Diagnosis Of Infantile Neuroaxonal Dystrophy Research Articles

Siblings with Infantile Neuroaxonal Dystrophy

AbstractA 2 years 3 months male toddler with motor delay and his female sibling with history of marked global developmental regression following an intercurrent febrile illness were both noted to have phospholipase A2G6 (PLA2G6) mutation, confirming the diagnosis of infantile neuroaxonal dystrophy (INAD). This case report attempts to familiarize readers with the pleomorphic presentation of INAD and the role of early clinical identification, examination, and prompt genetic testing in establishing a diagnosis.

The clinical characteristics and molecular genetics of infantile neuroaxonal dystrophy: The current research progress

Infantile neuroaxonal dystrophy (INAD) is a rare autosome-recessive disease characterized by progressive motor and cognitive regression. The PLA2G6 gene is its causative gene, which encodes calcium-independent phospholipase A2 enzyme (iPLA2-VIA). The diagnosis of INAD is difficult because of its clinical heterogeneity, and the rate of misdiagnosis is high. The purpose of this study is to describe the clinical characteristics, molecular genetics, treatment and prognosis of INAD to improve the acknowledgement of INAD in medical workers and to help make an early diagnosis of INAD. Key words: Neuroaxonal dystrophies/DI/TH/GE; Infant; Editorial

Cerebellar atrophy without cerebellar cortex hyperintensity in infantile neuroaxonal dystrophy (INAD) due to PLA2G6 mutation

Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disorder characterized by infantile onset and rapid progression of psychomotor regression and hypotonia evolving into spasticity. The neuroradiologic hallmark of the disease is represented by cerebellar atrophy and signal hyperintensity in the cerebellar cortex on MR T2-weighted images. We report a 2-year-old boy with psychomotor regression and hypotonia carrying a homozygous 5′ splice site mutation in PLA2G6 gene, whose brain MRI revealed cerebellar atrophy with normal cerebellar cortex signal intensity. The absence of the signal hyperintensity of the cerebellar cortex does not rule out the diagnosis of INAD.

Infantile neuroaxonal dystrophy: Axonal changes in biopsied muscle tissue

Dystrophic axons were found in the biopsied muscle tissue of a 17-month-old hypotonic infant after confirmation of a diagnosis of infantile neuroaxonal dystrophy (INAD) by subsequent peripheral nerve biopsy. He manifested gradual deterioration and had brief tonic seizures. The sural nerve biopsy, performed at age 42 months, confirmed INAD. Intensive ultrastructural investigation of the preceding muscle biopsy specimens demonstrated infrequent but definite findings of axonal degeneration in the musculature. Ultrastructural investigation of muscle biopsy should include a careful search for neural tissue because in INAD axonal changes occur primarily in the presynaptic region.

The use of magnetic resonance imaging in diagnosing infantile neuroaxonal dystrophy

We used MRI to investigate the brains of four children ranging from 3 to 10 years of age with infantile neuroaxonal dystrophy. T2-weighted imaging revealed characteristic findings of marked cerebellar atrophy and diffuse hyperintensity of the cerebellar cortex. At autopsy, one child had extensive astrogliosis and neuronal loss with shrinkage of the cerebellar cortex, in addition to typical widespread changes of neuroaxonal dystrophy. The characteristic hyperintensity of the cerebellar cortex on T2-weighted imaging probably is secondary to the extensive gliosis and shrinkage of the cerebellar cortex. These cerebellar findings on MRI may permit early diagnosis of infantile neuroaxonal dystrophy.

MRIが診断に有用であったinfantile neuroaxonal dystrophyの1例

MRIが診断に有用であったinfantile neuroaxonal dystrophyの1例

Skin biopsy is useful for diagnosis of infantile neuroaxonal dystrophy

Skin biopsy is useful for diagnosis of infantile neuroaxonal dystrophy

New enzymatic findings in infantile neuroaxonal dystrophy.

Two siblings with infantile neuroaxonal dystrophy (INAD) exhibited highly increased activity of nonspecific esterase (resistant to physostigmine and sensitive to organophosphates) topically correlating with the morphological manifestations of the disease (spheroids), confined in those two particular cases to the central nervous system (CNS). This is demonstrated for the first time. NADH tetrazolium reductase was another enzyme noted with increased activity and similar topography. The lesions were devoid of any marked activity of typical mitochondrial (succinate and alpha-glycerolphosphate) dehydrogenases and lysosomal (acid phosphatase and beta-glucuronidase) enzymes. The diagnostic significance of monitoring non-specific esterase and NADH tetrazolium reductase activities in the diagnosis of INAD is discussed in particular.

Skin and conjunctival biopsies in infantile neuroaxonal dystrophy

The diagnosis of infantile neuro-axonal dystrophy (INAD) in a 5-year-old patient was confirmed by the ultrastructural study of neuromuscular, skin and conjunctival biopsy specimens. Abnormal networks of smooth membranous, lamellar and tubular profiles were found in presynaptic terminals and in conjunctival and dermal axons. INAD is the first neurological disease outside the group of storage disorders in which skin and conjunctival biopsies contribute significiantly to the diagnosis.

Infantile neuroaxonal dystrophy. Ultrastructural study of the peripheral nerves and of the motor end plates.

Ultrastructural studies of peripheral nerves and motor end-plates are performed in a case of neuroaxonal dystrophy already diagnosed on the basis of clinical and morphological data (brain biopsy). Lesions similar to those described in the central nervous system are found in the extra- and intrafusal axons and motor end plates. The sensory nerve shows only discrete alterations. Although it is widely recognized that many other diseases are characterized by the presence of axonal spheroids, the combination of the relevant clinical data and the positive results of a motor end-plate biopsy allow the diagnosis of infantile neuroaxonal dystrophy to be made, obviating or alleviating the need of a brain biopsy.