A Rare Case of Neuronal Ceroid Lipofuscinosis-Type 1 (NCL-1) with Vitamin D-Dependent Rickets-Type 1 (VDDR-1), Complex 1 Mitochondrial Deficiency, and Mixed Variant—Checkerboard and Phylloid Type of Pigmentary Mosaicism

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.