J Pediatr Genet 2024; 13(04): 291-299
DOI: 10.1055/s-0044-1787196
Original Article

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

1   Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India
,
Anusha Raj K.
1   Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India
,
Varunvenkat M. Srinivasan
1   Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India
,
Dhananjaya K. Vamyanmane
2   Department of Pediatric Radiology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India
,
Sahana M. Srinivas
3   Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India
,
Yasha Chickabasaviah
4   Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
,
Rashmi Santhoshkumar
5   Electron Microscope Laboratory, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
,
Pallavi Mittal
6   Department of Molecular Biology, Bione Ventures Private Limited, Bangalore, Karnataka, India
,
Surendra K. Chikara
6   Department of Molecular Biology, Bione Ventures Private Limited, Bangalore, Karnataka, India
,
Gurudatta Baraka Vishwanathan
7   Centre for Human Genetics, Bengaluru, Karnataka, India
› Institutsangaben

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.

Authors' Contributions

V.K. and V.V. were involved in the supervision, guidance, and review of the manuscript. A.K., D.V., S.S., Y.C., R.S., P.M., S.C., G.D. were involved in the diagnosis of the child and the preparation of the manuscript.




Publikationsverlauf

Eingereicht: 02. März 2023

Angenommen: 26. April 2024

Artikel online veröffentlicht:
30. Mai 2024

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