Infantile neuroaxonal dystrophy associated with α-N-acetylgalactosaminidase deficiency: on relating axonal spheroids to a lysosomal enzyme deficiency

1995 ◽  
pp. 197-207
Author(s):  
D. Wolfe
Keyword(s):  
Lysosomal Enzyme ◽  
Enzyme Deficiency ◽  
Neuroaxonal Dystrophy ◽  
Infantile Neuroaxonal Dystrophy ◽  
Axonal Spheroids

scholarly journals Fetal neuroaxonal dystrophy: a new etiology of fetal akinesia

2018 ◽  
Vol 45 (S1) ◽  
pp. S3-S4
Author(s):  
C. Fallet-Bianco ◽  
B. Hargitai ◽  
P. Bonasoni ◽  
F. Guimiot ◽  
M.T. Yacoubi
Keyword(s):  
Pregnancy Termination ◽  
Age Groups ◽  
Molecular Study ◽  
Neuroaxonal Dystrophy ◽  
Infantile Neuroaxonal Dystrophy ◽  
Term Neonates ◽  
Axonal Spheroids ◽  
Phenotypic Spectrum ◽  
Associated Malformations ◽  
Cns Malformations

Neuroaxonal Dystrophies (NAD) are neurodegenerative diseases characterized by axonal “spheroids” occurring in different age groups. The identification of mutations delineated new molecular entities in these disorders. We report neuropathological data of a new form of NAD, characterized by a precocious prenatal onset, different from classical and connatal Infantile Neuroaxonal Dystrophy (INAD).We studied 5 fetuses examined after pregnancy termination and 2 term neonates deceased just after birth, 4/7 from consanguineous parents. All subjects presented severe fetal akinesia sequence with microcephaly. In 4/7 cases, a molecular study was performed. In all cases, “spheroids” with typical immunohistochemical features were identified, with variable spreading in the central and peripheral nervous system. Basal ganglia, brainstem, cerebellum and spinal cord involvement was constant. Associated CNS malformations, unusual in INAD, were associated including hydrocephalus (2), callosal agenesis/hypoplasia (2), olfactory agenesis (1), cortical (3) and retinal (1) anomalies. None cases demonstrated mutations in PLA2G6, found in INAD.The clinical and neuropathological features of these fetal cases are different from those of “classical” INAD. The absence of mutations of PLA2G6, in addition, suggests that the fetal NAD is a new entity, distinct from INAD, with different molecular basis. Associated malformations suggest a wide phenotypic spectrum and probable genetic heterogeneity. Finally, fetal NAD is an additional etiology of fetal akinesia.

scholarly journals 'Hallervorden-Spatz syndrome - infantile neuroaxonal dystrophy' complex: case report

1988 ◽  
Vol 46 (1) ◽  
pp. 69-72 ◽  
Author(s):  
A. U. Bresolin ◽  
L. Pascuzzi ◽  
R. Melaragno Filho ◽  
Maria H. Fontana ◽  
R. Pécora ◽  
...  
Keyword(s):  
Case Report ◽  
Cerebral Atrophy ◽  
Neuroaxonal Dystrophy ◽  
Complex Case ◽  
Pathological Examination ◽  
Infantile Neuroaxonal Dystrophy ◽  
Axonal Spheroids ◽  
Mental Deterioration ◽  
One Year ◽  
Red Coloration

Case report of a 7 1/2-years old girl considered as being normal until the age of 2 years. From then on she progressed with gait disturbance, mental deterioration, dystonic movements, convulsions and dysarthria. She died of bronchopneumonia one year later. CT scan showed hyperdensity at the putamina, with no signs of cerebral atrophy. Pathological examination disclosed an intense red coloration of the putamina and axonal «spheroids» at electron microscopy.

scholarly journals Fetal neuroaxonal dystrophy: a further etiology of fetal akinesia

2021 ◽  
Vol 48 (s1) ◽  
pp. S4-S4
Author(s):  
C Fallet-Bianco ◽  
B Hargitai ◽  
P Bonasoni ◽  
F Guimiot ◽  
MT Yacoubi
Keyword(s):  
Pregnancy Termination ◽  
Age Groups ◽  
Molecular Study ◽  
Neuroaxonal Dystrophy ◽  
List Type ◽  
Fetal Life ◽  
Infantile Neuroaxonal Dystrophy ◽  
Axonal Spheroids ◽  
Phenotypic Spectrum ◽  
Associated Malformations

