Case Report
Importance of Early Dental Care in a Child with Niemann-Pick Disease, Type C
Amparo Pérez1*, Clara Serna1, Antonio José Ortiz1 and Marcelo Bonecker2
1Department of Dentistry, Hospital Morales Meseguer, Spain
2Department of Pediatric Dentistry, Universidad de Sao Paulo, Spain
*Corresponding author: Amparo Pérez, Department of Integrated Pediatric Dentistry, Hospital Morales Meseguer, 2ª Planta, Avd Marqués de los Vélez sn, 30006, Murcia, Spain
Published: 25 Jan, 2018
Cite this article as: Pérez A, Serna C, Ortiz AJ, Bonecker
M. Importance of Early Dental Care in a
Child with Niemann-Pick Disease, Type
C. Ann Clin Case Rep. 2018; 3: 1493.
Abstract
Niemann Pick disease is an autosomal recessive neurodegenerative disorder produced by an accumulation of intracellular cholesterol in lysosomes and endosomes. It manifests in middleto- late childhood and provokes ataxia, dysarthria, dysphagia (making oral nutrition difficult), hypotonia, spasticity, seizures and developmental abnormalities, which means that maintaining oral hygiene is difficult. A six-year-old girl diagnosed with Niemann Pick type C, currently treated with 2-hydroxypropyl-beta-cyclodextrin-intrathecal. Her oral health has been managed for 4 years applying the caries management by risk assessment (CAMBRA) preventive protocol. Through oral hygiene maintenance at home (good brushing technique, and 0.12% chlorhexidine mouthwash) and three-monthly plaque check-ups and fluoride varnish applications, the child has remained free of caries. From the outset, treatment has included psychological management with the help of the patient’s mother. The use of preventative protocols makes it possible to manage the oral health of children with Niemann Pick disease. The help and participation of the family are essential to the oral health and psychological management of children with this disease.
Abbreviations
CAMBRA: Caries Management by Risk Assessment; NPC: Niemann-Pick Disease Type C; HPBCD: Hydroxypropyl-Beta-Cyclodextrin; ICDAS: The International Caries Detection & Assessment System; DMEM: Dulbecco's Modified Eagle's Medium
Introduction
Niemann-Pick disease type C (NPC) is an autosomal recessive neurodegenerative disorder caused by the mutation of two genes. In 95% of families, it is caused by mutations in the NPC1 gene, whose cytogenetic location is 18q11.2, NPC type 1 (257220). In the remaining 5% of families, it is produced by mutations in the gene NCP2, with cytogenetic location 14q24.3, NPC type 2 (607625). Its minimum incidence is estimated to be 1:150,000 of newborn live babies in Western Europe, and usually manifests in middle-to-late childhood. The clinical manifestations are similar in both types of NPC, as they are produced by intracellular transportation of endocytosed cholesterol with sequestration of unesterified cholesterol in lysosomes and late endosomes. This provokes an accumulation of cholesterol and sphingolipids in particular organs. Niemann Pick Type D is a specific form of NPC 1 in patients of Nova Scotia Acadian ancestry. Niemann-Pick disease type A and B are different and provoked by deficits in sphingomyelinase activity [1]. The accumulation of lipids in the liver can provoke severe hepatic disease with hepatosplenomegaly and cirrhosis. If they accumulate in the lungs they can cause respiratory failure. The accumulation of glycosphingolipids is typical in cases with neurological disorders such as ataxia, dysarthria, dysphagia (making oral nutrition difficult), hypotonia, spasticity, seizures and developmental abnormalities that can lead to dementia. Death occurs in the late second or third decade of life but may occur sooner [2,3]. Caries is a multifactorial disease and its development is determined by the teeth themselves, the bacterial ecosystem, diet and oral hygiene habits. Any change in these factors can affect individual susceptibility, risk, and caries activity [4]. As in the case of special patients, prompt dental care of patients with rare diseases will help them to enjoy a better quality of life. This will allow early diagnosis of oral diseases, and the use of preventative protocols can avoid the appearance of pathologies and facilitate and simplify the clinical management of these patients.
Figure 1
Figure 1
Front and lateral radiographs of the head were it can see the
Ommaya reservoir. The intrathecal treatment with hydoxypropyl-betacyclodextrin
(HPBCD) is placed.
Figure 2
Figure 2
Protrusion in upper jaw and gingivitis in lower jaw. The child has
frequent tartar formation on the second molars.
Figure 3
Figure 3
As soon as the deciduous teeth, 7.1 and 8.1, were extracted, they
were submerged in Dulbecco's Modified Eagle's medium (DMEM) for later
investigation of Niemann-Pick type C disease.
Case Presentation
Medical history
A Caucasian girl of 6 years of age was first referred to the University
of Murcia Dental Clinic 4 years ago. Without family antecedents, she
was diagnosed with Niemann Pick disease type C at the age of two at
the Virgen de la Arrixaca University Hospital (Murcia, Spain).
