Familial Kufs' disease presenting as a progressive myoclonic epilepsy

Abstract

Kufs' disease is the adult form of a group of disorders referred to as neuronal ceroid-lipofuscinosis or Batten's disease. We report here the clinical and anatomopathological features of two young brothers presenting with a progressive myoclonic epilepsy corresponding to type A of the disease according to Berkovic. The first clinical manifestations occurred before 20 years of age. Diagnosis was made in the older brother at autopsy and in the younger brother from a rectal biopsy. In addition to characteristic electron microscopic findings, enlarged neurons showed strong immunoreactivity against subunit c of mitochondrial ATP synthase which has been reported previously in only a few adult cases of neuronal ceroid-lipofuscinosis. An extensive review of the published cases underlines the rarity of this condition, particularly when onset is early.

Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease)

“…In general, misdiagnosis occurred by overinterpretation of ultrastructural findings in biopsy samples, with failure to distinguish normal lipofuscin that accumulates with age, from abnormal lipopigment seen in NCL, which may be very limited in ANCL. [6][7][8][9][10][11][12][13] In children, this distinction is easier, contrasting abundant storage in disease with minimal normal age-related pigment. Rather than relying on the amount of lipopigment, accurate diagnosis depends on analysis of the particular ultrastructural features.…”

“…Kufs type A presents with progressive myoclonus epilepsy, whereas Kufs type B presents with dementia and motor signs. 6,13 Recessive mutations in CLN6 [14][15][16] and dominant mutations in DNAJC5 [17][18][19] can cause Kufs type A; Kufs type B can be caused by recessive mutations in CTSF. 20,21 Rare cases of ANCL with retinal involvement are described due to mutations in PPT1 (CLN1), 22,23 CLN5, 24,25 and GRN.…”

“…Stored material is usually only found in a subset of neurons, with the accumulation of age-related lipofuscin often confused with pathologic storage. [6][7][8][9][10][11][12][13] Furthermore, molecular genetic characterization of ANCL is at an early stage. Hindered by the small number of cases, and the clinical and pathologic challenges, ANCL is poorly understood.…”

“…These criteria were based on review of the literature and the clinical experience of Consortium members. [6][7][8][9][10][11][12][13] Clinical and pathologic review of cases. Strenuous attempts were made to source detailed clinical data from treating clinicians.…”

Neuronal ceroid-lipofuscinoses

“…Kufs disease type A (CLN4A) is inherited in an autosomal recessive manner and presents with progressive myoclonus. Kufs disease type B (CLN4B), which presents with dementia and various motor-system signs, is the only NCL with presumed autosomal dominant inheritance pattern [90][91][92][93][94]. Ultrastructural examination may show GRODs or FPPs.…”