[MIM 204 200, 204 500, 256 730, 600 143, 609 055, 610 127]

(Ceroid-lipofuscinoses)

Group of Lysosomal Storage Disease. Generally autosomal recessive transmission. Prevalence: 1/12500. Intralysosomal accumulation of lipofuscin and ceroid . Nine varieties (13 genes) have been described: all combine progressive dementia, loss of vision, seizures and motor problems. They were conventionally classified according to their time of onset and the order of appearance of the symptoms. Their genetic and allelic heterogeneity required the development of a new classification (table) which takes into account the responsible gene and the age at the onset of the symptoms.

Three deficient enzymes have been identified so far:

-        palmitoyl-protein thioesterase (PPT-1 gene on 1p32)

-        tripeptidyl-peptidase (TPP-1 gene on 11p15)

-        cathepsin (CTSD gene on 11p15.5)

The best-known are:

• infantile form (Santavuori-Haltia disease, CLN1) [MIM 256 730] (TPP-1 gene on 1p32): regression of the acquired skills  around the age of 12 months ; later, indifference to the family circle, myoclonic jerks, loss of vision. Rapidly evoluting cerebral atrophy progressing to an isoelectic EEG around the age of 4 years;  a vegetative state follows and death occurs around the  age of 8-12 years;
• late 'classic' infantile form (Jansky-Bielschowsky disease, CLN2, TPP-1 gene on 11p15) [MIM 204 500]; onset between 2 and 4 years of age with convulsions, loss of the acquired skills and myoclonic ataxia; loss of vision appears around 4 to 6 years; life expectancy: 6 years from the beginning of adolescence
• classical juvenile form (CLN3 gene on 16p11.2, Spielmeyer-Vogt or Batten disease) [MIM 204 200]: most common form; onset between 4 and 10 years of age with progressive decrease in visual acuity (pigmentary degeneration of the retina); then  intellectual deterioration and behavior disorders; dysarthria, seizures; later, cardiac problems: ventricular hypertrophy, conduction or rhythm disorders. Episodes of paroxysmal sympathetic hyperactivity in adolescence. Risk of drug-induced fever with rhabdomyolysis similar to a neuroleptic malignant or serotonin syndrome.
• variants of the late infantile form:

-        Haltia-Santavuori type [Hagberg-Santavuori-Haltia] (chromosome 13q31.32): onset between 4 and 7 years of age; epilepsy, polymyoclonia, ataxia, dementia

-        late infantile Finnish type  [MIM 256 731, 601 780], CLN5: onset between 4.5 and 7 years of age

-        late infantile form CLN 6: loss of vision and seizures are the initial symptoms

-        CLN7: vision loss and seizures are the initial symptoms

-        CLN8: earlier: onset between 2 and 6 years of age

• adult forms: Kufs disease type A (CLN6) or B (CTSF); Parry disease [MIM 162 350]: onset between 11 and 50 years of age.

Experimental treatment: selenium-rich diet; studies of phase 1 of  intracerebral and intraventricular transplantation of cerebral stem cells in children with infantile or late-infantile forms. For the CLN2 form: intracerebroventricular injections (through an Ommaya's reservoir) of cerliponase-alpha to slow the evolution. Risk of fever, vomiting or anaphylactic reaction.

Anesthetic implications:

epilepsy, behavioral disorders. If case of CLN3 mutation: preoperative cardiac evaluation, early in adolescence: disorders of intracardiac conduction, ventricular hypertrophy ? Increased risk of drug-induced fever with rhabdomyolysis similar to neuroleptic malignant syndrome or serotonin syndrome in classic juvenile (CLN3).

Treatment of epilepsy: carbamazepine, phenytoin and lamotrigine may aggravate epilepsy; valproic acid can cause excessive sedation.

For the infantile form, risk of hypothermia and sinus bradycardia under anaesthesia, especially as soon as clinical signs of the disease are present.

References : 

• Defalque JR.
  Anesthesia for a patient for Kufs’ disease.
  Anesthesiology 1990 ; 73: 1041-2.
• Gopalakrishnan S, Sidduiqui S, Mayhew JF.
  Anesthesia in a child with Batten disease.
  Pediatr Anesth 2004 ; 14 :890-1.
• Pereira D, Pereira M, Caldas F. 
  Anesthesia management in neuronal ceroid lipofuscinoses. 
  Pediatr Anesth 2006 ; 16 : 356-7.
• Miao N, Levin SW, Baker EH, Caruso RC, Zhang Z, Gropman A, Koziol D, Wesley R, Mukherjee AB, Quezado ZMN. 
  Children with infantile neuronal ceroid lipofuscinosis have an increased risk of hypothermia and bradycardia during anesthesia. 
  Anesth Analg 2009; 109: 372-8.-
• Yamada Y, Doi K, Sakura S, Saito Y. 
  Anesthetic management for a patient with Jansky-Bielchowsky disease. 
  Can J Anesth 2002; 49: 81-3.
• Adams HR, Mink JW, Univ Rochester Batten Center Study Group.
  Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease). 
  J Child Neurol 2013 ; 28 : 1128-36. 
• Mole SE, Williams RU, Wisniewski KE. 
  Neuronal ceroid-lipofuscinoses. 
  In GeneReviews edited by Pagon RA, Adam MP, Bird TD et al, Seattle 2013
• Selden NR, Amira A-U, Huhn SL, Koch TK et al. 
  Central nervous system stem cell transplantation for children with neuronal ceroid liposfuscinosis. 
  J Neurosurgery-Pediatrics 2013; 11: 643-52 
• Kako H, Martin DP, Tobias JD.
  Perioperative care of a patient with neuronal ceroid lipofuscinosis.
  Saudi J Anesth  2013 ; 7: 336-40.
• Richa F. 
  Anaesthesia and orphan disease : a child with neuronal ceroid lipofuscinosis. 
  Eur J Anaesthesiol 2015; 32: 213-5. 
• Fujumura S, Saito Y, Saito T, Komaki H et al.
  Progressive conduction defects and cardiac death in late infantile neuronal ceroid lipofuscinosis.
  Develop Med Child Neurol 2012 ;54 :663-6.
• Wang S, Pei L.
  Anaesthesia and orphan disease : a 2-year-old old with ceroid lipofuscinosis.
  Eur J Anaesthesiol 2020; 37: 138-41.
• Yamaguchi Y, Lyman R, De Los Reyes E, Kim SS, Uffman JC, Tobias JD.
  Batten disease and perioperative complications : a retrospective descriptive study.
  J Anesth 2020; 34:342-7
• Savvidou A, Jennions E, Wikström S, Olsson-Engman M, Sofou K, Darin N.
  Drug-induced hyperthermia with rhabdomyolysis in CLN3 disease.
  Eur J Paed Neurol 2022 ; 39 : 74-8

Updated: October 2022