Fever, and Babinski sign

This disease is characterised by progressive cerebellar ataxia with pyramidal and spinal cord dysfunction, associated with distinctive MRI anomalies and increased lactate in the abnormal white matter.

LEUKOENCEPHALOPATHY WITH BRAIN STEM AND SPINAL CORD INVOLVEMENT-HIGH LACTATE SYNDROME Is also known as mitochondrial aspartyl-trna synthetase deficiency|leukoencephalopathy with brain stem and spinal cord involvement-lactate elevation syndrome|lbsl

• Intellectual disability
• Seizures
• Generalized hypotonia
• Ataxia
• Nystagmus

SOURCES: MESH OMIM ORPHANET MENDELIAN

HYPERPHENYLALANINEMIA, BH4-DEFICIENT, B; HPABH4B Is also known as gtp cyclohydrolase i deficiency|hyperphenylalaninemia, tetrahydrobiopterin-deficient, due to gtp cyclohydrolase i deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Strabismus

SOURCES: OMIM MENDELIAN

Autosomal recessive dopa-responsive dystonia (DYT5b) is a very rare neurometabolic disorder characterized by a spectrum of symptoms ranging from those seen in dopa-responsive dystonia (DRD) to progressive infantile encephalopathy.

AUTOSOMAL RECESSIVE DOPA-RESPONSIVE DYSTONIA Is also known as tyrosine hydroxylase-deficient dopa-responsive dystonia|dyt5b|dopa-responsive dystonia, autosomal recessive|tyrosine hydroxylase deficiency|dystonia, dopa-responsive, autosomal recessive|parkinsonism, infantile, autosomal recessive|autosomal recessive seg

• Generalized hypotonia
• Ataxia
• Ptosis
• Feeding difficulties
• Delayed speech and language development

SOURCES: ORPHANET OMIM MENDELIAN

Thiamine metabolism dysfunction syndrome-2 is an autosomal recessive metabolic disorder characterized by episodic encephalopathy, often triggered by febrile illness, presenting as confusion, seizures, external ophthalmoplegia, dysphagia, and sometimes coma and death. Administration of high doses of biotin, and sometimes thiamine, during these crises results in partial or complete improvement within days. If untreated, encephalopathies can result in permanent dystonia. Brain imaging may show characteristic bilateral lesions of the basal ganglia. It is not known why biotin administration results in clinical improvement, as the molecular basis of the disorder is mutation in a gene encoding a thiamine transporter. However, biotin may increase the gene expression of SLC19A3 (summary by Debs et al., 2010).For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (OMIM ).

BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE Is also known as btbgd|basal ganglia disease, biotin-responsive|biotin-responsive basal ganglia disease|bbgd|encephalopathy, thiamine-responsive

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: ORPHANET MESH OMIM MENDELIAN

Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC) is characterized by slowly progressive spasticity, extrapyramidal movement disorders (dystonia, choreoathetosis and rigidity), cerebellar ataxia, moderate to severe cognitive deficit, and anarthria/dysarthria.

HYPOMYELINATION WITH ATROPHY OF BASAL GANGLIA AND CEREBELLUM Is also known as leukodystrophy, hypomyelinating, with atrophy of the basal ganglia and cerebellum|habc|h-abc

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: MESH ORPHANET OMIM MENDELIAN

X-linked Charcot-Marie-Tooth disease type 1 is a rare, genetic, peripheral sensorimotor neuropathy characterized by an X-linked dominant inheritance pattern and the childhood-onset (within the first decade in males) of progressive, distal, moderate to severe muscle weakness and atrophy in lower extremities and intrinsic hand muscles, pes cavus, bilateral foot drop, reduced or absent tendon reflexes, as well as mild to moderate sensory impairment in lower extremities. Females tend to have milder manifestations or may be asymptomatic. Sensorineural deafness and central nervous system involvement have also been reported.

X-LINKED CHARCOT-MARIE-TOOTH DISEASE TYPE 1 Is also known as cmt2, formerly|cmt1x|charcot-marie-tooth peroneal muscular atrophy, x-linked|cmtx1|cmtx|charcot-marie-tooth neuropathy, x-linked, 1|hereditary motor and sensory neuropathy, x-linked|hmsn, x-linked

• Hearing impairment
• Scoliosis
• Ataxia
• Nystagmus
• Sensorineural hearing impairment

SOURCES: OMIM ORPHANET MENDELIAN

Kufor-Rakeb syndrome (KRS) is a rare genetic neurodegenerative disorder characterized by juvenile Parkinsonism, pyramidal degeneration (dystonia), supranuclear palsy, and cognitive impairment.

KUFOR-RAKEB SYNDROME Is also known as parkinson disease 9, autosomal recessive, juvenile-onset|park9|pallidopyramidal degeneration with supranuclear upgaze paresis and dementia|krppd

• Intellectual disability
• Seizures
• Ataxia
• Nystagmus
• Spasticity

SOURCES: OMIM ORPHANET MENDELIAN

GM1 gangliosidosis type 2 is a clinically variable, infancy or childhood-onset form of GM1 gangliosidosis (see this term) characterized by normal early development and psychomotor regression between seven months and three years of age.

GM1 GANGLIOSIDOSIS TYPE 2 Is also known as late-infantile gm1 gangliosidosis|gangliosidosis, generalized gm1, type ii|juvenile gm1 gangliosidosis|gangliosidosis, generalized gm1, type 2|gangliosidosis, generalized gm1, juvenile type

• Seizures
• Global developmental delay
• Ataxia
• Muscle weakness
• Abnormal facial shape

SOURCES: OMIM ORPHANET MENDELIAN

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary cerebrovascular disorder characterized by mid-adult onset of recurrent subcortical ischemic stroke and cognitive impairment progressing to dementia in addition to migraines with aura and mood disturbances seen in about a third of patients.

CADASIL Is also known as dementia, hereditary multi-infarct type|cadasil|cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy|casil|hereditary multi-infarct dementia

• Seizures
• Hearing impairment
• Ataxia
• Sensorineural hearing impairment
• Muscle weakness

SOURCES: OMIM ORPHANET MENDELIAN

Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance.

CONGENITAL CATARACTS-FACIAL DYSMORPHISM-NEUROPATHY SYNDROME Is also known as ccfdn|cataract, congenital, with facial dysmorphism and neuropathy

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Scoliosis

SOURCES: OMIM MESH ORPHANET MENDELIAN