Autism Spectrum Disorder as First Symptom of Neuronal Ceroid Lipofuscinosis Type 7 (NCL7)

Background: The neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of autosomal recessive lysosomal storage diseases which belong to the most frequent neurodegenerative disorders in childhood and adolescence. They are characterized by similar clinical symptoms like dementia, loss of vision and epilepsy as well as the retention of the wax-like ceroid lipofuscin material in brain, retina and other tissues. To date 14 distinct NCL-types are known which are classified by genetical aspects. All NCL-disorders show progressive deterioration and premature death. NCL7, also known as “Turkish” variant, usually appears in early childhood and is caused by mutations of the CLN7/MFSD8 gene.

Patient: A 3 years and 2 months old male patient with autism spectrum disorder and lacking speech development was referred to our institution for further diagnostic workup. Within a short time, he developed progressive ataxia with inability to walk and lost expressive language. The initial laboratory testing including chromosome analysis and basic metabolic investigations as well as EEG and MRI of the brain were normal. In the further course EEG changes appeared which finally resulted in an electrical status epilepticus during slow sleep (ESES) without clinical correlate. High-dose intravenous steroid treatment did not have any effect on this EEG pattern.

Results: We saw a patient with rapidly progressive deterioration of his cognitive and motor functions. MRI of the spine and brain, laboratory investigations of blood and CSF, nerve conduction velocity measurements as well as ENT and eye examinations were normal. By molecular genetic analysis, we could finally identify a homozygous mutation of the CLN7/MFSD8 gene and thus establish the diagnosis of NCL7. This “Turkish” variant has previously been described in the region of the Turkish city of Trabzon where the consanguine parents of our patient were born. The two older, healthy daughters of the parents were identified as heterozygous genetic carriers of the same variant. NCL-associated epilepsy appeared one year after the first presentation of our patient.

Discussion: Despite the heterogeneous phenotypes of the various NCL-subtypes, NCL7 usually presents with seizures. However, in our case the autistic behavior was the presenting symptom while motor and language regression as well as epilepsy only occurred in the later course of the disease. Therefore, NCL7 cannot be ruled out even if EEG, ophthalmologic examination and MRI of the brain are normal. NCL can present with autism spectrum disorder as first clinical finding and should be considered in the differential diagnosis of a child with regular early childhood development and developmental regression in late infancy until early school age.

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