Type 2 Gaucher disease: 15 new cases and review of the literature.
OBJECTIVE
To provide a description of type 2 Gaucher disease. To attempt to define type 2 Gaucher disease within the spectrum of early-onset neuronopathic Gaucher disease.


BACKGROUND
Type 2 Gaucher disease is a rare disorder due to glucocerebrosidase deficiency that comprises a rapidly progressing neurological degeneration associated with visceral signs. Most data collected rely on the description of single cases or siblings. Cases of perinatal-lethal Gaucher disease are frequently considered as type 2 Gaucher patients, though the clinical presentation is different.


METHODS
We retrospectively studied the clinical history of 15 original acute Gaucher disease patients and reviewed the available data of 104 published cases of early-onset neuronopathic Gaucher disease, including 61 patients with the acute type and 43 cases of the perinatal-lethal form.


RESULTS
The neurological presentation of type 2 Gaucher disease is homogeneous and characterized by precocious, severe, and rapidly progressive brainstem degeneration in the foreground. The most frequent initial signs are hyperextension of the neck, swallowing impairment, and strabismus. Provoked asphyxic episodes generally appear in a second time. They are followed by prolonged spontaneous apneas that seem to be the main pejorative feature. Other neurological signs may be observed, but epilepsy, myoclonic epilepsy/myoclonus, trismus, stridor, and progressive microcephaly are less characteristic. Psychomotor regression may occur, but is not a typical feature of the disease onset. Chronic or subacute pulmonary disease predominates in the visceral involvement. Hepatosplenomegaly, failure to thrive, thrombocytopenia, and anemia are the other remarkable, albeit non-specific, features. The inflammatory component of Gaucher disease is underlined by the addition of unexplained fever to this systemic clinical picture. The natural history and particular signs of perinatal-lethal Gaucher disease do not belong to the type 2 Gaucher disease phenotype.


CONCLUSIONS
Type 2 Gaucher disease is a clinically homogeneous entity. The specificity of the neurological involvement is sufficient to suspect the diagnosis at the onset of the disease. Type 2 and perinatal-lethal Gaucher diseases are easily distinguishable in most cases.
Mignot
Cyril
C
Service de Neurologie Pédiatrique, Hôpital Armand Trousseau, AP-HP, Paris, Centre de Référence des Maladies Lysosomiales, 26 avenue du docteur Arnold Netter, 75012 Paris, France
Doummar
Diana
D
Maire
Irène
I
De Villemeur
Thierry Billette
TB
D000293:Adolescent; D017668:Age of Onset; D001933:Brain Stem / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005776:Gaucher Disease / Q000145:classification / Q000175:diagnosis / Q000503:physiopathology*; D005962:Glucosylceramidase / Q000172:deficiency; D006801:Humans; D008297:Male; D009410:Nerve Degeneration / Q000503:physiopathology; D012189:Retrospective Studies; D012196:Review Literature as Topic
D005962:Glucosylceramidase