diagnosis of NCL-1 with VDDR-1. The child was treated with a low protein
diet, levetiracetam, clonazepam, trihexyphenidyl, haloperidol, calcium supplement,
calcitriol, and sodium benzoate; some improvement in clinical and biochemical parameters
was noted on follow-up.
Conclusion This is a novel association of NCL-1 with VDDR-1 associated with complex-1 mitochondrial
deficiency which has previously not been reported in the literature.
Keywords NCL-1 - VDDR-1 - complex-1 deficiency - pigmentary mosaicism