Neuroaxonal Dystrophies (NAD) are neurodegenerative diseases characterized by axonal “spheroids” occurring in different age groups. The identification of mutations delineated new molecular entities in these disorders. We report neuropathological data of a new form of NAD, characterized by a precocious prenatal onset, different from classical and conatal Infantile Neuroaxonal Dystrophy (INAD).We studied 5 fetuses examined after pregnancy termination and 2 term neonates deceased just after birth, 4/7 born from consanguineous parents. All subjects presented severe fetal akinesia sequence with microcephaly. In 4/7 cases, a molecular study was performed. In all cases, “spheroids” with typical immunohistochemical features were identified, with variable spreading in the central and peripheral nervous system. Basal ganglia, brainstem, cerebellum, and spinal cord involvement was constant. Associated CNS malformations, unusual in INAD, were associated including hydrocephalus (2), callosal agenesis/hypoplasia (2), olfactory agenesis (1), cortical (3) and retinal (1) anomalies. None of the cases demonstrated mutations in PLA2G6, found in INAD. The clinical and neuropathological features of these fetal cases are different from those of “classical” INAD. The absence of mutations in PLA2G6, in addition, suggests that the fetal NAD is a new entity, distinct from INAD, with different molecular basis. Associated malformations suggest a wide phenotypic spectrum and probable genetic heterogeneity. Finally, fetal NAD is an additional etiology of fetal akinesia.LEARNING OBJECTIVESThis presentation will enable the learner to:Diagnose this rare form of neuroaxonal dystrophy (NAD) occurring precociously, in the fetal life, as soon as the second trimester, different from the infantile form of NAD. 1.Describe the phenotypic spectrum of this fetal NAD; fetal akinesia sequence, microcephaly and various brain malformations, different from the “classical” and conatal forms of infantile neuroaxonal dystrophy.2.Consider this etiology in the diagnosis of fetal akinesia sequence.

scholarly journals The Natural History of Infantile Neuroaxonal Dystrophy

2020 ◽  
Author(s):  
Fadie D Altuame ◽  
Gretchen Foskett ◽  
Paldeep Atwal ◽  
Sarah Endemann ◽  
Mark Midei ◽  
...  
Keyword(s):  
Natural History ◽  
Neurodegenerative Disorder ◽  
Gastrointestinal Disease ◽  
Cerebellar Atrophy ◽  
Neuroaxonal Dystrophy ◽  
Fine Motor ◽  
Speech Impairment ◽  
Infantile Neuroaxonal Dystrophy ◽  
Significant Difference ◽  
History Of

Abstract Background: Infantile neuroaxonal dystrophy (INAD) is a rapidly progressive neurodegenerative disorder of early onset causing premature death. It results from biallelic pathogenic variants in PLA2G6, which encodes a calcium‐independent phospholipase A2. Objective: We aim to outline the natural history of INAD and provide a comprehensive description of its clinical, radiological, laboratory, and molecular findings. Materials and Methods: We comprehensively analyzed the charts of 28 patients: 16 patients from Riyadh, Saudi Arabia, 8 patients from North and South America and 4 patients from Europe with a molecularly confirmed diagnosis of PLA2G6‐associated neurodegeneration (PLAN) and a clinical history consistent with INAD.Results: In our cohort, speech impairment and loss of gross motor milestones were the earliest signs of the disease. As the disease progressed, loss of fine motor milestones and bulbar dysfunction were observed. Temporo-frontal function was among the last of the milestones to be lost. Appendicular spastic hypertonia, axial hypotonia, and hyperreflexia were common neurological findings. Other common clinical findings include nystagmus (60.7%), seizures (42.9%), gastrointestinal disease (42.9%), skeletal deformities (35.7%), and strabismus (28.6%). Cerebellar atrophy and elevations in serum AST and LDH levels were consistent features of INAD. There was a statistically significant difference when comparing patients with non-sense/truncating variants compared with missense/in-frame deletions in the time of initial concern (p = 0.04), initial loss of language (p = 0.001), initial loss of fine motor skills (p = 0.009), and initial loss of bulbar skills (p = 0.007).Conclusion: INAD is an ultra-rare neurodegenerative disorder that presents in early childhood, with a relentlessly progressive clinical course. Knowledge of the natural history of INAD may serve as a resource for healthcare providers to develop a targeted care plan and may facilitate the design of clinical trials to treat this disease.

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