She presented encephalopathy, seizures controlled by medication,
psychomotor retardation, dysphagia, and spastic tetraparesis. The girl
received enteral nutrition via a gastronomy tube.
Since diagnosis the patient had been medicated with miglustat
(glucosylceramide synthase inhibitor). Due to the poor neurological
evolution of the disease, authorization was requested from the
Spanish Ministry of Health to begin compassionate treatment with
intrathecal hydroxypropyl-beta-cyclodextrin (HPBCD). She has been
treated with this experimental drug since April 13th 2012, which she
receives 400 mg every 15 days, in an Ommaya reservoir (Figure 1)
with local analgesia without sedation; the patient has suffered no
incident or complications arising from sedation, or secondary effects
or allergy to the medication. During the last few months, the child has
begun to take small amounts of puréed food, although not every day.
Dental history
Clinical examination found that the child presented dental
development compatible with her age, acute gingivitis (Figure 2),
hyposalivation with thick saliva, and frequent tartar formation on
the second molars. The International Caries Detection & Assessment
System (ICDAS) was used to diagnose caries, finding that she did not
present caries. The CAMBRA method was also used to evaluate the
risk of caries and to elaborate a treatment plan.
Discussion
For children with systemic disease that make oral hygiene
maintenance difficult it is important to manage dental health care
from an early age, using preventative dental protocols to avoid
future restorative treatment and to provide a better quality of life.
These systemically compromised patients attend frequent hospital
appointments in which they undergo numerous clinical tests, a
situation which compromises their behavior when it comes to dental
health care. At the first appointment, it was decided not to use any type
of drug-based management but to use psychological management as
a technique for managing her behavior. Although the child suffered
neurological deterioration and could not speak, her understanding
was sufficient to permit this approach. The presence and help of her
mother was fundamental to attending to the patient, as she was able
to assist communication with the patient.
The patient remained in her wheelchair, which avoided any
need for her to get used to a new ‘environment’ that might affect
her behavior. The behavior management techniques used included
a combination of desensitization, ‘tell-show-do,’ non-verbal
communication, and voice control. The fact that the child did not
need invasive treatment facilitated management, although there were
moments when she broke down in tears.
According to the CAMBRA protocol, the child is considered a
high-risk patient [4]. For the last 4 years, since she was first referred
to the clinic, she has received preventative dental treatment every
three months. She and her parents have been instructed in oral health
care, correct tooth brushing techniques and 0.12% chlorhexidine
application to manage gingivitis [5]. Manual prophylaxis is performed
manually with curettes and fluoride varnish is applied every 3 months.
Caries management is carried out by visual examination, as no bite plate radiograph has been taken due to the family’s unwillingness
for their daughter to undergo any more X-rays as she has undergone
numerous general X-rays over the years.
Four years on, the girl has remained free of caries, although
gingivitis management has produced less positive outcomes due to
the fact that the patients is not fed by mouth and presents a low saliva
production, accompanied by a Angle Class II malocclusion.
As the patient presents dysphagia, to prevent possible aspiration
deciduous teeth were extracted as soon as the parents noticed
slight mobility of a tooth. A chronological disorder has occurred
in exfoliation; the first tooth lost was 6.1, followed by 5.1. The last
teeth to be extracted were 7.1 and 8.1 (Figure 3). As soon as they had
been extracted they were submerged in Dulbecco's Modified Eagle's
Medium (DMEM) for later investigation of Niemann-Pick type C
stem cells. On the same day, the normal eruption of 1.1 and 2.1 was
observed. Extractions were performed infiltrating 2% Lidocaine and
epinephrine 1:100.000, after topical anaesthesia with Hurricaine®.
The extractions were performed without difficulty as the child was
attending the clinic every three months and was always seen by the
same dentist, which has helped her to get used to the clinic and staff.
Although the child does not speak, she recognizes the dentist, and her
facial expressions and reactions are interpreted by the mother.
Conclusion
1. Child patients with rare diseases that cause physical impairments
must attend the pediatric dental clinic as young as possible to receive
three-monthly program of preventative measures, as these patients
are at high risk from caries.
2. Oral preventative protocols are of fundamental importance to
the avoidance of more complicated restorative treatment; they will
also help patients to have a better quality of life. The participation and
help of parents in oral hygiene maintenance is essential and parents
should be instructed to this end.
3. In children with Niemann Pick type C disease, extraction
of deciduous teeth should be performed as soon as the mobility of
each tooth is noticed in order to avoid possible aspiration due to the
dysphagia that these patients present.
Declarations
Ethics approval and consent to participate
The Research Ethics Committee of the University of Murcia
considers that this case report is exempt from ethical approval (Ref:
1361/2016).
The girl’s mother signed the informed consent of the Dental
Clinic of the University of Murcia before starting the implementation
of the CAMBRA protocol.
Acknowledgement
We are grateful to child’s family for trusting us. She died January, 3, 2017 with 7 years old.
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